recent research topics in microbiology 2021

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Role of tenofovir dipivoxil in gut microbiota recovery from HBV-infection induced dysbiosis

Studies have found dysbiosis of the gut microbiota in individuals infected with the hepatitis B virus (HBV). Tenofovir dipivoxil (TDF) is one of the preferred oral antiviral drugs used for the treatment of chr...

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Application of MALDI-TOF mass spectrometry for identification of Nocardia species

Nocardiosis, despite its rarity and underreporting, is significant due to its severe impact, characterized by high morbidity and mortality rates. The development of a precise, reliable, rapid, and straightforw...

Isolation and antimicrobial susceptibility profile of Salmonella species from slaughtered cattle carcasses and abattoir personnel at Dessie, municipality Abattoir, Northeast Ethiopia

Antibiotic-resistant Salmonella is one of the main public health concerns in the world. Isolation of Salmonella in abattoirs has been considered the core source of infection in the community from meat. Still, the...

Diaporthe species causing shoot dieback of Acer (maple) in Henan Province, China

Maple is an important ornamental plant in China. With the increasing use of maple trees in landscaping, a symptom of shoot dieback has been observed in Henan province, China.

Potential of ZnO nanoparticles for multi-drug resistant Escherichia coli having CRISPR-Cas from poultry market in Lahore

Apart from known factors such as irrational use of antibiotics and horizontal gene transfer, it is now reported that clustered regularly interspaced short palindromic repeats (CRISPR) are also associated with ...

Occurrence rate and species and subtypes of Cryptosporidium spp. in pet dogs in Yunnan Province, China

Cryptosporidium spp. is a ubiquitous, globally distributed intestinal protozoan infecting humans and at least 260 animal hosts. Due to close human contact with pet dogs and identification of zoonotic Cryptosporid...

Genetic diversity, biofilm formation, and Vancomycin resistance of clinical Clostridium innocuum isolates

Clostridium innocuum , previously considered a commensal microbe, is a spore-forming anaerobic bacterium. C . innocuum displays inherent resistance to vancomycin and is associated with extra-intestinal infections, ...

Genetic and phenotypic diversity of Flavobacterium psychrophilum isolates from Czech salmonid fish farms

The salmonid pathogen Flavobacterium psychrophilum poses a significant economic threat to global aquaculture, yet our understanding of its genetic and phenotypic diversity remains incomplete across much of its ge...

EsxA, a type VII secretion system-dependent effector, reveals a novel function in the sporulation of Bacillus cereus ATCC14579

Bacillus cereus is a Gram-positive, spore-forming bacterium that produces a spectrum of effectors integral to bacterial niche adaptation and the development of various infections. Among those is EsxA, whose secre...

Lactic acid bacteria isolated from women’ breast milk and infants’ faeces have appreciable immunogenic and probiotic potentials against diarrheagenic E. coli strains

Diarrheal diseases remain the leading cause of high mortality among the infants, particularly in the developing countries; Probiotic intervention for diarrhea has been an ongoing novel approach to diarrheal pr...

Biological and genomic characterization of a polyvalent phage PSH-1 against multidrug-resistant Salmonella Enteritidis

Bacteriophage has been renewed attention as a new antibacterial agent due to the limitations of antibiotic treatment. Bacteriophages are generally thought to be highly host specific and even strain specific, b...

Extreme trophic tales: deciphering bacterial diversity and potential functions in oligotrophic and hypereutrophic lakes

Oligotrophy and hypereutrophy represent the two extremes of lake trophic states, and understanding the distribution of bacterial communities across these contrasting conditions is crucial for advancing aquatic...

Linezolid-resistant Enterococcus faecium clinical isolates from Pakistan: a genomic analysis

Linezolid-resistant Enterococcus faecium (LRE) is a global priority pathogen. Thirteen LRE were reported from clinical specimens between November 2021 and April 2023 at two laboratories in Karachi, Pakistan. We a...

Evaluation of 1021Bp, a close relative of Pseudomonas eucalypticola , for potential of plant growth promotion, fungal pathogen suppression and boxwood blight control

Pseudomonas eucalypticola , a new species of the P. fluorescens group that generates most Pseudomonas -based biocontrol agents, has not been found in any plants other than Eucalyptus dunnii leaves. Except for antag...

Isolate distribution and antifungal susceptibility of Saccharomyces cerevisiae in the national regional medical center of Southwest China for women and children during 2018–2023

Saccharomyces cerevisiae has been considered a harmless yeast, but in recent years, increasing evidence has shown that it can cause disease in humans, especially invasive infections in infants/children and vulvov...

Distribution of chaperone-usher fimbriae and curli fimbriae among uropathogenic Escherichia coli

In the present study, we aimed to determine the frequency of the csgA, fimH, mrkD, foc, papaGI, papGII and papGIII genes, to provide and to design fimbrial adhesin gene (FAG) patterns and profiles for the isolate...

