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Altered microbiome of serum exosomes in patients with acute and chronic cholecystitis

This study aimed to investigate the differences in the microbiota composition of serum exosomes from patients with acute and chronic cholecystitis.

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Saliva‑microbiome‑derived signatures: expected to become a potential biomarker for pulmonary nodules (MCEPN-1)

Oral microbiota imbalance is associated with the progression of various lung diseases, including lung cancer. Pulmonary nodules (PNs) are often considered a critical stage for the early detection of lung cance...

The gut microbiota facilitate their host tolerance to extreme temperatures

Exposure to extreme cold or heat temperature is one leading cause of weather-associated mortality and morbidity in animals. Emerging studies demonstrate that the microbiota residing in guts act as an integral ...

Establishment of an in vitro model of monocyte-like THP-1 cells for trained immunity induced by bacillus Calmette-Guérin

Mycobacteria bloodstream infections are common in immunocompromised people and usually have disastrous consequences. As the primary phagocytes in the bloodstream, monocytes and neutrophils play critical roles ...

The distinct cell physiology of Bradyrhizobium at the population and cellular level

The α-Proteobacteria belonging to Bradyrhizobium genus are microorganisms of extreme slow growth. Despite their extended use as inoculants in soybean production, their physiology remains poorly characterized. In ...

Decoding the role of oxidative stress resistance and alternative carbon substrate assimilation in the mature biofilm growth mode of Candida glabrata

Biofilm formation is viewed as a vital mechanism in C. glabrata pathogenesis. Although, it plays a significant role in virulence but transcriptomic architecture and metabolic pathways governing the biofilm growth...

Occurrence, antimicrobial susceptibility, and resistance genes of Staphylococcus aureus in milk and milk products in the Arsi highlands of Ethiopia

In Ethiopia, milk production and handling practices often lack proper hygiene measures, leading to the potential contamination of milk and milk products with Staphylococcus aureus ( S. aureus ), including methicill...

Based on molecular docking and real-time PCR technology, the two-component system Bae SR was investigated on the mechanism of drug resistance in CRAB

This study aimed to explore the role of the two-component system Bae SR in the mechanism of drug resistance in carbapenem-resistant A. baumannii (CRAB) using molecular docking and real-time polymerase chain react...

Genomic characterization and related functional genes of γ- poly glutamic acid producing Bacillus subtilis

γ- poly glutamic acid (γ-PGA), a high molecular weight polymer, is synthesized by microorganisms and secreted into the extracellular space. Due to its excellent performance, γ-PGA has been widely used in vario...

In silico analysis of intestinal microbial instability and symptomatic markers in mice during the acute phase of severe burns

Severe burns may alter the stability of the intestinal flora and affect the patient’s recovery process. Understanding the characteristics of the gut microbiota in the acute phase of burns and their association...

The effect of white grub ( Maladera Verticalis ) larvae feeding on rhizosphere microbial characterization of aerobic rice ( Oryza sativa L.) in Puer City, Yunnan Province, China

Rhizosphere microorganisms are vital in plants’ growth and development and these beneficial microbes are recruited to the root-zone soil when experiencing various environmental stresses. However, the effect of...

Characterization of genes related to the efflux pump and porin in multidrug-resistant Escherichia coli strains isolated from patients with COVID-19 after secondary infection

Escherichia coli ( E. coli ) is a multidrug resistant opportunistic pathogen that can cause secondary bacterial infections in patients with COVID-19. This study aimed to determine the antimicrobial resistance profi...

Correction: Uncovering the complexity of childhood undernutrition through strain‑level analysis of the gut microbiome

The original article was published in BMC Microbiology 2024 24 :73

Optimization of fermentation conditions and medium components for chrysomycin a production by Streptomyces sp. 891-B6

Chrysomycin A (CA) is a promising antibiotic for treatment of Gram-positive bacterial infections and cancers. In order to enhance CA yield, optimization of fermentation conditions and medium components was car...

Integrative metagenomic analysis reveals distinct gut microbial signatures related to obesity

Obesity is a metabolic disorder closely associated with profound alterations in gut microbial composition. However, the dynamics of species composition and functional changes in the gut microbiome in obesity r...

Ultraviolet C inactivation of Coxiella burnetii for production of a structurally preserved whole cell vaccine antigen

Q fever, a worldwide-occurring zoonotic disease, can cause economic losses for public and veterinary health systems. Vaccines are not yet available worldwide and currently under development. In this regard, it...

Neutrophil extracellular traps formation: effect of Leishmania major promastigotes and salivary gland homogenates of Phlebotomus papatasi in human neutrophil culture

Leishmaniasis as a neglected tropical disease (NTD) is caused by the inoculation of Leishmania parasites via the bite of phlebotomine sand flies. After an infected bite, a series of innate and adaptive immune res...

Assessment of bacterial profile, antimicrobial susceptibility status, and associated factors of isolates among hospitalized patients at Dessie Comprehensive Specialized Hospital, Northeast Ethiopia

Antimicrobial resistant bacteria among hospitalized patients are becoming a major public health threat worldwide, mainly in developing countries. Infections by these multidrug resistant pathogens cause high ra...

A review of emerging health threats from zoonotic New World mammarenaviruses

Despite repeated spillover transmission and their potential to cause significant morbidity and mortality in human hosts, the New World mammarenaviruses remain largely understudied. These viruses are endemic to...

Impact of Limosilactobacillus fermentum probiotic treatment on gut microbiota composition in sahiwal calves with rotavirus diarrhea: A 16S metagenomic analysis study”

Diarrhea poses a major threat to bovine calves leading to mortality and economic losses. Among the causes of calf diarrhea, bovine rotavirus is a major etiological agent and may result in dysbiosis of gut micr...

Genetic characterizations of Cryptosporidium spp. from children with or without diarrhea in Wenzhou, China: high probability of zoonotic transmission

Cryptosporidium is a highly pathogenic parasite responsible for diarrhea in children worldwide. Here, the epidemiological status and genetic characteristics of Cryptosporidium in children with or without diarrhea...

Effect of stress urinary incontinence on vaginal microbial communities

Postpartum women often experience stress urinary incontinence (SUI) and vaginal microbial dysbiosis, which seriously affect women’s physical and mental health. Understanding the relationship between SUI and va...

Hospital distribution, seasonality, time trends and antifungal susceptibility profiles of all Aspergillus species isolated from clinical samples from 2015 to 2022 in a tertiary care hospital

Aspergillus species cause a variety of serious clinical conditions with increasing trend in antifungal resistance. The present study aimed at evaluating hospital epidemiology and antifungal susceptibility of all ...

Comparative analysis of proteomic adaptations in Enterococcus faecalis and Enterococcus faecium after long term bile acid exposure

All gastrointestinal pathogens, including Enterococcus faecalis and Enterococcus faecium , undergo adaptation processes during colonization and infection. In this study, we investigated by data-independent acquisi...

Influence of PhoPQ and PmrAB two component system alternations on colistin resistance from non- mcr colistin resistant clinical E. Coli strains

The current understanding of acquired chromosomal colistin resistance mechanisms in Enterobacterales primarily involves the disruption of the upstream PmrAB and PhoPQ two-component system (TCS) control caused by ...

Staphylococcus aureus foldase PrsA contributes to the folding and secretion of protein A

Staphylococcus aureus secretes a variety of proteins including virulence factors that cause diseases. PrsA, encoded by many Gram-positive bacteria, is a membrane-anchored lipoprotein that functions as a foldase t...

Transcriptional dynamics during Rhodococcus erythropolis infection with phage WC1

Belonging to the Actinobacteria phylum, members of the Rhodococcus genus thrive in soil, water, and even intracellularly. While most species are non-pathogenic, several cause respiratory disease in animals and, m...

A hypervirulent Acinetobacter baumannii strain has robust anti-phagocytosis ability

Acinetobacter baumannii ( A. baumannii ) is associated with both hospital-acquired infections (HAP) and community-acquired pneumonia (CAP). In this study, we present a novel CAP-associated A. baumannii (CAP-AB) str...

Restoration of gut dysbiosis through Clostridium butyricum and magnesium possibly balance blood glucose levels: an experimental study

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by an elevated level of blood glucose due to the absence of insulin secretion, ineffectiveness, or lack of uptake of secreted insulin in the...

Bacillus subtilis SOM8 isolated from sesame oil meal for potential probiotic application in inhibiting human enteropathogens

While particular strains within the Bacillus species, such as Bacillus subtilis , have been commercially utilised as probiotics, it is critical to implement screening assays and evaluate the safety to identify pot...

Promiscuous, persistent and problematic: insights into current enterococcal genomics to guide therapeutic strategy

Vancomycin-resistant enterococci (VRE) are major opportunistic pathogens and the causative agents of serious diseases, such as urinary tract infections and endocarditis. VRE strains mainly include species of Ente...

Comparison of integron mediated antimicrobial resistance in clinical isolates of Escherichia coli from urinary and bacteremic sources

Antimicrobial resistance (AMR) is a global threat driven mainly by horizontal gene transfer (HGT) mechanisms through mobile genetic elements (MGEs) including integrons. The variable region (VR) of an integron ...

Structure predictions and functional insights into Amidase_3 domain containing N -acetylmuramyl-L-alanine amidases from Deinococcus indicus DR1

N -acetylmuramyl-L-alanine amidases are cell wall modifying enzymes that cleave the amide bond between the sugar residues and stem peptide in peptidoglycan. Amidases play a vital role in septal cell wall cleavag.....

Profile of non-tuberculous mycobacteria amongst tuberculosis presumptive people in Cameroon

Cameroon is a tuberculosis (TB) burden country with a 12% positivity among TB presumptive cases. Of the presumptive cases with a negative TB test, some are infected with Non-tuberculous Mycobacteria (NTM). How...

In vitro investigation of relationship between quorum-sensing system genes, biofilm forming ability, and drug resistance in clinical isolates of Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic pathogen in the health-care systems and one of the primary causative agents with high mortality in hospitalized patients, particularly immunocompromised. The limitation ...

Relationship between heart failure and intestinal inflammation in infants with congenital heart disease

The association between heart failure (HF) and intestinal inflammation caused by a disturbed intestinal microbiota in infants with congenital heart disease (CHD) was investigated.

Clostridium butyricum inhibits the inflammation in children with primary nephrotic syndrome by regulating Th17/Tregs balance via gut-kidney axis

Primary nephrotic syndrome (PNS) is a common glomerular disease in children. Clostridium butyricum ( C. butyricum), a probiotic producing butyric acid, exerts effective in regulating inflammation. This study was d...