The antagonistic activity of Streptomyces spiroverticillatus (No. HS1) against of poplar canker pathogen Botryosphaeria dothidea

Poplar canker caused by Botryosphaeria dothidea is one of the most severe plant disease of poplars worldwide. In our study, we aimed to investigate the modes of antagonism by fermentation broth supernatant (FBS) ...

Correlation of gut microbial diversity to sight-threatening diabetic retinopathy

To determine the association of gut microbiome diversity and sight-threatening diabetic retinopathy (STDR) amongst patients with pre-existing diabetes.

Acceleration of epithelial cell syndecan-1 shedding by anthrax hemolytic virulence factors

The bacterial and yeast microbiota in livestock forages in hungary.

Along bacteria, yeasts are common in forages and forage fermentations as spoilage microbes or as additives, yet few studies exist with species-level data on these fungi’s occurrence in feedstuff. Active dry ye...

Antimicrobial resistance profile and associated factors of hospital-acquired gram-negative bacterial pathogens among hospitalized patients in northeast Ethiopia

Antimicrobial resistance is a major global public health issue. Infections caused by resistant species are associated with higher mortality rates, longer hospital stays, medication failure, and rising medical ...

Evaluation of lyophilized bacteriophage cocktail efficiency against multidrug-resistant Salmonella in broiler chickens

Currently, phage biocontrol is increasingly used as a green and natural technology for treating Salmonella and other infections, but phages exhibit instability and activity loss during storage. Therefore, in this...

Metagenomic profiling of gut microbiota in Fall Armyworm ( Spodoptera frugiperda ) larvae fed on different host plants

The fall armyworm (FAW, Spodoptera frugiperda ) is a polyphagous pest known for causing significant crop damage. The gut microbiota plays a pivotal role in influencing the biology, physiology and adaptation of the...

Identification of hub genes and potential networks by centrality network analysis of PCR amplified Fusarium oxysporum f. sp. lycopersici EF1α gene

Fusarium wilt is a devastating soil-borne fungal disease of tomato across the world. Conventional method of disease prevention including usage of common pesticides and methods like soil solarisation are usuall...

Can pre-analytical procedures improve microbiological culture yield in patients with periprosthetic infections?

The detection of causative pathogens plays a crucial role in the diagnosis and targeted treatment of periprosthetic joint infections (PJI). While there have been improvements in analytic methods in the past, p...

Genomic portraits of methicillin-resistant staphylococci (MRS) from food fish unveiled the genes associated with staphylococcal food poisoning (SFP), virulence and antimicrobial resistance

Characteristics of non-clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) especially from fishery environment are poorly understood. This research, in addition to comprehensive characterisatio...

Evaluation of antifungal and apoptotic effects of linalool, citral, and carvacrol separately and in combination with nystatin against clinical isolates of Pichia kudriavzevii

Pichia kudriavzevii (formerly Candida krusei ) poses a significant threat to immunocompromised patients due to its inherent resistance to various antifungal drugs. This study explored the anticandidal potential of...

Correction: Enrichment of human nasopharyngeal bacteriome with bacteria from dust after short‑term exposure to indoor environment: a pilot study

The original article was published in BMC Microbiology 2023 23 :202

Evaluation of the synbiotic effects of Saccharomyces cerevisiae and mushroom extract on the growth performance, digestive enzyme activity, and immune status of zebrafish danio rerio

The quest for candidate probiotics and prebiotics to develop novel synbiotics for sustainable and profitable fish farming remains a major focus for various stakeholders. In this study, we examined the effects ...

DUF1127-containing protein and ProQ had opposite effects on biofilm formation in Vibrio alginolyticus

The RNA binding protein is crucial for gene regulation at the post transcription level. In this study, functions of the DUF1127-containing protein and ProQ, which are RNA-binding proteins, were revealed in Vibrio...

Streptomyces avermitilis MICNEMA2022: a new biorational strain for producing abamectin as an integrated nematode management agent

Abamectin (ABA) is considered a powerful insecticidal and anthelmintic agent. It is an intracellular product of Streptomyces avermitilis ; is synthesized through complicated pathways and can then be extracted from...

Antivirulence activities of Rutin-loaded chitosan nanoparticles against pathogenic Staphylococcus aureus

Staphylococcus aureus is an infectious bacterium that is frequently found in healthcare settings and the community. This study aimed to prepare rutin-loaded chitosan nanoparticles (Rut-CS NPs) and assess their an...

Mechanisms of ROS-mediated interactions between Bacillus aryabhattai LAD and maize roots to promote plant growth

Plant growth-promoting rhizobacteria (PGPR), as a group of environmentally friendly bacteria growing in the rhizosphere of plants, play an important role in plant growth and development and resistance to envir...

​Fusarium Protein Toolkit: a web-based resource for structural and variant analysis of Fusarium species

​​The genus Fusarium poses significant threats to food security and safety worldwide because numerous species of the fungus cause destructive diseases and/or mycotoxin contamination in crops. The adverse effects ...

Clinical and microbiological characteristics and follow-up of invasive Listeria monocytogenes infection among hospitalized patients: real-world experience of 16 years from Hungary

Invasive Listeria monocytogenes infection is rare, but can lead to life-threatening complications among high-risk patients. Our aim was to assess characteristics and follow-up of adults hospitalized with invasive...

Survival and virulence of Acinetobacter baumannii in microbial mixtures

Acinetobacter species such as A. venetianus and A. guillouiae have been studied for various biotechnology applications, including bioremediation of recalcitrant and harmful environmental contaminants, as well as ...

Phenotypic and genotypic determination of resistance to common disinfectants among strains of Acinetobacter baumannii producing and non-producing biofilm isolated from Iran

Nosocomial infections are a global problem in hospitals all around the world. It is considered a major health problem, especially in developing countries. The increase in the patient’s stay in hospitals has in...

Disruption of bacterial interactions and community assembly in Babesia -infected Haemaphysalis longicornis following antibiotic treatment

A previous study highlighted the role of antibiotic-induced dysbiosis in the tick microbiota, facilitating the transstadial transmission of Babesia microti from nymph to adult in Haemaphysalis longicornis . This s...

Biodegradation of low-density polyethylene by mixed fungi composed of Alternaria sp. and Trametes sp. isolated from landfill sites

With the development of industry and modern manufacturing, nondegradable low-density polyethylene (LDPE) has been widely used, posing a rising environmental hazard to natural ecosystems and public health. In t...

Antibacterial efficacy of mycobacteriophages against virulent Mycobacterium tuberculosis

Tuberculosis (TB) remains a major global health concern, with drug-resistant strains posing a significant challenge to effective treatment. Bacteriophage (phage) therapy has emerged as a potential alternative ...

Wolbachia strain diversity in a complex group of sympatric cryptic parasitoid wasp species

Maternally-inherited symbionts can induce pre-mating and/or post-mating reproductive isolation between sympatric host lineages, and speciation, by modifying host reproductive phenotypes. The large parasitoid w...

Differences in the landscape of colonized microorganisms in different oral potentially malignant disorders and squamous cell carcinoma: a multi-group comparative study

The role of microbes in diseases, especially cancer, has garnered significant attention. However, research on the oral microbiota in oral potentially malignant disorders (OPMDs) remains limited. Our study inve...

Biocontrol of rusted root rot in Panax ginseng by a combination of extracts from Bacillus amyloliquefaciens YY8 crude protein and Enterobacteriaceae YY115 ethyl acetate

Rusted root rot is one of the most common root diseases in Panax ginseng , and Cylindrocarpon destructans is one of the main pathogenic fungus. The objective of this study was to screen and explore the extracts of...

Molecular investigation of Blastocystis in children and calves in Bangladesh

Blastocystis , a widely distributed zoonotic protozoan infecting both humans and numerous animals, remains poorly understood with its potential medical and veterinary significance. This study examined the molecula...

Metagenomic mining of two Egyptian Red Sea sponges associated microbial community

The Red Sea is a promising habitat for the discovery of new bioactive marine natural products. Sponges associated microorganisms represent a wealthy source of compounds with unique chemical structures and dive...

Development of RPA-Cas12a assay for rapid and sensitive detection of Pneumocystis jirovecii

Pneumocystis jirovecii is a prevalent opportunistic fungal pathogen that can lead to life-threatening Pneumocystis pneumonia in immunocompromised individuals. Given that timely and accurate diagnosis is essential...

Structural and functional bacterial biodiversity in a copper, zinc and nickel amended bioreactor:  shotgun metagenomic study

At lower concentrations copper (Cu), zinc (Zn) and nickel (Ni) are trace metals essential for some bacterial enzymes. At higher concentrations they might alter and inhibit microbial functioning in a bioreactor...

Downregulation of Klebsiella pneumoniae RND efflux pump genes following indole signal produced by Escherichia coli

More than a century has passed since it was discovered that many bacteria produce indole, but research into the actual biological roles of this molecule is just now beginning. The influence of indole on bacter...

Alterations in the gut microbiota community are associated with childhood obesity and precocious puberty

To explore the distribution and differences in the intestinal microbiota in girls with obesity-related precocious puberty and the relationship between intestinal microbiota and obesity-related precocious puberty.

In vitro characterization of probiotic potential of Lactobacillus plantarum CM49 against selected cattle mastitogens

Bovine mastitis results in significant economic losses for the dairy industry globally due to milk production losses and decreased herd efficiency. This research aimed to isolate, select, and characterize indi...