Human-derived bacterial strains mitigate colitis via modulating gut microbiota and repairing intestinal barrier function in mice

Unbalanced gut microbiota is considered as a pivotal etiological factor in colitis. Nevertheless, the precise influence of the endogenous gut microbiota composition on the therapeutic efficacy of probiotics in...

In vitro and in silico studies of enterobactin-inspired Ciprofloxacin and Fosfomycin first generation conjugates on the antibiotic resistant E. coli OQ866153

The emergence of antimicrobial resistance in bacterial pathogens is a growing concern worldwide due to its impact on the treatment of bacterial infections. The "Trojan Horse" strategy has been proposed as a po...

HPV-associated cervicovaginal microbiome and host metabolome characteristics

Cervicovaginal microbiome plays an important role in the persistence of HPV infection and subsequent disease development. However, cervicovaginal microbiota varied cross populations with different habits and r...

Transcriptomic and physiological analyses of Trichoderma citrinoviride HT-1 assisted phytoremediation of Cd contaminated water by Phragmites australis

Plant growth promoting microbe assisted phytoremediation is considered a more effective approach to rehabilitation than the single use of plants, but underlying mechanism is still unclear. In this study, we co...

Long-term push–pull cropping system shifts soil and maize-root microbiome diversity paving way to resilient farming system

The soil biota consists of a complex assembly of microbial communities and other organisms that vary significantly across farming systems, impacting soil health and plant productivity. Despite its importance, ...

Pretreatment with an antibiotics cocktail enhances the protective effect of probiotics by regulating SCFA metabolism and Th1/Th2/Th17 cell immune responses

Probiotics are a potentially effective therapy for inflammatory bowel disease (IBD); IBD is linked to impaired gut microbiota and intestinal immunity. However, the utilization of an antibiotic cocktail (Abx) p...

High-throughput sequencing reveals differences in microbial community structure and diversity in the conjunctival tissue of healthy and type 2 diabetic mice

To investigate the differences in bacterial and fungal community structure and diversity in conjunctival tissue of healthy and diabetic mice.

High prevalence of ST5-SCC mec II-t311 clone of methicillin-resistant Staphylococcus aureus isolated from bloodstream infections in East China

Methicillin-resistant Staphylococcus aureus (MRSA) is a challenging global health threat, resulting in significant morbidity and mortality worldwide. This study aims to determine the molecular characteristics and...

Characteristics of the oral and gastric microbiome in patients with early-stage intramucosal esophageal squamous cell carcinoma

Oral microbiome dysbacteriosis has been reported to be associated with the pathogenesis of advanced esophageal cancer. However, few studies investigated the potential role of oral and gastric microbiota in ear...

The potential role of Listeria monocytogenes in promoting colorectal adenocarcinoma tumorigenic process

Listeria monocytogenes is a foodborne pathogen, which can cause a severe illness, especially in people with a weakened immune system or comorbidities. The interactions between host and pathogens and between patho...

Evaluation of clinical characteristics and risk factors associated with Chlamydia psittaci infection based on metagenomic next-generation sequencing

Psittacosis is a zoonosis caused by Chlamydia psittaci , the clinical manifestations of Psittacosis range from mild illness to fulminant severe pneumonia with multiple organ failure. This study aimed to evaluate t...

Characterization of the broad-spectrum antibacterial activity of bacteriocin-like inhibitory substance-producing probiotics isolated from fermented foods

Antimicrobial peptides, such as bacteriocin, produced by probiotics have become a promising novel class of therapeutic agents for treating infectious diseases. Selected lactic acid bacteria (LAB) isolated from...

Metagenomic gut microbiome analysis of Japanese patients with multiple chemical sensitivity/idiopathic environmental intolerance

Although the pathology of multiple chemical sensitivity (MCS) is unknown, the central nervous system is reportedly involved. The gut microbiota is important in modifying central nervous system diseases. Howeve...

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Microbiology

Viral Genetics Confirms What On-the-Ground Activists Knew Early in the Mpox Outbreak

Molecular biology could have changed the mpox epidemic—and could stop future outbreaks

Joseph Osmundson

Cannibal Cells Inspire Cancer Treatment Improvement

Giving cells an appetite for cancer could enhance treatments

Kate Graham-Shaw

Is Raw-Milk Cheese Safe to Eat?

Recent bacterial outbreaks from consuming cheese made from unpasteurized milk, or “raw milk,” raise questions about the safety of eating these artisanal products

Riis Williams

Many Pregnancy Losses Are Caused by Errors in Cell Division

Odd cell divisions could help explain why even young, healthy couples might struggle to get pregnant

Gina Jiménez

'Microbiome of Death' Uncovered on Decomposing Corpses Could Aid Forensics

Microbes that lurk in decomposing human corpses could help forensic detectives establish a person's time of death

Christoph Schwaiger, LiveScience

Weird ‘Obelisks’ Found in Human Gut May be Virus-Like Entities

Rod-shaped fragments of RNA called “obelisks” were discovered in gut and mouth bacteria for the first time

Joanna Thompson

Semen Has Its Own Microbiome—And It Might Influence Fertility

Recent research found a species of bacteria living in semen that’s associated with infertility and has links to the vaginal microbiome

Andrew Chapman

Bacteria Make Decisions Based on Generational Memories

Bacteria choose to swarm based on what happened to their great-grandparents

Allison Parshall

Your Body Has Its Own Built-In Ozempic

Popular weight-loss and diabetes drugs, such as Ozempic and Wegovy, target metabolic pathways that gut microbes and food molecules already play a key role in regulating

Christopher Damman, The Conversation US

See Your Body’s Cells in Size and Number

The larger a cell type is, the rarer it is in the body—and vice versa—a new study shows

Clara Moskowitz, Jen Christiansen, Ni-ka Ford

Subterranean ‘Microbial Dark Matter’ Reveals a Strange Dichotomy

The genes of microbes living as deep as 1.5 kilometers below the surface reveal a split between minimalist and maximalist lifestyles

Stephanie Pappas

The Vaginal Microbiome May Affect Health More than We Thought

A recent study finds varying combinations of microbes in the vaginal microbiome may influence health outcomes such as risk of sexually transmitted disease and preterm birth

Lori Youmshajekian

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Six Key Topics in Microbiology: 2019

Read an essential collection of papers showcasing high-quality content from across the five FEMS Journals, which together provide an overview of current research trends in microbiology. Follow the topic area links below for access to articles:

• Antimicrobial Resistance

Environmental Microbiology

Pathogenicity & virulence, biotechnology & synthetic biology, microbiomes, food microbiology, antimicrobial resistance.

Effects of sample preservation and DNA extraction on enumeration of antibiotic resistance genes in wastewater An-Dong Li, Jacob W Metch, Yulin Wang, Emily Garner, An Ni Zhang, Maria V Riquelme, Peter J Vikesland, Amy Pruden, Tong Zhang FEMS Microbilogy Ecology , DOI: 10.1093/femsec/fix189 First published online: 1 February 2018

Occurrence and abundance of antibiotic resistance genes in agricultural soil receiving dairy manure Chad W McKinney, Robert S Dungan, Amber Moore, April B Leytem FEMS Microbiology Ecology , DOI: 10.1093/femsec/fiy010; First published online: 1 March 2018

Environmental factors influencing the development and spread of antibiotic resistance Johan Bengtsson-Palme, Erik Kristiansson, D G Joakim Larsson FEMS Microbiology Reviews , DOI: 10.1093/femsre/fux053 First published online: 01 January 2018

Comparative genomic and transcriptomic analyses unveil novel features of azole resistnce and adaptation to the human host in Candida glabrata Sara Barbosa Salazar, Can Wang, Martin Münsterkötter, Michiyo Okamoto, Azusa Takahashi-Nakaguchi, Hiroji Chibana, Maria Manuel Lopes, Ulrich Güldener, Geraldine Butler, Nuno Pereira Mira FEMS Yeast Research , DOI: 10.1093/femsyr/fox079 First published online: 01 February 2018

How proteases from Enterococcus faecalis contribute to its resistance to short a-helical antimicrobial peptides Ondrej Nešuta, Miloš Budešínský, Romana Hadravová, Lenka Monincová, Jana Humpolicková, Václav Cerovský FEMS Pathogens and Disease , DOI: 10.1093/femspd/ftx091 First published online: 29 September 2017

Ice algal bloom development on the surface of the Greenland Ice Sheet C J Williamson, A M Anesio, J Cook, A Tedstone, E Poniecka, A Holland, D Fagan, M Tranter, M L Yallop FEMS Microbiology Ecology DOI: 10.1093/femsec/fiy025 First published online: 01 March 2018

Investigation of viable taxa in the deep terrestrial biosphere suggests high rates of nutrient recycling Margarita Lopez-Fernandez, Elias Broman, Stephanie Turner, Xiaofen Wu, Stefan Bertilsson, Mark Dopson FEMS Microbiology Ecology , DOI: 10.1093/femsec/fiy121 First published online: 01 August 2018

Soil Protists: a fertile frontier in soil biology research Stefan Geisen, Edward A D Mitchell, Sina Adl, Michael Bonkowski, Micah Dunthorn, Flemming Ekelund, Leonardo D Fernández, Alexandre Jousset, Valentyna Krashevska, David Singer, Frederick W Spiegel, Julia Walochnik, Enrique Lara FEMS Microbiology Reviews , DOI: 10.1093/femsre/fuy006 First published online: 01 May 2018

Vector-borne diseases and climate change: a European perspective Jan C Semenza, Jonathan E Suk FEMS Microbiology Letters , DOI: 10.1093/femsle/fnx244 First published online: 01 January 2018

Beyond nitrogen metabolism: nitric oxide, cyclic-di- GMP and bacterial biofilms Serena Rinaldo, Giorgio Giardina, Federico Mantoni, Alessio Paone, Francesca Cutruzzolàr FEMS Microbiology Letters , DOI: 10.1093/femsle/fny029 First published online: 01 March 2018

Bacterial-fungal interactions: ecology, mechanisms and challenges Aurélie Deveau, Gregory Bonito, Jessie Uehling, Mathieu Paoletti, Matthias Becker, Saskia Bindschedler, Stéphane Hacquard, Vincent Hervé, Jessy Labbé, Olga A Lastovetsky, Sophie Mieszkin, Larry J Millet, Balázs Vajna, Pilar Junier, Paola Bonfante, Bastiaan P Krom, Stefan Olsson, Jan Dirk van Elsas, Lukas Y Wick FEMS Microbiology Reviews , DOI: 10.1093/femsre/fuy008 First published online: 01 May 2018