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Trends in Microbiology is pleased to present a collection of articles from 2021 which highlight rapidly growing trends from different spheres of microbiology. These articles cover a range of topics including the future of prebiotics and probiotics; how microbial genomics has evolved over the last couple of decades; the durability of immune responses to SARS-CoV-2; the role that MAIT cells play in antimicrobial resistance and much more. We hope that you find this collection an enjoyable read and welcome any questions that you might have to [email protected]

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A Radical Reimagining of Fungal Two-Component Regulatory Systems

• Robert B. Bourret
• Emily N. Kennedy
• Clay A. Foster
• Victoria E. Sepúlveda
• William E. Goldman
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Durability of Immunity to SARS-CoV-2 and Other Respiratory Viruses

• Matthew K. Siggins
• Ryan S. Thwaites
• Peter J.M. Openshaw

Bacterial Coinfections in Coronavirus Disease 2019

• Lars F. Westblade
• Matthew S. Simon
• Michael J. Satlin

Interferon system deficiencies exacerbating severe pandemic virus infections

• Silke Stertz
• Benjamin G. Hale

Microbial Regulation of Host Physiology by Short-chain Fatty Acids

• Bart van der Hee
• Jerry M. Wells

High-specificity local and global c-di-GMP signaling

• Regine Hengge

Inorganic polyphosphate in host and microbe biology

• Marvin Q. Bowlin
• Michael J. Gray

Shaping the Future of Probiotics and Prebiotics

• Marla Cunningham
• M. Andrea Azcarate-Peril
• Alan Barnard
• Valerie Benoit
• Roberta Grimaldi
• Denis Guyonnet

Impact of Type I Interferons on Susceptibility to Bacterial Pathogens

• Adeline Peignier
• Dane Parker

Evolution of Microbial Genomics: Conceptual Shifts over a Quarter Century

• Eugene V. Koonin
• Kira S. Makarova
• Yuri I. Wolf

Emerging Role for MAIT Cells in Control of Antimicrobial Resistance

• Edwin Leeansyah
• Caroline Boulouis
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Type VII Toxin/Antitoxin Classification System for Antitoxins that Enzymatically Neutralize Toxins

• Xiaoxue Wang
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• Yi-Cheng Sun
• Thomas K. Wood

How Microbes Evolved to Tolerate Oxygen

• Maryam Khademian
• James A. Imlay

The Molecular Language of the Cnidarian–Dinoflagellate Symbiosis

• Sabrina L. Rosset
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Border Control: Regulating LPS Biogenesis

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Turning microbiome research into a force for health

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The microbiome comprises trillions of microorganisms living on and inside each of us. Historically, researchers have only guessed at its role in human health, but in the last decade or so, genetic sequencing techniques have illuminated this galaxy of microorganisms enough to study in detail.

As researchers unravel the complex interplay between our bodies and microbiomes, they are beginning to appreciate the full scope of the field’s potential for treating disease and promoting health.

For instance, the growing list of conditions that correspond with changes in the microbes of our gut includes type 2 diabetes, inflammatory bowel disease, Alzheimer’s disease, and a variety of cancers.

“In almost every disease context that’s been investigated, we’ve found different types of microbial communities, divergent between healthy and sick patients,” says professor of biological engineering Eric Alm. “The promise [of these findings] is that some of those differences are going to be causal, and intervening to change the microbiome is going to help treat some of these diseases.”

Alm’s lab, in conjunction with collaborators at the Broad Institute of MIT and Harvard, did some of the early work characterizing the gut microbiome and showing its relationship to human health. Since then, microbiome research has exploded, pulling in researchers from far-flung fields and setting new discoveries in motion. Startups are now working to develop microbiome-based therapies, and nonprofit organizations have also sprouted up to ensure these basic scientific advances turn into treatments that benefit the maximum number of people.

 “The first chapter in this field, and our history, has been validating this modality,” says Mark Smith PhD ’14, a co-founder of OpenBiome, which processes stool donations for hospitals to conduct stool transplants for patients battling gut infection. Smith is also currently CEO of the startup Finch Therapeutics, which is developing microbiome-based treatments. “Until now, it’s been about the promise of the microbiome. Now I feel like we’ve delivered on the first promise. The next step is figuring out how big this gets.”

An interdisciplinary foundation

MIT’s prominent role in microbiome research came, in part, through its leadership in a field that may at first seem unrelated. For decades, MIT has made important contributions to microbial ecology, led by work in the Parsons Laboratory in the Department of Civil and Environmental Engineering and by scientists including Institute Professor Penny Chisholm.

Ecologists who use complex statistical techniques to study the relationships between organisms in different ecosystems are well-equipped to study the behavior of different bacterial strains in the microbiome.

Not that ecologists — or anyone else — initially had much to study involving the human microbiome, which was essentially a black box to researchers well into the 2000s. But the Human Genome Project led to faster, cheaper ways to sequence genes at scale, and a group of researchers including Alm and visiting professor Martin Polz began using those techniques to decode the genomes of environmental bacteria around 2008.

Those techniques were first pointed at the bacteria in the gut microbiome as part of the Human Microbiome Project, which began in 2007 and involved research groups from MIT and the Broad Institute.

Alm first got pulled into microbiome research by the late biological engineering professor David Schauer as part of a research project with Boston Children’s Hospital. It didn’t take much to get up to speed: Alm says the number of papers explicitly referencing the microbiome at the time could be read in an afternoon.

The collaboration, which included Ramnik Xavier, a core institute member of the Broad Institute, led to the first large-scale genome sequencing of the gut microbiome to diagnose inflammatory bowel disease. The research was funded, in part, by the Neil and Anna Rasmussen Family Foundation.

The study offered a glimpse into the microbiome’s diagnostic potential. It also underscored the need to bring together researchers from diverse fields to dig deeper.

Taking an interdisciplinary approach is important because, after next-generation sequencing techniques are applied to the microbiome, a large amount of computational biology and statistical methods are still needed to interpret the resulting data — the microbiome, after all, contains more genes than the human genome. One catalyst for early microbiome collaboration was the Microbiology Graduate PhD Program, which recruited microbiology students to MIT and introduced them to research groups across the Institute.

As microbiology collaborations increased among researchers from different department and labs, Neil Rasmussen, a longtime member of the MIT Corporation and a member of the visiting committees for a number of departments, realized there was still one more component needed to turn microbiome research into a force for human health.

“Neil had the idea to find all the clinical researchers in the [Boston] area studying diseases associated with the microbiome and pair them up with people like [biological engineers, mathematicians, and ecologists] at MIT who might not know anything about inflammatory bowel disease or microbiomes but had the expertise necessary to solve big problems in the field,” Alm says.

In 2014, that insight led the Rasmussen Foundation to support the creation of the Center for Microbiome Informatics and Therapeutics (CMIT), one of the first university-based microbiome research centers in the country. CMIT is based at the MIT Institute for Medical Engineering and Science (IMES).

Tami Lieberman, the Hermann L. F. von Helmholtz Career Development Professor at MIT, whose background is in ecology, says CMIT was a big reason she joined MIT’s faculty in 2018. Lieberman has developed new genomic approaches to study how bacteria mutate in healthy and sick individuals, with a particular focus on the skin microbiome.

Laura Kiessling, a chemist who has been recognized for contributions to our understanding of cell surface interactions, was also quick to join CMIT. Kiessling, the Novartis Professor of Chemistry, has made discoveries relating to microbial mechanisms that influence immune function. Both Lieberman and Kiessling are also members of the Broad Institute.

Today, CMIT, co-directed by Alm and Xavier, facilitates collaborations between researchers and clinicians from hospitals around the country in addition to supporting research groups in the area. That work has led to hundreds of ongoing clinical trials that promise to further elucidate the microbiome’s connection to a broad range of diseases.

Fulfilling the promise of the microbiome

Researchers don’t yet know what specific strains of bacteria can improve the health of people with microbiome-associated diseases. But they do know that fecal matter transplants, which carry the full spectrum of gut bacteria from a healthy donor, can help patients suffering from certain diseases.

The nonprofit organization OpenBiome, founded by a group from MIT including Smith and Alm, launched in 2012 to help expand access to fecal matter transplants by screening donors for stool collection then processing, storing, and shipping samples to hospitals. Today OpenBiome works with more than 1,000 hospitals, and its success in the early days of the field shows that basic microbiome research, when paired with clinical trials like those happening at CMIT, can quickly lead to new treatments.

“You start with a disease, and if there’s a microbiome association, you can start a small trial to see if fecal transplants can help patients right away,” Alm explains. “If that becomes an effective treatment, while you’re rolling it out you can be doing the genomics to figure out how to make it better. So you can translate therapeutics into patients more quickly than when you’re developing small-molecule drugs.”

Another nonprofit project launched out of MIT, the Global Microbiome Conservancy, is collecting stool samples from people living nonindustrialized lifestyles around the world, whose guts have much different bacterial makeups and thus hold potential for advancing our understanding of host-microbiome interactions.

A number of private companies founded by MIT alumni are also trying to harness individual microbes to create new treatments, including, among others, Finch Therapeutics founded by Mark Smith; Concerto Biosciences, co-founded by Jared Kehe PhD ’20 and Bernardo Cervantes PhD ’20; BiomX, founded by Associate Professor Tim Lu; and Synlogic, founded by Lu and Jim Collins, the Termeer Professor of Medical Engineering and Science at MIT.

“There’s an opportunity to more precisely change a microbiome,” explains CMIT’s Lieberman. “But there’s a lot of basic science to do to figure out how to tweak the microbiome in a targeted way. Once we figure out how to do that, the therapeutic potential of the microbiome is quite limitless.”

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The biological sciences have a new leader in Richard Harland. Read his first interview as dean.

On September 18, the Division of Biological Sciences announced that Richard Harland would be its new dean following Michael Botchan’s well-deserved retirement. Harland is a professor of molecular and cell biology and the senior associate dean during Botchan’s deanship. Harland previously served two stints as chair of the Department of Molecular and Cell Biology and head of the Division of Genetics, Genomics, Evolution, and Development. Four decades after arriving at UC Berkeley as a new faculty member, Harland remains fascinated by embryos, evolution, and early developmental biology. There is, of course, a lot of fascinating research at UC Berkeley to keep his interest! In his first public interview as dean, Harland explained why he came to Berkeley, what it takes to enable top-tier research, how the division serves the state, and what pulled him away from his beloved lab to take on a leadership role.