The human cytomegalovirus terminase complex as an antiviral target: a close-up view G Ligat, R Cazal, S Hantz, S Alain; FEMS Microbiology Reviews , DOI: 10.1093/femsre/fuy004 First published online: 01 March 2018

Molecular variability and genetic structure of white spot syndrome virus strains from northwest Mexico based on the analysis of genomes Delia Patricia Parrilla-Taylor, Norberto Vibanco-Pérez, Maria de Jesús Durán-Avelar, Bruno Gomez- Gil, Raúl Llera-Herrera, Ricardo Vázquez-Juárez FEMS Microbiology Letters , DOI: 10.1093/femsle/fny216 First published online: 01 October 2018

The first known virus isolates from Antarctic sea ice have complex infection patterns Anne-Mari Luhtanen, Eeva Eronen-Rasimus, Hanna M Oksanen, Jean-Louis Tison, Bruno Delille, Gerhard S Dieckmann, Janne-Markus Rintala, Dennis H Bamford FEMS Microbiology Ecology , DOI: 10.1093/femsec/fiy028 First published online: 1 April 2018

Host-pathogen redox dynamics modulate Mycobacterium tuberculosis pathogenesis Hayden T Pacl, Vineel P Reddy, Vikram Saini, Krishna C Chinta, Adrie J C Steyn FEMS Pathogens and Disease , DOI: 10.1093/femspd/fty036 First published online: 01 July 2018

The CRISPR-Cas system in Enterobacteriaceae Liliana Medina-Aparicio, Sonia Dávila, Javier E Rebollar-Flores, Edmundo Calva, Ismael Hernández- Lucas FEMS Pathogens and Disease , DOI: 10.1093/femspd/fty002 First published online: 01 February 2018

Mycobacterial biomaterials and resources for researchers Manzour Hernando Hazbón, Leen Rigouts, Marco Schito, Matthew Ezewudo, Takuji Kudo, Takashi Itoh, Moriya Ohkuma, Katalin Kiss, Linhuan Wu, Juncai Ma, Moriyuki Hamada, Michael Strong, Max Salfinger ,Charles L Daley, Jerry A Nick, Jung-Sook Lee, Nalin Rastogi, David Couvin, Raquel Hurtado-Ortiz, Chantal Bizet, Anita Suresh, Timothy Rodwell, Audrey Albertini, Karen A Lacourciere, Ana Deheer- Graham, Sarah Alexander, Julie E Russell, Rebecca Bradford, Marco A Riojas FEMS Pathogens and Disease , DOI: 10.1093/femspd/fty042 First published online: 01 June 2018

Yeast 2.0- connecting the dots in the construction of the world's first functional synthetic eukaryotic genome I S Pretorius, J D Boeke FEMS Yeast Research , DOI: 10.1093/femsyr/foy032 First published online: 01 June 2018

Laboratory evolution for forced glucose-xylose co-consumption enables identification of mutations that improve mixed-sugar fermentation by xylose-fermenting Saccharomyces cerevisiae Ioannis Papapetridis, Maarten D Verhoeven, Sanne J Wiersma, Maaike Goudriaan, Antonius J A van Maris, Jack T Pronk FEMS Yeast Research , DOI: 10.1093/femsyr/foy056 First published online:01 September 2018

State of the art in eukaryotic nitrogenase engineering Stefan Burén, Luis M Rubio FEMS Microbiology Letters , DOI: 10.1093/femsle/fnx274 First published online: 01 January 2018

Whole-genome sequencing based characterization of antimicrobial resistance in Enterococcus Gregory H Tyson, Jonathan L Sabo, Crystal Rice-Trujillo, Jacqueline Hernandez, Patrick F McDermott FEMS Pathogens and Disease , DOI: 10.1093/femspd/fty018 First published online: 01 March 2018

Biofilm growth and control in cooling water industrial systems F Di Pippo, L Di Gregorio, R Congestri, V Tandoi, S Rossetti FEMS Microbiology Ecology , DOI: 10.1093/femsec/fiy044 First published online: 01 May 2018

Novel sequencing technologies to support industrial biotechnology Adalberto Costessi, Bartholomeus van den Bogert, Ali May, Emiel Ver Loren van Themaat, Johannes A Roubos, Marc A B Kolkman, Derek Butler, Walter Pirovano FEMS Microbiology Letters , DOI: 10.1093/femsle/fny103 First published online: 01 August 2018

Influenza A virus subtype H9N2 infection disrupts the composition of intestinal microbiota of chickens Alexander Yitbarek, J Scott Weese, Tamiru Negash Alkie, John Parkinson, Shayan Sharif FEMS Microbiology Ecology , DOI: 10.1093/femsec/fix165 First published online: 01 January 2018

Pathogens, microbiome and the host: emergence of the ecological Koch's postulates Pascale Vonaesch, Mark Anderson, Philippe J Sansonetti FEMS Microbiology Reviews , DOI: 10.1093/femsre/fuy003 First published online: 09 January 2018

Talk to your gut: the oral-gut microbiome axis and its immunomodulatory role in the etiology of rheumatoid arthritis Marines du Teil Espina, Giorgio Gabarrini, Hermie J M Harmsen, Johanna Westra, Arie Jan van Winkelhoff, Jan Maarten van Dijl FEMS Microbiology Reviews , DOI: 10.1093/femsre/fuy035 First published online: 01 January 2019

Shift of hindgut microbiota and microbial short chain fatty acids profiles in dairy calves from birth to pre-weaning Yang Song, Nilusha Malmuthuge, Michael A Steele, Le Luo Guan FEMS Microbiology Ecology , DOI: 10.1093/femsec/fix179 First published online: 01 March 2018

The Smallest Intestine (TSI)- a low volume in vitro model of the small intenstine with increased throughput T Cieplak, M Wiese, S Nielsen, T Van de Wiele, F van den Berg, D S Nielsen FEMS Microbiology Letters , DOI: 10.1093/femsle/fny231 First published online: 01 November 2018

Saccharomyces cerevisiae variety diastaticus friend or foe? - spoilage potential and brewing ability of different Saccharomyces cerevisiae variety diastaticus yeast isolates by genetic, phenotypic and physiological characterization Tim Meier-Dörnberg, Oliver Ingo Kory, Fritz Jacob, Maximilian Michel, Mathias Hutzler FEMS Yeast Research , DOI: 10.1093/femsyr/foy023 First published online: 01 June 2018

Trans-regulation and localization of orthologous maltose transporters in the interspecies lager yeast hybrid Virve Vidgren, Brian Gibson FEMS Yeast Research , DOI: 10.1093/femsyr/foy065 First published online: 01 September 2018

Fermentation performances and aroma production of non-conventional wine yeasts are influenced by nitrogen preferences Stéphanie Rollero, Audrey Bloem, Anne Ortiz-Julien, Carole Camarasa, Benoit Divol FEMS Yeast Research , DOI: 10.1093/femsyr/foy055 First published online: 01 August 2018

Community-led comparative genomic and phenotypic analysis of the aquaculture pathogen Pseudomonas baetica a390T sequenced by Ion semiconductor and Nanopore technologies Ainsley Beaton, Cédric Lood, Edward Cunningham-Oakes, Alison MacFadyen, Alex J Mullins, Walid El Bestawy, João Botelho, Sylvie Chevalier, Shannon Coleman, Chloe Dalzell, Stephen K Dolan, Alberto Faccenda, Maarten G K Ghequire, Steven Higgins, Alexander Kutschera, Jordan Murray, Martha Redway, Talal Salih, Ana C da Silva, Brian A Smith, Nathan Smits, Ryan Thomson, Stuart Woodcock, Martin Welch, Pierre Cornelis, Rob Lavigne, Vera van Noort, Nicholas P Tucker FEMS Microbiology Letters , DOI: 10.1093/femsle/fny069 First published online: 01 May 2018

Antibiotic resistance phenotypes and virulence-associated genes in Escherichia coli isolated from animals and animal food products in Tunisia Souhir Badi, Paola Cremonesi, Mohamed Salah Abbassi, Chourouk Ibrahim, Majdi Snoussi, Giulia Bignoli, Mario Luini, Bianca Castiglioni, Abdennaceur Hassen FEMS Microbiology Letters , DOI: 10.1093/femsle/fny088 First published online: 01 May 2018

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Microbiology

• Publishes experimental and theoretical articles, critical reviews, and short communications.
• The target audience is specialists at research institutions and medical workers.
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• Nikolai.V Pimenov

Latest issue

Volume 93, Issue 2

Proceedings of the IV Russian Microbiological Congress, 2023

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Drug resistance of different mycobacterium tuberculosis genotypes in the omsk oblast of russia.

• A. A. Vyazovaya
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Application of Flow Cytometry for Viability Assay of Mutants for Translation Termination Factors in the Yeast Saccharomyces cerevisiae

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Role of Copper Ions in Resistance of Modern Polymer Composite Materials to Fungal Damage

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Destruction of Biofilms of Gram-Positive and Gram-Negative Bacteria by Serine Protease PAPC from Aspergillus ochraceus

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Alkaline Phosphatase Activity and Phosphatase-Active Bacteria in Lake Baikal Water Column and Major Tributaries

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The gut microbiome in human health and disease—Where are we and where are we going? A bibliometric analysis

Associated data.

The original contributions presented in the study are included in the article/ Supplementary material , further inquiries can be directed to the corresponding author.

There are trillions of microbiota in our intestinal tract, and they play a significant role in health and disease via interacting with the host in metabolic, immune, neural, and endocrine pathways. Over the past decades, numerous studies have been published in the field of gut microbiome and disease. Although there are narrative reviews of gut microbiome and certain diseases, the whole field is lack of systematic and quantitative analysis. Therefore, we outline research status of the gut microbiome and disease, and present insights into developments and characteristics of this field to provide a holistic grasp and future research directions.

An advanced search was carried out in the Web of Science Core Collection (WoSCC), basing on the term “gut microbiome” and its synonyms. The current status and developing trends of this scientific domain were evaluated by bibliometric methodology. CiteSpace was used to perform collaboration network analysis, co-citation analysis and citation burst detection.