What drew you to your area of developmental molecular biology?

When I was an undergraduate, I took courses with two amazing developmental biologists. Peter Lawrence worked on developmental genetics with flies. The other was John Gurdon, who won the Nobel Prize for showing how cells can be reprogrammed from a differentiated state back to the naive state. They both had extraordinarily clear and experiment-based lecturing styles. Rather than trying to load us up with facts, they taught us how all the experiments were done, and this just fascinated me. So I decided to go into the field of developmental biology. In fact, it was even better than I thought because I found that I loved doing experiments — being in the lab, hanging around smart people, and learning from them. Initially, when I joined the lab, I thought I would be working 9-to-5, but instead I spent long days there because it was so much fun. I have always loved looking at embryos and how their genes are expressed. It is extraordinarily beautiful to see how that single egg cleaves and generates an embryo. That has continued to captivate me. I did my thesis on DNA replication control, then went on to a postdoc position in Seattle and continued working with frogs and frog eggs. The recombinant DNA revolution made so many things possible. We could do so much to analyze where genes are expressed, and how their protein products work, but now with CRISPR, one can do all kinds of experiments that one would never have dreamed of to find out how early development works. It's been a real privilege to be involved in that field.

You have served as division head, department chair, senior associate dean, and now dean. What is your approach to leadership?

My role model is Max Perutz, who was the director of the Medical Research Council Lab at Cambridge, where I did my Ph.D. The lab is famous — it was often called a Nobel factory. His formula for success was to hire good people, give them what they need to do their best work, provide an environment where they will interact, and let them get on with it. My approach has been one of consensus building. I like to have people raise their ideas and discuss them. I don't like to impose. One of the best compliments I had as chair was that I have a light touch. That fits very well with the Berkeley ethos of shared governance. We have terrific faculty and excellent staff; as long as people are working towards some common good, things work out pretty well.

Richard Harland became the dean of biological sciences on July 1, 2024. (Photo by Johnny Gan Chong for UC Berkeley)

I had the option to go back to England and have a small lab, but I thought the possibilities here were much greater. It's a wonderful environment. I loved meeting the brilliant biologists on the faculty. The students are fantastic. Richard Harland

Were there any especially challenging or rewarding projects you handled as senior associate dean?

Renovations have been the most challenging projects. They can be very complex. It's easy to get delayed at many stages. I was involved in a complex project to renovate the basement labs in Weill Hall for increased use of zebrafish, and it was moving very slowly. The faculty and I got involved in the meetings so that the people who were affected by the project were making sure that things moved along and that there were solutions. In collaboration with several offices and committees, we figured out how to rearrange and build those facilities. That's still in progress. There are always new projects and major renovations, usually when we recruit new faculty. If they're moving into an older lab, then that lab needs to be brought up to standard. Some faculty have special needs, so we need to identify and renovate spaces for them. We have projects to install aquaria for studying corals and their symbiosis with algae for a new recruit. It was very effective to interact with Capital Projects to identify measures that could save money. For instance, our staff found extra circuits that were not being used so we didn't have to install a new electrical system from the outside. One has to have familiarity with the buildings. Working together like that makes sure we complete necessary projects as quickly as possible.

Richard Harland in his Durant Hall office (Photo by Johnny Gan Chong for UC Berkeley)

What is an exciting field where the division is growing?

We have a brand new Department of Neuroscience and a new Division of Molecular Therapeutics in the Department of Molecular and Cell Biology. There has also been amazing progress in evolutionary biology. Several of our own faculty have been studying human migrations by looking at DNA. The insights have been extraordinary in understanding our evolution and the evolution of animals. One of the highlights of the last year was the work of Daniel Rokhsar, who has spearheaded work on how the arrangements of chromosomes has not changed much in the last 600 million years. You can see stretches of the chromosomes where the same genes are present from anything from a sea anemone to a human. He used that pattern to place some of the most primitive animals on the phylogenetic tree in an authoritative way that was not possible before. DNA has been the clue to all sorts of levels of evolution but in terms of the evolution of vertebrate populations, this is where ancient DNA sequencing will be helpful. Berkeley will need to build a special lab to handle ancient DNA. We have the expertise to analyze these sequences but not the facilities to generate data. The danger of contamination with the environment is severe, so these have to be very clean labs. I’m putting my attention on finding the right place that doesn't have too much DNA floating around.

How are you supporting cutting-edge research and education?

The model is that we aim to provide the facilities, get the funding for the instrumentation, have an excellent graduate student program, recruit the best people, and provide an environment where great science can be done. For student education, although one can get a good, insightful worldview from lectures, if you really want to understand how science is done and how we know what we know, you have to understand how to set parameters, design tests, and evaluate results. Many of us want the opportunity for our undergraduates to get that kind of capstone experiment experience with lab research. We have so many talented undergraduates, it's very hard to provide that opportunity — and of course, everything costs money. I'm particularly proud of the efforts of my lab’s postdocs to establish a mini-course to introduce undergraduates to lab research and take them through live exercises with the potential for discovery. This bootcamp was funded by the department so we could hire undergraduates to help teach the course. I was trying to set up a self-sustaining system where the senior undergrads would train junior undergrads with help from postdocs. It is very important to figure out how we can give that kind of experiment experience and set up a model that other labs can work from.

How is the division maintaining its excellent graduate student program?

We have the built-in advantage of living in a wonderful area. People want to come and live here. Couples can both find work. With that and the excellence of Berkeley, we attract brilliant graduate students. The other aspect is, of course, funding. The state contributes about 12% of UC Berkeley’s operating budget. However, there are limits on the levers we can pull to fulfill our funding needs. There are requirements to increase class size and constraints on raising tuition. Californians have to actively prioritize higher education through bond measures. There has been a big change lately with the increase in salaries for graduate students and postdocs, which makes it possible to live in the area. The cost of personnel has far outpaced the amount of grant money that we can get from the federal government, so we tend to operate with smaller labs and a slightly smaller graduate program. It's too small. We have the ability to train excellent people, so this is a puzzle we are actively trying to solve. One of my main priorities is to help to raise money for the graduate program.

What are your other priorities for the 2024-25 academic year?

I want to continue those impressive and effective projects that Mike Botchan initiated. One is to improve the diversity of our faculty and students so that we can serve the state. I believe very strongly that this university exists to serve the state, and I think we do a great job providing an economic engine by training people who go into the workforce and make California what it is. Previously, as division head and department chair, our major emphasis was to improve the representation of women on faculty. I'm quite proud of the progress we made together. We may not have parity yet, but the sign of our success is that all of our prominent women have been subject to recruitment attempts from peer institutions, and in almost every case, we've managed to retain them. There's still some distance to go; we need to address the loss of women at the postdoctoral stage of their career. These efforts must apply to other kinds of diversity as well, where we need to seize the opportunities we can to hire people with underrepresented backgrounds.

What originally attracted you to UC Berkeley?

At the simplest level, I was offered a job here. I had the option to go back to England and have a small lab, but I thought the possibilities here were much greater. It's a wonderful environment. I loved meeting the brilliant biologists on the faculty. The students are fantastic. I love this place. That's one of the reasons I do these administrative jobs. No one's going to be remembered for administration, but if we can help the whole enterprise along, then that's a really satisfying process.

No one's going to be remembered for administration, but if we can help the whole enterprise along, then that's a really satisfying process. Richard Harland

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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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• criminal justice

1 year after end of cash bail in IL, early research shows impact less than many hoped or feared

Law enforcement officials continue to weigh pros, cons of legislation

CHICAGO -- One year after Illinois became the first state in the nation to eliminate the use of cash bail, the impact on the state's criminal justice system appears to have been far less dramatic than people on either side of the debate had predicted.

That, at least, is the early indication from an analysis of data being monitored by the Center for Criminal Justice at Loyola University in Chicago.

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"Jail populations did go down a bit, but nowhere near as much as some people were predicting, and the research suggests that the rate at which people are being released from jail pretrial likely hasn't changed dramatically," David Olson, a co-director of the center, said during an interview this week.

"What's changing is that the means of release are changing," he added. "People don't have to post the money, and rather than being released in a few days when they come up with the money, they're being released in a day or two."

The law to end cash bail in Illinois passed the General Assembly during a special lame duck session in January 2021. Known as the Pretrial Fairness Act, it was part of a broader criminal justice reform package known as the SAFE-T Act that was backed by the Legislative Black Caucus.

Those measures passed during a period of social unrest that followed the killing of George Floyd at the hands of Minneapolis police the previous summer. But the push to reform the cash bond system in Illinois had begun years earlier.

In 2017, the Illinois Supreme Court formed a Commission on Pretrial Practices, charging it with studying and making recommendations about comprehensive pretrial reform. That commission issued a report in April 2020, a full month before Floyd's murder.

In that report, the commission noted there was already a "growing national movement" underway focused on eliminating cash bail as a means of securing a defendant's appearance in court because it resulted in people being detained in jail, sometimes for lengthy periods of time while awaiting trial, solely because of their inability to pay a cash bond.

The report called for a new pretrial system in which only people charged with specific violent offenses would be held while awaiting trial. It further recommended detention only if prosecutors could show they posed an "unmanageable level of risk" that they would commit more offenses while on release and that no conditions or set of conditions could be attached to their release that would mitigate that risk.

The law passed the General Assembly on Jan. 13, 2021. Gov. JB Pritzker signed it into law Feb. 22, prompting a flurry of lawsuits in circuit courts throughout the state by county sheriffs and state's attorneys who challenged its constitutionality.

In December 2022, Pritzker signed an amendment to the original law that clarified which individuals and what crimes would be eligible for detention.