A total of 29,870 articles and 13,311 reviews were retrieved from the database, which involve 42,900 keywords, 176 countries/regions, 19,065 institutions, 147,225 authors and 4,251 journals. The gut microbiome and disease research is active and has received increasing attention. Co-cited reference analysis revealed the landmark articles in the field. The United States had the largest number of publications and close cooperation with other countries. The current research mainly focuses on gastrointestinal diseases, such as inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), while extra-intestinal diseases are also rising, such as obesity, diabetes, cardiovascular disease, Alzheimer’s disease, Parkinson’s disease. Omics technologies, fecal microbiota transplantation (FMT) and metabolites linked to mechanism would be more concerned in the future.

The gut microbiome and disease has been a booming field of research, and the trend is expected to continue. Overall, this research field shows a multitude of challenges and great opportunities.

Introduction

The human gut microbiota originated from colonization by environmental microbes during birth, and live in symbiosis with the host throughout life ( Koenig et al., 2011 ; Kundu et al., 2017 ). The inoculum source usually and mainly is the mother’s vaginal and fecal microbiomes ( Koenig et al., 2011 ). Human microbiota carried diverse set of genomes, and is considered as human second genome ( Grice and Segre, 2012 ). While the microbes that reside in our gut account for the vast majority, present more than 1,000 species ( Almeida et al., 2019 ), and the number of microorganisms is estimated up to trillions ( Sender et al., 2016 ). These abundant and diverse gut microbes constitute a dynamic and complex ecosystem and perform various functions that are essential for the human host ( Heintz-Buschart and Wilmes, 2018 ). On the one hand, there are competition and cooperation within these microbial consortia ( Coyte and Rakoff-Nahoum, 2019 ), on the other hand, they also interact with the host in multiple aspects, including digestion and metabolism ( Krautkramer et al., 2021 ), immune system ( Rooks and Garrett, 2016 ) and unconscious system ( Dinan and Cryan, 2017 ). Hence, the gut microbiome directly or indirectly impacts the host’s health.

It should be noted that the concept that our resident microbial communities make essential contributions to the host’s physiology and health can date back to Louis Pasteur (1822–1895; Stappenbeck et al., 2002 ). Indeed, the gut microbiome has been associated with various diseases and conditions in the past decades, such as IBD ( Morgan et al., 2012 ), obesity ( Fei and Zhao, 2013 ), diabetes ( Lau et al., 2021 ), Parkinson’s disease ( Wallen et al., 2021 ) and cancer ( Gopalakrishnan et al., 2018 ). Meanwhile, the gut microbiome shows great promise for disease diagnosis, i.e., as microbial biomarkers with operational taxonomic units (OTUs), taxa and metabolite ( Wu et al., 2021 ); and for disease therapy by manipulation of the gut microbiome, such as dietary interventions, microbial supplements and FMT ( Durack and Lynch, 2018 ).

The role of the gut microbiome in human health and disease has received increasing attention over the last 20 years, and the trend is expected to continue. At present, some fundamental problems need to be addressed in this field. For example, the taxa, genome, functions and cultivation of microbial dark matter ( Pasolli et al., 2019 ; Jiao et al., 2021 ). Moreover, although many studies have shed light on gut microbiome in health and disease, and established correlations with various diseases in both experimental animals and humans, the causal relationship and molecular mechanisms remain unclear in the most studies. Besides, the application strategies and safety problems in gut microbiome interventions need to be taken into account ( Swann et al., 2020 ). With the biotechnological and computational advancement in this field, more and further explorations will certainly be conducted.

Currently, the volume of scientific literatures about the gut microbiome and disease presents exponential growth. Although there are narrative reviews of gut microbiome and a specific disease, the entire research filed of the gut microbiome and disease is still lack of systematic and quantitative analysis. It is essential to outline this research domain to provide relevant scholars a ready and holistic grasp. Bibliometrics is a multidisciplinary discipline of quantitative analysis of all knowledge carriers by mathematical and statistical methods ( Yu et al., 2018 ). The number and citations of academic publications can reflect the knowledge structure and development features of a scientific domain. Bibliometric analysis is beneficial for identifying and mapping the cumulative scientific knowledge and evolutionary nuances of scientific fields ( Donthu et al., 2021 ). Bibliometrics has been widely used in many other fields, such as economic management, information science, energy and environment ( Yu et al., 2020b ). Therefore, we profile the research landscape of gut microbiome and disease with bibliometric methodology, to provide historical context and detect hot topics and emerging areas in this field. Furthermore, future evolutionary paths and challenges in this field are discussed.

Materials and methods

Data source and search strategy.

Data were retrieved by an advanced search from the WoSCC of Clarivate Analytics, 1 a curated collection of high-quality academic material on the Web of Science™ platform generally used for literature search, journal selection, research evaluation and bibliometric analysis ( Li et al., 2018 ). To avoid bias due to daily updates of the database, document retrieval and export were performed within a single day (May 1, 2022). In order to include as far as possible relevant publications, synonyms for the gut microbiota and disease were included in the search strategy, and the boolean search was set to TS = [(gut* OR intestin* OR gastrointestin* OR gastro-intestin*) AND (microbiota OR microbiome OR flora OR microflora OR bacteria OR microbe* OR microorganism*)] AND TS = (disease*). The time span of publications was set as 1985-01-01 to 2021-12-31. The full record and cited references of the retrieved documents were saved for further analysis. The workflow of the study was presented in Supplementary Figure 1 .

Bibliometric analysis and data visualization

Given that original research is considered as primary literature and presents new knowledge to a certain research area, the “Articles” type of documents was used to evaluate the trends and hotspots of the gut microbiome and disease research. Citespace ( Chen et al., 2012 ; v5.8.R3) was used to analyze reference co-citation, keyword co-occurrence, keywords burst and cooperation relationships among countries, institutions and authors. The Gephi ( Bastian et al., 2009 ; v.0.9.2) was used to construct network graphs.

Research trend of gut microbiome in human health and disease

The increase of publications number and subject categories.

A total of 45,207 academic publications were retrieved from WoSCC, and publication years were distributed from 1996 to 2021. Among these publications, articles account for 66.074% (29,870 records), reviews account for 29.445% (13,311 records), other document types and their percentages see Supplementary Table 1 . The overall output of publications has increased approximately exponentially for the last two decades ( Figure 1A ). Most of the studies were reported in the recent 15 years (n = 27,558, 92.260%). A turning point can be observed around 2007 ( Figures 1B , ​ ,C), C ), since that, the number of publications has been rising drastically. This is partially because of the invention of next-generation sequencing technologies. Other important reasons are the completion of the Human Genome Project (HGP) the launch of the Human Microbiome Project (HMP) and the Metagenomics of The Human Intestinal Tract (MetaHIT). The number of articles supported by fund(s), funding agencies, and funding projects has also been increasing for 26 years ( Figures 1C , ​ ,D), D ), and the percentage of articles supported by fund(s) has been up to 80% in recent 5 years. These results reveal that the gut microbiome and disease research is active and has received increasing attention.

The trend of publications and funding in the research field of gut microbiome and disease. (A) The cumulative number of publications in each year and their exponential regressions. (B) The year-on-year growth rate of publications. (C) The number and percentage of funded articles. (D) The number of funding agencies and projects each year.

A variety of web of science categories (174/254) are involved in these published articles (29,870), and the number was gradually ascending to 130 in 2021 ( Supplementary Figure 2A ), which suggests that the scientific field presents interdisciplinary characteristics ( Supplementary Figures 3 , 4A – D ). The top 10 subject categories are Microbiology, Immunology, Multidisciplinary Sciences, Gastroenterology & Hepatology, Biochemistry & Molecular Biology, Nutrition & Dietetics, Food Science & Technology, Pharmacology & Pharmacy and Biotechnology & Applied Microbiology, and the co-occurrence network of subject categories in the recent 5 years is shown in Supplementary Figure 2B . This research area shows tight relationships with medicine, immunology and nutrition besides microbiology ( Supplementary Figures 2C , 5 ). There is remarkable growth in the number of articles related to cancer and the nerve system every year ( Supplementary Figures 2D , 5 ).

The shift of research topics

The top 200 out of 33,664 keywords by frequency in 1996–2021 were used to construct heatmaps. These keywords were classified into nine categories, including “Definition,” “Technology,” “Experimental subjects” ( Supplementary Figure 6 ), “Diseases/Conditions,” “Immunity,” “Mechanism,” “Metabolism,” “Intervention,” and “Microbes” ( Figure 2 ). Description about this scientific area shifts gradually from “microflora” to “microbiota” and “microbiome” ( Supplementary Figure 6A ). A technological transition from PCR to sequencing and omics technologies is detected ( Supplementary Figure 6B ). The primary research subjects include “child,” “infant,” “pregnancy,” and “mice” ( Supplementary Figure 6C ).

Heatmap of the top 200 keywords by frequency from articles published in 1998–2021. (A) The keywords related to “Diseases/Conditions.” (B) The keywords related to “Immunity,” “Mechanism,” and “Metabolism.” (C) The keywords related to “Intervention.” (D) The keywords related to “Microbes.”

Intestinal diseases have higher keywords frequency than others ( Figure 2A ). Additionally, most intestinal diseases cover almost the whole period in this research area, and part of them remain hot topics with high keywords frequency, such as “Inflammatory bowel disease,” “ulcerative colitis,” and “Crohn’s disease.” This is easy to understand, considering that the intestines provide a natural habitat for these microorganisms and exchange substances with them. While extra-intestinal diseases draw scientists’ attention in the later years, such as obesity, diabetes, Alzheimer’s disease, Parkinson’s disease, cardiovascular disease, hypertension and depression. Due to the COVID-19 pandemic, the connection between it and the gut microbiota was also established ( Figure 2A ). Metabolism-related topics with the highest focus are short chain fatty acids (SCFA), butyrate, bile acid and trimethylamine N-oxide (TMAO). Hot topics related to immunity are cytokines, innate immunity and intestinal barrier ( Figure 2B ). Probiotics, antibiotics, diet and prebiotics are popular topics in invention of gut microbiome, while FMT and high fat diet are emerging topic ( Figure 2C ). In this field, the primary concern of microbes are probiotics and intestinal pathogens ( Figure 2D ). Supplementary Figure 7 shows the changing trend in the top 15 keywords over time.

Keywords burst means the sudden increase of keywords frequency in a specific period, which involves two attributes—burst strength and duration. A total of 726 keywords were detected as burst keywords. These keywords were also classified into seven categories, i.e., “Definition,” “Technology” ( Supplementary Figure 8 ), “Diseases/Conditions,” “Metabolism,” “Immunity,” “Mechanism,” and “Intervention” ( Figure 3 ). Description and technological shift in the development of the field are also observed ( Supplementary Figure 8 ). 16S rRNA sequencing has become the most useful and active technique to decipher the diversity and abundance of the microbiome.