Then, just before the law was set to go into effect later that month, the Supreme Court put it on hold while it considered those challenges. But in a 5-2 ruling in July 2023, the court rejected those challenges, upheld the law as constitutional, and cleared the way for it to go into effect 60 days later, on Sept. 18, 2023 .

In advance of the one-year anniversary of the new law, the Center for Criminal Justice released preliminary data from its ongoing effort to monitor the law's impact.

One of the first things researchers noticed, Olson said, is that detention hearings now take considerably more time than they used to. In urban counties that handle large numbers of criminal cases, he said, the median length of a detention hearing went from four minutes before the law took effect to 16 minutes under the new rules.

Researchers also noticed a change in the issues discussed during those hearings. Prior to the new law, Olson said, most of the discussion centered on the offense being charged and the defendant's criminal history. But since the new law went into effect, he said there is more focus on the strength of the evidence against the defendant as well as the risk the defendant poses to other individuals.

Also, he said, judges have begun providing more specific, detailed explanations for their decisions about whether to hold a defendant or place conditions on their release.

"Part of that is likely because this is a new law," he said. "There are a lot of legal challenges on individual cases as to whether or not the person should have been detained, and it's likely the judges are trying to establish a clear record for those subsequent appeals. But part of it is also that the expectations of what is considered during the decision to detain are much more clearly articulated in the law, and the judge is likely trying to ensure that they kind of touch on all those things that have to be considered."

But one issue that no longer comes up during detention hearings, he said, is money.

"Prior to the law going into effect, statewide about $140 million each year was paid by defendants in the form of posting money to secure their pretrial release," he said. "No longer are they posting money to secure their pretrial release. So, $140 million is now remaining in the community."

Meanwhile, Olson said, the research so far has not shown any significant change in the percentage of people who fail to appear for subsequent court hearings. Prior to the new law, he said, the failure-to-appear rate hovered around 17 percent, and since the law took effect it has been "statistically very similar," at about 15 percent.

In addition, he said, the research so far has not documented any increase in crime as a result of defendants being released without posting bond.

"We can't say whether it's had an impact on crime," Olson said. "But what we can say is, during the first six months of 2023 compared to the first six months of 2024, crime is not up in Illinois. It's not up in Chicago. It's not up in other urban areas. It's not up in rural areas. It's not up for violent crime. It's not up for property crime."

Olson emphasized that the findings so far are only preliminary because the law is still new and many of the most serious criminal cases that have been filed in the last year are still working their way through the court system.

But he said the research so far does appear to indicate that the basic theory behind the old cash bail system - that requiring someone to post a bond was necessary to protect public safety and secure a defendant's later appearance in court - was fundamentally flawed.

"There's plenty of empirical evidence that suggests that people posting money isn't what guaranteed them showing up to court," he said. "And part of it is to recognize where the money that they are posting comes from. It's usually not the defendant's money. It's their family's money."

He noted money used to post bail was often never returned to the defendant under the previous system.

"And also the threat of losing your money if you don't show up - for many defendants, they realize that they're not going to see that money ever again, that if they're convicted, that money is going to be used to pay fines and fees, all of which can still be imposed by the by the court," he said.

Some lawmakers and advocates gathered Wednesday morning to mark the anniversary.

Cook County Board President Toni Preckwinkle was among those celebrating the implementation of the Pretrial Fairness Act.

She said for too long people were jailed simply because they didn't have the money to buy their freedom.

Others are not thrilled with elements of the law.

Kane County Sheriff Ron Hain said it has strained the court system by increasing caseloads.

DuPage County State's Attorney Bob Berlin wants to see the law changed to give judges discretion to detain defendants charged with certain crimes.

Berlin was initially a critic, but pushed for modifications to cashless bail provisions before the law took effect.

"Overall, I think the law is working fairly well," he said.

Berlin said he would like Illinois adopt the model for pre-trial fairness used by New Jersey.

"Their law provides judges with discretion in almost every single felony to detain someone if they're a threat to the community, threat to intimidate witnesses or a threat to obstruct justice," Berlin said.

Lake County State's Attorney Eric Rinehart supported the criminal reform bill, and said it's led to a decrease in violent crime.

"The SAFE-T Act is making sure that those with access to cash can't simply use their cash to get out at 2 a.m. and harm someone they just harmed," Rinehart said.

Cook County public defender Sharone Mitchell said some lawmakers launched a fearmongering campaign that a cashless system would lead to criminals flooding the streets.

"You saw state's attorneys across the state, some sheriffs, really predict that there was going to be chaos, that there would be a purge, and no one would come to court," Mitchell said.

Whether lawmakers call for continued adjustments, they say the act makes public safety a priority.

ABC7 Chicago's Karen Jordan contributed to this report.

Capitol News Illinois is a nonprofit, nonpartisan news service covering state government. It is distributed to hundreds of print and broadcast outlets statewide. It is funded primarily by the Illinois Press Foundation and the Robert R. McCormick Foundation, along with major contributions from the Illinois Broadcasters Foundation and Southern Illinois Editorial Association.

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