Keywords with strongest bursts from 1998 to 2021. (A) The keywords related to “Diseases/Conditions.” (B) The keywords related to “Immunity,” “Mechanism,” and “Metabolism.” (C) The keywords related to “Intervention.” Asterisk (*) indicate the origin words missed single quotation marks or blank and has been corrected. The red bars indicate burst duration and strength.

The top 5 burst keywords related to disease with the highest burst strength are “Crohn’s disease,” “dysbiosis,” “atopic disease,” “ulcerative colitis,” and “Parkinson’s disease.” “Intestinal inflammation” has the longest burst duration (1998–2018) followed by “Crohn’s disease” and “diarrhea.” Overall burst keywords related to intestinal disease covered the early and middle period (−2013) such as “enterocolitis,” “Crohn’s disease,” and “diarrhea”; while extra-intestinal diseases take up the later period (2014–2021) such as “obesity,” “cardiovascular disease,” “Alzheimer’s disease,” “anxiety,” “Parkinson’s disease,” “dementia,” “depression,” “hypertension,” and “type 2 diabetes mellitus” ( Figure 3A ). The burst keywords involving “Immunity,” “Mechanism,” and “Metabolism” are presented in Figure 3B . Among them “colonic fermentation,” “bile,” and “lipopolysaccharide” burst at early period. On the contrary “SCFA,” “TMAO,” and “phosphatidylcholine” are detected as burst keywords in recent years. As for the intervention of the gut microbiome “FMT,” “fiber,” “dietary supplementation” and high-fat diet are identified as burst keywords over the last several years ( Figure 3C ).

Knowledge map of gut microbiome and disease

Co-cited references are those articles cited together by other articles, and thus, can be regarded as the knowledge basis of a certain field. The knowledge map of the co-occurrence references reveals the developments and characteristics of this field ( Figure 4 ). The nodes size, i.e., co-citations times, is generally larger than the previous one since 2007. The largest component of the co-citation network is divided into 41 clusters (size >1), which show the diversity of research topics. The top 10 articles by cited times and co-cited times are listed in Supplementary Tables 2 , 3 , respectively. A total of 2,115 articles are detected as citation bust, the highest strength is 185.33, and the longest duration is 9 years. Articles with high centrality are often considered as critical points or turning points in a field, and the top 10 articles are marked in Figure 4 and listed in Supplementary Table 4 ; their publication time range from 2002 to 2010.

The top 5 largest components of co-citation network on the gut microbiome and disease between 1997 and 2021. Each node represents a cited article, and the size reflects the number of co-citations, and the edges denote the co-cited relationships among articles.

Present status of scientific collaboration and journal analysis

Country cooperation.

The data of publications in recent 5 years is utilized to evaluate the present cooperative status in the research filed of the gut microbiome and disease. A total of 18,049 articles were from 157 countries/regions in 2017–2021; the top 10 countries in terms of publications and centrality are shown in Supplementary Table 5 . More than half of the publications were produced by the United States ( n  = 5,323) and China ( n  = 5,253), accounting for 29.5 and 29.1% of the total, respectively, while every other country contributed less than 6% of the total. Figure 5A shows the international research collaborations among the leading countries in papers output in this field. A higher centrality indicates that more information is passed through the node, which implies the importance of nodes in the network. The United States has the highest centrality value (0.52), followed by England (0.31) and Germany (0.14). Besides, the United States is the most active nation with the largest number of publications in this research filed. Although China’s publications amount is commensurate with the United States, it lagged behind in collaborations with other countries. Japan and India also had poor performance in collaborations among these top 15 countries.

The cooperation network in different levels from 2017 to 2021. (A) The cooperation network of the top 15 most productive countries. The colored rings in the node represent publications amount in different years. The lines’ thickness and color indicate the strength of cooperation relationships and the year of first cooperation, respectively. (B) The largest component of cooperation network of institutions. The top 10 institutions in the number of publications are colored. (C) The largest component of author cooperation network. The top 10 authors in the number of publications are colored. The nodes’ size and the thickness of the lines positively correlated to the production of papers and the strength of cooperation relationships, respectively.

Institution cooperation

There are 559 out of 12,186 institutions that participated in the publication of more than 25 articles from 2017 to 2021. The top 10 institutions in terms of publications and centrality are listed in Supplementary Table 6 . Harvard Medical School had the largest number of publications ( n  = 329) among institutions worldwide, followed by the Chinese Academy of Sciences ( n  = 305) and the University of California San Diego ( n  = 225). The institutions cooperation network is shown in Figure 5B . The Harvard Medical School and the University of California San Diego are active institutions in this research filed in both publications and cooperation. There an obvious inner-country cooperation trend in the institutions cooperation network, especially in United States and China due to their large number of publications. But institutions cooperation network in the United States is more intensive than in China.

Author cooperation

Up to 79,972 authors were involved in the publication of the 18,049 articles from2017 to 2021, and a total of 218 authors participated in the publication of at least 25 articles. Detailed information on the top 10 authors in terms of publications and centrality is provided in Supplementary Table 7 . Rob Knight is the most prolific author in the field of gut microbiome and disease, followed by Wei Chen and Hao Zhang. The author cooperation network is shown in Figure 5C . Similar to the institutions cooperation network, the inner-country cooperation pattern is also observed in the author cooperation network.

Journal analysis

114 out of 2,720 journals published more than 25 articles on the gut microbiome and disease over the 5 years. As shown in Supplementary Table 8 , the top 20 journals with the highest number of articles included 4,356 records, which accounts for 24.13% of the total. Scientific reports are the most productive journal, with 605 articles in this field, followed by Frontiers in microbiology (510) and Plos one (409). Although Gut ranks 19th in terms of the number of articles published, it has the highest IF (23.059) among the 20 journals, followed by Nature communications (22.059) and Microbiome (14.650), and Gut is the most-cited journal with 92.879 citations per article. There was a significant positive correlation between impact factor values and the citations per article (R 2  = 0.869, p  < 0.001) for the top 20 most productive journals ( Supplementary Figure 9 ).

Hot topics and emerging trend

By combining Figure 2 with Figure 3 , we can see that diseases that have attracted continuous attention are IBD, UC and CD. In contrast, other diseases have come into researchers’ notice in recent years, such as obesity, dysbiosis, diabetes, cardiovascular disease, Alzheimer’s disease, Parkinson’s disease, hypertension, depression and COVID-19. Compared to diet/nutrition and drugs, probiotics draw more attention, while FMT can be identified as a frontier of research.

The data of publications in the recent 5 years is used to assess the current research status of gut microbiome and disease. The timeline view of keywords co-occurrence network reveals the development of gut microbiome and disease ( Supplementary Figure 10 ). This network is divided into 21 clusters, which present the major subtopics in this field. Except “#0 growth performance” and “#14 oral microbiome” is irrelevant, other can be consider ongoing topics in recent. Campylobacter jejuni is commonly found in animal feces and causes human gastroenteritis, but the average year of “#16 campylobacter jejuni” is older than other clusters. In addition to utilizing keywords, co-cited references are also used to detect research hotspots and emerging trends. A total of 13 clusters are identified in the co-cited references network, and each cluster corresponds to a line of research ( Figure 6 ). Except “#7 Aquaculture”, other clusters closely related to this field. Among these clusters, “#0 Inflammatory bowel disease” contains most of the nodes, which means that it has been widely reported. “#1 Metatrascriptomics” has most of the citation burst articles, followed by “#5 Multiple sclerosis,” “#3 trimethylamine N-oxide,” “#2 Parkinson’s disease,” which indicate they are active research areas.

Co-cited references network from 2017 to 2021. Each node represents a cited article.

Diseases related to gut microbiome

A total of 541 diseases and conditions are retrieved from the Centers for Disease Control and Prevention (CDC, https://www.cdc.gov/DiseasesConditions/ ) and the Illinois Department of Public Health (IDPH, https://dph.illinois.gov/topics-services/diseases-and-conditions.html ), and they are used to search against WoSCC to depict research status of the gut microbiome with them. 73 diseases and conditions have more than 100 records in WoSCC from 1996 to 2021, and their publications trend are visualized in Figure 7 . “Overweight and Obesity” is an area of focus, possessing the largest number of articles. While, “Stress” ranked second, possibly because of its lexical ambiguity and irrelevant articles are hit. Gut-related diseases have been more reported than others, which are consistent with previous results. There are 5,984 records related to gut microbiome and cancers, and 19 types of cancers are involved. Colorectal (Colon) Cancer is in the first echelon with the largest amount of records ( n  = 2,489), and the second echelon includes Breast Cancer, Prostate Cancer, Lung Cancer, Pancreatic Cancer, Leukemia and Liver Cancer, and others belongs to the third echelon with records less than 50 ( Supplementary Figure 11 ).

Publication trend of diseases and conditions related to gut microbiome from 1998 to 2021.

Due to limitation of database, the earliest document is in 1996 in this study. But the first publication in this filed actually could trace back to 1958, when Eiseman et al. reported the successful treatment of pseudomembranous enterocolitis using a faecal enema ( Eiseman et al., 1958 ). Studies about the gut microbiome and disease have increased tremendously over the last decades and present exponential growth, which revealed the important role of the gut microbiome in human health and disease ( Gebrayel et al., 2022 ). Given that there are many unknowns about the gut microbiome and their potential applications in the prevention, diagnosis and therapy of diseases, this research scope will continue to attract keen interest among scientists, and further explorations will be conducted in the future.

To date, numerous studies have indicated that the intestinal microbiome is associated with various diseases, particularly digestive tract diseases ( Nouvenne et al., 2018 ). However, most of them were observational (i.e., different in diversity, taxa, OTU and functions among groups) and did not reveal cause and effect ( Koh and Bäckhed, 2020 ; Walter et al., 2020 ). It’s necessary to rethink whether there are causal relationships and whether the microbiota is a dominant or a crucial driving factor when surveying gut microbiome in diseases. Metabolites play an essential role in interactions between microbes and host cells, the altered composition of microbes could bring about a cascading impact on the immune system, and then effect the host health status ( Rooks and Garrett, 2016 ). Currently, the most extensively studied metabolites are SCFA, bile acids, TMAO, and amino acid-derived metabolites ( Liu et al., 2022 ), and other microbial metabolites such as lipids ( Schoeler and Caesar, 2019 ), carbohydrates ( Cheng et al., 2020 ) have also been proved to be essential for microbe-host interaction. However, comprehensive mechanisms that explain the link between the gut microbiome and most diseases remain poorly understood. Therefore, we encourage researchers to generate hypotheses based on observed differences in taxa and functions, and to independently validate it whenever possible.

The recent development of multi-omics approaches, such as metataxonomics [16S rRNA and ITS (Internal Transcribed Spacer) sequencing], shotgun metagenomics, metatranscriptomics, metaproteomics, and metabolomics, has enabled efficient characterization of microbial communities. These techniques not only provide the taxonomic profile of the microbial community but also assess their latent functions and metabolic activities ( Zhang et al., 2019 ). The biomarkers detected by these -omics technologies could help to elucidate potential mechanisms of these commensals in health and disease ( Lloyd-Price et al., 2019 ; Zhou et al., 2019 ; Mars et al., 2020 ). However, this also brings challenges to multi-omics data integration and mining ( Whon et al., 2021 ). Currently, methods of data integration include two categories, i.e., multi-staged analysis and meta-analysis. Multi-staged integration means using two or more categorical features of the data. For example, metagenomics is combined with metabolomics ( Oh et al., 2020 ). Meta-analysis attempts to systematically merge data across multiple studies and transform it into metadata that can be analyzed simultaneously ( Armour et al., 2019 ; Wang et al., 2021 ; Drewes et al., 2022 ), which reduce study bias, increase statistical power and improve overall biological understanding of a study effect. As for data mining, machine learning has been applied to find biomarkers and carry out classification or prediction tasks, such as diagnosis, disease course, and disease severity ( Marcos-Zambrano et al., 2021 ). But its limitation is requiring large amounts of data and lacking of interpretability. There are platforms and tools developed for multi-omics data integrating and mining, such as Qiita ( Gonzalez et al., 2018 ), MicrobiomeAnalyst ( Dhariwal et al., 2017 ), NetMoss ( Xiao et al., 2022 ), tmap ( Liao et al., 2019 ), which may aid in understanding the correlation between the gut microbiome and disease.

Besides investigating the relationship and mechanisms between the gut microbiome and diseases, it also is an interesting subject to modulate the gut microbiota to benefit health and reduce the risk of diseases. The main intervention strategies include diet/nutrition, dietary supplement, medicine and FMT. Diet is a feasible and easy measure to maintain homeostasis or increase the diversity of the gut microbiota. The question is, what type of diet can help to establish a good and stable intestinal microbiota ( Leeming et al., 2019 ). Previous studies have indicated that FMT could restore gut microbial diversity and eliminate Clostridioides difficile infection (CDI; Kelly et al., 2021 ), which has encouraged research into the use of FMT for other diseases, such as ulcerative colitis and Crohn’s disease. While, results of FMT are not always desirable and the effectiveness is highly variable ( Nie et al., 2019 ). It is assumed that the beneficial functions of therapeutic microbes are based on colonization and retention in sufficient quantity for enough time in recipients ( Lee et al., 2017 ; Chu et al., 2021 ). Therefore, the selection of appropriate donors or its microbes and efficient colonization plays an essential role in patient response ( Woodworth et al., 2017 ; Jouhten et al., 2020 ). It is also important to take into consideration how to appropriately evaluate the safety and efficacy for a given intervention ( Green et al., 2020 ; Haifer et al., 2021 ). It is possible and valuable to develop novel diagnostic, prognostic and therapeutic strategies based on microbiome manipulation. The management of common diseases could be transformed by translating microbiome research into treatments that regulate the microbiome. Although there are some microbiome interventions as effective treatment for improving health conditions, its detail mechanisms are not fully understood.

As one of the hot topics in gut microbiome and diseases, IBD is a chronic inflammatory gut pathological condition, and represented by CD and UC. Both diseases are characterized by diarrhea, rectal bleeding, abdominal pain, fatigue and weight loss, but differentiate in clinical manifestations of inflammation and intestinal localization ( Le Berre et al., 2020 ). Although a complete understanding of IBD pathogenesis is unclear, various risk factors associated with IBD have been identified, such as host genetic susceptibility, environmental variables, immune response and gut microbiome ( Chang, 2020 ). Indeed, studies in human subjects have shown that the gut microbiome is significant different in patients with IBD compared with that in healthy individuals ( Halfvarson et al., 2017 ; Lloyd-Price et al., 2019 ), such as reduced species richness and diversity, and lower temporal stability. Among them, the certain microbial taxa that are enriched or depleted in IBD, including bacteria, archaea, fungi, and viruses ( Iliev and Cadwell, 2021 ), is usually interpreted as the imbalance between beneficial and pathogenic microbe, however, the results differ between studies ( Schirmer et al., 2019 ). Alteration of gut microbial metabolites in IBD patients also detected, including fatty acids, amino acids and derivatives and bile acids, which may act as key regulators in the pathogenesis of IBD ( Li et al., 2022 ; Paik et al., 2022 ). Although UC and CD are similar in epidemiologic, immunologic, therapeutic and clinical features, they fell into two distinct groups at the gut microbiome pattern ( Pascal et al., 2017 ). The shifts in gut microbial community have been proven to be potential as diagnostic biomarkers of IBD ( Zhou et al., 2018 ; Guo et al., 2022 ), which could be used to develop non-invasive diagnostic or monitor methods, while independent external validation is necessary before it can be used in clinic. There are therapeutic advances in gut microbiome modulation in patients with IBD, and a variety of microbiome-modulating interventions are proposed for treatment, such as probiotics, prebiotics, antibiotics, FMT, and dietary supplements ( Eindor-Abarbanel et al., 2021 ). However, retrospective studies and meta-analyses on antibiotic use in UC and CD and long-term outcomes are controversial ( Ledder, 2019 ). Similarly, the use of probiotics for the effective treatment of IBD remains inconclusive ( Zhao et al., 2018 ). Due to the complexity and variety of IBD pathogenesis, personalized and multidimensional treatment will likely be required where microbiome-modulating therapy is coupled with other therapies. Changes in the gut microbiome seemed to play an important role in the onset of IBD, yet longitudinal studies of the gut microbiome are needed to move from association toward causation and modulation.

The research of the gut microbiome in human health and disease remains loaded with challenges. Gut microbiota is a complex and dynamic consortium influenced by multiple factors ( Spencer et al., 2019 ; Kurilshikov et al., 2021 ; Gacesa et al., 2022 ). Changes in hosts’ lifestyle, such as diet, medication use, age, and socioeconomic status can lead to data reproducibility problems and statistical underpower. Recruiting participants with well-defined disease or at-risk conditions and well data management is important to reduce background noise. In addition, relatively few controlled samples in the trial may cause inconsistent results in the same disease. Because of the need for long longitudinal study, the influence from sample collection and storage and batch effects need to be avoided ( Wang and LêCao, 2020 ; Poulsen Casper et al., 2021 ). Nowadays, gut microbiome research involves multi-disciplinary, not only microbiology and gastroenterology but also bioinformatics, mathematics, biochemistry, immunology and ecology, which pose challenges for single researcher ( Mirzayi et al., 2021 ). There are gaps in scientific and technological power among countries, United States has established its leadership in this field. Therefore, we propose to enhance coordination and collaboration across the field among scientific communities to tackle shared challenges and explore new frontiers jointly. At present, inner-country cooperation pattern was observed at the institution and author levels, while a dynamic analysis of the collaboration networks based on different periods can show the evolution of collaborated patterns ( Yu et al., 2020a ). Effective international cooperation could promote academic exchanges. It may be a solution to the research of gut microbiome in disease by conducting well-designed large-scale cohort studies and randomized clinical trials, meanwhile combining multi-omics techniques and integrating microbiome data ( Heintz-Buschart et al., 2016 ; Park et al., 2022 ). Due to confounding factors, it is necessary to establish standardized experimental procedures and subsequent data analysis pipelines ( Szóstak et al., 2022 ). While experimental animal models can provide fascinating insights into the role of the microbiome in disease states, they rarely recapitulate the complete human phenotype ( Hugenholtz and de Vos, 2018 ; Kieser et al., 2022 ). Therefore, extrapolations to human diseases have to be viewed with caution, and more rigorous experiments are required. The current focus concerning gut microbiota is mainly on bacteria, which neglects the significance of microbial intra- and inter-kingdom interaction. Fungi and viruses also impact the gut microbiota and host ( van Tilburg Bernardes et al., 2020 ), although knowledge about their relationship with dysbiosis is limited ( Carding et al., 2017 ; Beller and Matthijnssens, 2019 ). A recent study identified signature fungi in colorectal cancer and adenoma patients from multiple cohorts, and observed trans-kingdom interactions between enteric fungi and bacteria in colorectal cancer progression ( Lin et al., 2022 ).

Bibliometric analysis is increasingly being used to assess hot topics and emerging areas of a specific field. Compared to narrative reviews that provide qualitative summary and commentary of published literature in a field, it quantitatively investigates the status of interdisciplinary fields based on citations and other statistical information regarding publications. In the future, the combination of the two will present a more precise historical context and future trajectory for a field. There are situations that need to be balanced in bibliometric analysis. The first situation is choosing databases. Other databases such as PubMed and Scopus also can be set as the data source, Scopus covers even more journals and also contains citation records. However, Web of Science (WoS) assigns document type labels more accurately than Scopus ( Yeung, 2019 ), and we only filtered for original articles for the downstream analysis. The second situation is setting a search strategy. Well-defined search terms should include publications related to the field and exclude irrelevant ones as far as possible. It seems to be inevitable to contain irrelevant publications except for manual verification, but we believe that it is reliable to reflect the global trend and hot topics by these multi-aspect analysis. Artificial intelligence technology has the potential to realize semantic detection of publications and determine whether they belong to a specific theme. This would be especially useful for bibliometric analysis with massive volume of data and improve the accuracy of results.

Bibliometric methods are quantitative by nature to examine unlimited quantities of publications. But our study also comes with certain limitations. Firstly, due to the nature of the bibliometric methodology, the relationship between some bibliometric metrics and their assertions about research quality is often unclear ( Wallin, 2005 ). Secondly, our study only retrieved data from WoS, yet a combination with other databases can be performed in similar type of research. Thirdly, synonymous words need be merged together during the analysis.

In conclusion, based on the detailed bibliometrics analysis of gut microbiome and disease, we present a comprehensive overview of this evolving subject over the past 26 years. These results indicate that gut microbiome and disease is an active research field, and publications on this subject have proliferated over the past decades. The current research mainly focuses on gastrointestinal diseases, while extra-intestinal diseases are also rising, such as nerve-related diseases. Although extensive correlative studies have been performed, the molecular mechanisms still need to be explored. Overall, gut microbiome research shows a multitude of challenges and great opportunities.

Data availability statement

Author contributions.

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by ZH, KL, and WM. The first draft of the manuscript was written by ZH and all authors commented on previous versions of the manuscript. All authors contributed to the article and approved the submitted version.

This project was supported by Science and Technology innovation Plan of Shanghai (19391902000).

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Acknowledgments

We would like to acknowledge the tremendous work and effort of our research team and we are deeply grateful for their constant support.

1 https://clarivate.com/

Supplementary material

The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmicb.2022.1018594/full#supplementary-material

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New class of antimicrobials discovered in soil bacteria

Scientists have mined streptomyces for antibiotics for nearly a century, but the newly identified umbrella toxin escaped notice.

Researchers have discovered toxic protein particles, shaped like umbrellas, that soil bacteria known as Streptomyces secrete to squelch competitors, especially others of their own species.

The discovery of the umbrella toxin particles and related information about their structures, composition and mode of action were published April 17 in Nature .

The umbrella toxin proteins are the latest example of these bacteria's varied, combative strikes on their microscopic rivals. The crowded, diverse bacteria communities in which they live are a melee of antimicrobial attacks, counterattacks and defenses.

Ironically, many clinically used antibiotics are derived directly from, or are inspired by, molecules that bacteria use against each other in their natural habitat . Streptomyces' chemical weaponry against their competitors is one of the richest sources of such molecules. Among them is the common, broad-spectrum drug streptomycin.

What makes these newly detected antibacterial toxins different is that, unlike the Streptomyces' small-molecule antibiotics, umbrella toxins are large complexes composed of multiple proteins. They are also far more specific in the bacteria they target.

The authors of the Nature paper speculate that these properties of umbrella toxins explain why they escaped discovery for more than 100 years of research on toxins produced by Streptomyces.

Genes encoding umbrella toxins were originally uncovered through a bioinformatics search for new bacterial toxins. In biochemical and genetic experiments led by Qinqin Zhao in Joseph Mougous' microbiology lab at the University of Washington School of Medicine, the scientists learned that these toxins associate with other proteins in a large complex.

Cryo-electron microscopy of these protein complexes was performed by Young Park in the laboratory of David Veesler, professor of biochemistry at the UW School of Medicine and an investigator of the Howard Hughes Medical Institute.

These studies revealed that the toxin complexes Qinqin isolated adopt a striking appearance befitting their discovery in Seattle. They look like umbrellas.

"The shape of these particles is quite peculiar, and it will be interesting in future work to learn how their unusual morphology helps them eliminate target bacteria," noted Mougous, a professor of microbiology at the UW School of Medicine and a Howard Hughes Medical Institute investigator.

The scientists then sought to determine the targets of these toxins by screening their effects on every organism they could conceivably target, from fungi to 140 different bacteria, including some taken from sorghum plants in the lab of study author Devin Coleman at the University of California-Berkeley and the U.S. Department of Agriculture Agricultural Research Service. .

Among these potential adversaries, the toxins specifically targeted their own brethren: other Streptomyces species.

"We think this exquisite specificity may be due to the proteins that make up the spokes of the umbrella, which vary across the particles. These include proteins that might latch onto specific sugars found on the surface of competitor bacteria," commented study author S. Brook Peterson, a senior scientist in the Mougous lab.

By analyzing the thousands of publicly available bacterial genomes, study authors Dapeng Zhang of St. Louis University and his graduate student Youngjun Tan found that many other species of bacteria also have the genes to manufacture umbrella particle toxins. Interestingly, these species all form branching filaments, an unusual mode of growth among bacteria.

In addition to the many questions remaining to be answered about the basic biology of umbrella toxin particles, Mougous and his colleagues are intrigued by their potential clinical applications.

They suspect that the bacteria that cause tuberculosis and diphtheria may be sensitive to umbrella toxins. They note these same bacteria have become resistant to traditional antibiotics. Umbrella toxin particles might be worth exploring, the scientists suggested, for their potential to subdue these serious disease-causing bacteria.

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Materials provided by University of Washington School of Medicine/UW Medicine . Note: Content may be edited for style and length.

Journal Reference :

• Qinqin Zhao, Savannah Bertolli, Young-Jun Park, Yongjun Tan, Kevin J. Cutler, Pooja Srinivas, Kyle L. Asfahl, Citlali Fonesca-García, Larry A. Gallagher, Yaqiao Li, Yaxi Wang, Devin Coleman-Derr, Frank DiMaio, Dapeng Zhang, S. Brook Peterson, David Veesler, Joseph D. Mougous. Streptomyces umbrella toxin particles block hyphal growth of competing species . Nature , 2024; DOI: 10.1038/s41586-024-07298-z

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100+ microbiology research topics to succeed.

Microbiology topics are some of the most researched ideas. This field entails the study of different microorganisms, ranging from eukaryotic fungi and single-celled organisms to cell-cluster organisms. When pursuing a microbiology course in a university or college, your educators will ask you to write academic papers on microbiology research topics.

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Suggestions or feedback?

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Advancing technology for aquaculture

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According to the National Oceanic and Atmospheric Administration, aquaculture in the United States represents a $1.5 billion industry annually. Like land-based farming, shellfish aquaculture requires healthy seed production in order to maintain a sustainable industry. Aquaculture hatchery production of shellfish larvae — seeds — requires close monitoring to track mortality rates and assess health from the earliest stages of life. 

Careful observation is necessary to inform production scheduling, determine effects of naturally occurring harmful bacteria, and ensure sustainable seed production. This is an essential step for shellfish hatcheries but is currently a time-consuming manual process prone to human error. 

With funding from MIT’s Abdul Latif Jameel Water and Food Systems Lab (J-WAFS), MIT Sea Grant is working with Associate Professor Otto Cordero of the MIT Department of Civil and Environmental Engineering, Professor Taskin Padir and Research Scientist Mark Zolotas at the Northeastern University Institute for Experiential Robotics, and others at the Aquaculture Research Corporation (A.R.C.), and the Cape Cod Commercial Fishermen’s Alliance, to advance technology for the aquaculture industry. Located on Cape Cod, A.R.C. is a leading shellfish hatchery, farm, and wholesaler that plays a vital role in providing high-quality shellfish seed to local and regional growers.

Two MIT students have joined the effort this semester, working with Robert Vincent, MIT Sea Grant’s assistant director of advisory services, through the Undergraduate Research Opportunities Program (UROP). 

First-year student Unyime Usua and sophomore Santiago Borrego are using microscopy images of shellfish seed from A.R.C. to train machine learning algorithms that will help automate the identification and counting process. The resulting user-friendly image recognition tool aims to aid aquaculturists in differentiating and counting healthy, unhealthy, and dead shellfish larvae, improving accuracy and reducing time and effort.

Vincent explains that AI is a powerful tool for environmental science that enables researchers, industry, and resource managers to address challenges that have long been pinch points for accurate data collection, analysis, predictions, and streamlining processes. “Funding support from programs like J-WAFS enable us to tackle these problems head-on,” he says. 

ARC faces challenges with manually quantifying larvae classes, an important step in their seed production process. "When larvae are in their growing stages they are constantly being sized and counted,” explains Cheryl James, A.R.C. larval/juvenile production manager. “This process is critical to encourage optimal growth and strengthen the population." 

Developing an automated identification and counting system will help to improve this step in the production process with time and cost benefits. “This is not an easy task,” says Vincent, “but with the guidance of Dr. Zolotas at the Northeastern University Institute for Experiential Robotics and the work of the UROP students, we have made solid progress.” 

The UROP program benefits both researchers and students. Involving MIT UROP students in developing these types of systems provides insights into AI applications that they might not have considered, providing opportunities to explore, learn, and apply themselves while contributing to solving real challenges.

Borrego saw this project as an opportunity to apply what he’d learned in class 6.390 (Introduction to Machine Learning) to a real-world issue. “I was starting to form an idea of how computers can see images and extract information from them,” he says. “I wanted to keep exploring that.”

Usua decided to pursue the project because of the direct industry impacts it could have. “I’m pretty interested in seeing how we can utilize machine learning to make people’s lives easier. We are using AI to help biologists make this counting and identification process easier.” While Usua wasn’t familiar with aquaculture before starting this project, she explains, “Just hearing about the hatcheries that Dr. Vincent was telling us about, it was unfortunate that not a lot of people know what’s going on and the problems that they’re facing.”

On Cape Cod alone, aquaculture is an $18 million per year industry. But the Massachusetts Division of Marine Fisheries estimates that hatcheries are only able to meet 70–80 percent of seed demand annually, which impacts local growers and economies. Through this project, the partners aim to develop technology that will increase seed production, advance industry capabilities, and help understand and improve the hatchery microbiome.

Borrego explains the initial challenge of having limited data to work with. “Starting out, we had to go through and label all of the data, but going through that process helped me learn a lot.” In true MIT fashion, he shares his takeaway from the project: “Try to get the best out of what you’re given with the data you have to work with. You’re going to have to adapt and change your strategies depending on what you have.”

Usua describes her experience going through the research process, communicating in a team, and deciding what approaches to take. “Research is a difficult and long process, but there is a lot to gain from it because it teaches you to look for things on your own and find your own solutions to problems.”

In addition to increasing seed production and reducing the human labor required in the hatchery process, the collaborators expect this project to contribute to cost savings and technology integration to support one of the most underserved industries in the United States. 

Borrego and Usua both plan to continue their work for a second semester with MIT Sea Grant. Borrego is interested in learning more about how technology can be used to protect the environment and wildlife. Usua says she hopes to explore more projects related to aquaculture. “It seems like there’s an infinite amount of ways to tackle these issues.”

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• Department of Civil and Environmental Engineering
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• Cape Cod Commercial Fishermen's Alliance
• Northeastern University Institute for Experiential Robotics

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Microbial adaptability in changing environments

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Abs, E., Chase, A. B. & Allison, S. D. How do soil microbes shape ecosystem biogeochemistry in the context of global change? Environ. Microbiol. 25 , 780–785 (2023).

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Cruz-Paredes, C., Tájmel, D. & Rousk, J. Variation in temperature dependences across Europe reveals the climate sensitivity of soil microbial decomposers. Appl. Environ. Microbiol. 89 , e02090-22 (2023).

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Two key brain systems are central to psychosis, Stanford Medicine-led study finds

When the brain has trouble filtering incoming information and predicting what’s likely to happen, psychosis can result, Stanford Medicine-led research shows.

April 11, 2024 - By Erin Digitale

People with psychosis have trouble filtering relevant information (mesh funnel) and predicting rewarding events (broken crystal ball), creating a complex inner world. Emily Moskal

Inside the brains of people with psychosis, two key systems are malfunctioning: a “filter” that directs attention toward important external events and internal thoughts, and a “predictor” composed of pathways that anticipate rewards.

Dysfunction of these systems makes it difficult to know what’s real, manifesting as hallucinations and delusions. 

The findings come from a Stanford Medicine-led study , published April 11 in  Molecular Psychiatry , that used brain scan data from children, teens and young adults with psychosis. The results confirm an existing theory of how breaks with reality occur.

“This work provides a good model for understanding the development and progression of schizophrenia, which is a challenging problem,” said lead author  Kaustubh Supekar , PhD, clinical associate professor of psychiatry and behavioral sciences.

The findings, observed in individuals with a rare genetic disease called 22q11.2 deletion syndrome who experience psychosis as well as in those with psychosis of unknown origin, advance scientists’ understanding of the underlying brain mechanisms and theoretical frameworks related to psychosis.

During psychosis, patients experience hallucinations, such as hearing voices, and hold delusional beliefs, such as thinking that people who are not real exist. Psychosis can occur on its own and isa hallmark of certain serious mental illnesses, including bipolar disorder and schizophrenia. Schizophrenia is also characterized by social withdrawal, disorganized thinking and speech, and a reduction in energy and motivation.

It is challenging to study how schizophrenia begins in the brain. The condition usually emerges in teens or young adults, most of whom soon begin taking antipsychotic medications to ease their symptoms. When researchers analyze brain scans from people with established schizophrenia, they cannot distinguish the effects of the disease from the effects of the medications. They also do not know how schizophrenia changes the brain as the disease progresses. 

To get an early view of the disease process, the Stanford Medicine team studied young people aged 6 to 39 with 22q11.2 deletion syndrome, a genetic condition with a 30% risk for psychosis, schizophrenia or both. 

Kaustubh Supekar

Brain function in 22q11.2 patients who have psychosis is similar to that in people with psychosis of unknown origin, they found. And these brain patterns matched what the researchers had previously theorized was generating psychosis symptoms.

“The brain patterns we identified support our theoretical models of how cognitive control systems malfunction in psychosis,” said senior study author  Vinod Menon , PhD, the Rachael L. and Walter F. Nichols, MD, Professor; a professor of psychiatry and behavioral sciences; and director of the  Stanford Cognitive and Systems Neuroscience Laboratory .

Thoughts that are not linked to reality can capture the brain’s cognitive control networks, he said. “This process derails the normal functioning of cognitive control, allowing intrusive thoughts to dominate, culminating in symptoms we recognize as psychosis.”

Cerebral sorting  

Normally, the brain’s cognitive filtering system — aka the salience network — works behind the scenes to selectively direct our attention to important internal thoughts and external events. With its help, we can dismiss irrational thoughts and unimportant events and focus on what’s real and meaningful to us, such as paying attention to traffic so we avoid a collision.

The ventral striatum, a small brain region, and associated brain pathways driven by dopamine, play an important role in predicting what will be rewarding or important. 

For the study, the researchers assembled as much functional MRI brain-scan data as possible from young people with 22q11.2 deletion syndrome, totaling 101 individuals scanned at three different universities. (The study also included brain scans from several comparison groups without 22q11.2 deletion syndrome: 120 people with early idiopathic psychosis, 101 people with autism, 123 with attention deficit/hyperactivity disorder and 411 healthy controls.) 

The genetic condition, characterized by deletion of part of the 22nd chromosome, affects 1 in every 2,000 to 4,000 people. In addition to the 30% risk of schizophrenia or psychosis, people with the syndrome can also have autism or attention deficit hyperactivity disorder, which is why these conditions were included in the comparison groups.

The researchers used a type of machine learning algorithm called a spatiotemporal deep neural network to characterize patterns of brain function in all patients with 22q11.2 deletion syndrome compared with healthy subjects. With a cohort of patients whose brains were scanned at the University of California, Los Angeles, they developed an algorithmic model that distinguished brain scans from people with 22q11.2 deletion syndrome versus those without it. The model predicted the syndrome with greater than 94% accuracy. They validated the model in additional groups of people with or without the genetic syndrome who had received brain scans at UC Davis and Pontificia Universidad Católica de Chile, showing that in these independent groups, the model sorted brain scans with 84% to 90% accuracy.

The researchers then used the model to investigate which brain features play the biggest role in psychosis. Prior studies of psychosis had not given consistent results, likely because their sample sizes were too small. 

Vinod Menon

Comparing brain scans from 22q11.2 deletion syndrome patients who had and did not have psychosis, the researchers showed that the brain areas contributing most to psychosis are the anterior insula (a key part of the salience network or “filter”) and the ventral striatum (the “reward predictor”); this was true for different cohorts of patients.

In comparing the brain features of people with 22q11.2 deletion syndrome and psychosis against people with psychosis of unknown origin, the model found significant overlap, indicating that these brain features are characteristic of psychosis in general.

A second mathematical model, trained to distinguish all subjects with 22q11.2 deletion syndrome and psychosis from those who have the genetic syndrome but without psychosis, selected brain scans from people with idiopathic psychosis with 77.5% accuracy, again supporting the idea that the brain’s filtering and predicting centers are key to psychosis.

Furthermore, this model was specific to psychosis: It could not classify people with idiopathic autism or ADHD.

“It was quite exciting to trace our steps back to our initial question — ‘What are the dysfunctional brain systems in schizophrenia?’ — and to discover similar patterns in this context,” Menon said. “At the neural level, the characteristics differentiating individuals with psychosis in 22q11.2 deletion syndrome are mirroring the pathways we’ve pinpointed in schizophrenia. This parallel reinforces our understanding of psychosis as a condition with identifiable and consistent brain signatures.” However, these brain signatures were not seen in people with the genetic syndrome but no psychosis, holding clues to future directions for research, he added.

Applications for treatment or prevention

In addition to supporting the scientists’ theory about how psychosis occurs, the findings have implications for understanding the condition — and possibly preventing it.

“One of my goals is to prevent or delay development of schizophrenia,” Supekar said. The fact that the new findings are consistent with the team’s prior research on which brain centers contribute most to schizophrenia in adults suggests there may be a way to prevent it, he said. “In schizophrenia, by the time of diagnosis, a lot of damage has already occurred in the brain, and it can be very difficult to change the course of the disease.”

“What we saw is that, early on, functional interactions among brain regions within the same brain systems are abnormal,” he added. “The abnormalities do not start when you are in your 20s; they are evident even when you are 7 or 8.”

Our discoveries underscore the importance of approaching people with psychosis with compassion.

The researchers plan to use existing treatments, such as transcranial magnetic stimulation or focused ultrasound, targeted at these brain centers in young people at risk of psychosis, such as those with 22q11.2 deletion syndrome or with two parents who have schizophrenia, to see if they prevent or delay the onset of the condition or lessen symptoms once they appear. 

The results also suggest that using functional MRI to monitor brain activity at the key centers could help scientists investigate how existing antipsychotic medications are working. 

Although it’s still puzzling why someone becomes untethered from reality — given how risky it seems for one’s well-being — the “how” is now understandable, Supekar said. “From a mechanistic point of view, it makes sense,” he said.

“Our discoveries underscore the importance of approaching people with psychosis with compassion,” Menon said, adding that his team hopes their work not only advances scientific understanding but also inspires a cultural shift toward empathy and support for those experiencing psychosis. 

“I recently had the privilege of engaging with individuals from our department’s early psychosis treatment group,” he said. “Their message was a clear and powerful: ‘We share more similarities than differences. Like anyone, we experience our own highs and lows.’ Their words were a heartfelt appeal for greater empathy and understanding toward those living with this condition. It was a call to view psychosis through a lens of empathy and solidarity.”

Researchers contributed to the study from UCLA, Clinica Alemana Universidad del Desarrollo, Pontificia Universidad Católica de Chile, the University of Oxford and UC Davis.

The study was funded by the Stanford Maternal and Child Health Research Institute’s Uytengsu-Hamilton 22q11 Neuropsychiatry Research Program, FONDEYCT (the National Fund for Scientific and Technological Development of the government of Chile), ANID-Chile (the Chilean National Agency for Research and Development) and the U.S. National Institutes of Health (grants AG072114, MH121069, MH085953 and MH101779).

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu .

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Understanding the Female Reproductive Microbiome in Livestock

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For decades, techniques in Microbiology allowed researchers to study only a small proportion of microorganisms inhabiting a body site, due to techniques relying on culture of bacteria in selective media, thus neglecting species of bacteria that fail to grow under these conditions. Recent advances in genome ...

Keywords : bovine microbiome, reproductive microbiome, commensal microbes, fertility, livestock

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Research: How to Close the Gender Gap in Startup Financing

• Malin Malmström,
• Barbara Burkhard,
• Charlotta Sirén,
• Dean Shepherd,
• Joakim Wincent

Three ways policymakers, financiers, and other stakeholders can mitigate gender bias in entrepreneurial funding.

A global analysis of previous research over the last three decades shows that women entrepreneurs face a higher rate of business loan denials and increased interest rates in loan decisions made by commercial bankers. Interestingly, the data also reveals that the formal and informal standing of women in a particular society can provide clues to some of the true hurdles to positive change. This article reviews these hurdles, and offers three recommendations for change.

Gender disparities persist in entrepreneurship and statistics reveal the severity of the issue. Globally, only one in three businesses is owned by women . In 2019, the share of startups with at least one female founding member was a mere 20% .

• MM Malin Malmström is a professor of entrepreneurship and innovation at Luleå University of Technology, and a director of the research center Sustainable Finance Lab in Sweden.
• BB Barbara Burkhard is a postdoctoral researcher of entrepreneurship at the Institute of Responsible Innovation at the University of St.Gallen.
• CS Charlotta Sirén is an associate professor of management at the Institute of Responsible Innovation at the University of St.Gallen.
• DS Dean Shepherd is a professor of entrepreneurship, management, and organization at The Mendoza College of Business, University of Notre Dame.
• JW Joakim Wincent is a professor of entrepreneurship and management at the Hanken School of Economics and the Global Center for Entrepreneurship and Innovation at the University of St.Gallen.

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