Acquired interbacterial defense systems protect against interspecies antagonism in the human gut microbiome

Mapping Intimacies ◽

10.1101/471110 ◽

2018 ◽

Cited By ~ 1

Author(s):

Benjamin D. Ross ◽

Adrian J. Verster ◽

Matthew C. Radey ◽

Danica T. Schmidtke ◽

Christopher E. Pope ◽

...

Keyword(s):

Gut Microbiome ◽

Gene Clusters ◽

Protective Capacity ◽

Human Gut ◽

Microbiome Composition ◽

Toxin Resistance ◽

Human Gut Microbiome ◽

Bacterial Antagonism ◽

The Impact

AbstractThe impact of direct interactions between co-resident microbes on microbiome composition is not well understood. Here we report the occurrence of acquired interbacterial defense (AID) gene clusters in bacterial residents of the human gut microbiome. These clusters encode arrays of immunity genes that protect against type VI secretion toxin-mediated intra- and inter-species bacterial antagonism. Moreover, the clusters reside on mobile elements and we demonstrate that their transfer is sufficient to confer toxin resistance in vitro and in gnotobiotic mice. Finally, we identify and validate the protective capacity of a recombinase-associated AID subtype (rAID-1) present broadly in Bacteroidales genomes. These rAID-1 gene clusters have a structure suggestive of active gene acquisition and include predicted immunity factors of toxins deriving from diverse organisms. Our data suggest that neutralization of contact-dependent interbacterial antagonism via AID systems shapes human gut microbiome ecology.

Lacticaseibacillus rhamnosus GG and Saccharomyces cerevisiae boulardii supplementation exert protective effects on human gut microbiome following antibiotic administration in vitro

Beneficial Microbes ◽

10.3920/bm2020.0180 ◽

2021 ◽

pp. 1-16

Author(s):

C. Duysburgh ◽

P. Van den Abbeele ◽

M. Morera ◽

M. Marzorati

Keyword(s):

Saccharomyces Cerevisiae ◽

Gut Microbiome ◽

Gastrointestinal Symptoms ◽

Lactobacillus Rhamnosus ◽

Antibiotic Administration ◽

Protective Effects ◽

Human Gut ◽

Human Gut Microbiome ◽

The Impact

Antibiotic-induced dysbiosis of the microbial community has been associated with several gastrointestinal symptoms. The impact of repeated administration of Lacticaseibacillus rhamnosus GG (CNCM-I-4798) (formerly known as Lactobacillus rhamnosus GG), Saccharomyces cerevisiae boulardii (CNCM-I-1079) and their combination (associated in Smebiocta/Smectaflora Protect®) in supporting recovery of gut microbiota functionality and composition during and following amoxicillin:clavulanic acid administration was evaluated in vitro. Antibiotic dosage negatively affected SCFA production, coinciding with detrimental effects on Bacteroidetes, Firmicutes and Bifidobacterium spp. in the simulated proximal colon, while Akkermansia muciniphila was significantly reduced in the distal colon. L. rhamnosus GG and S. boulardii were able to thrive in both colon regions upon dosing, with S. boulardii even showing protective effects on the survival of L. rhamnosus GG during antibiotic administration. The impact of the probiotic strains on microbiome recovery revealed that supplementation with L. rhamnosus GG and/or S. boulardii resulted in a stimulating effect on the most abundant bacterial groups within the bacterial community of each donor. For one of the donors tested, co-dosing of L. rhamnosus GG and S. boulardii resulted in superior short-chain fatty acid recovery accompanied by a stronger increase in abundance of Bifidobacteriaceae. Overall, the current study provides first evidence that combined supplementation of L. rhamnosus GG and S. boulardii might be an interesting candidate in limiting detrimental effects of amoxicillin:clavulanic acid on the human gut microbiome, though further studies are warranted to confirm these findings.

Examining the Effects of an Anti-Salmonella Bacteriophage Preparation, BAFASAL®, on Ex-Vivo Human Gut Microbiome Composition and Function Using a Multi-Omics Approach

Viruses ◽

10.3390/v13091734 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1734

Author(s):

Janice Mayne ◽

Xu Zhang ◽

James Butcher ◽

Krystal Walker ◽

Zhibin Ning ◽

...

Keyword(s):

Food Chain ◽

Gut Microbiome ◽

Food Industry ◽

Ex Vivo ◽

Human Gut ◽

Microbiome Composition ◽

Human Gut Microbiome ◽

And Function ◽

The Impact

Salmonella infections (salmonellosis) pose serious health risks to humans, usually via food-chain contamination. This foodborne pathogen causes major food losses and human illnesses, with significant economic impacts. Overuse of antibiotics in the food industry has led to multidrug-resistant strains of bacteria, and governments are now restricting their use, leading the food industry to search for alternatives to secure food chains. Bacteriophages, viruses that infect and kill bacteria, are currently being investigated and used as replacement treatments and prophylactics due to their specificity and efficacy. They are generally regarded as safe alternatives to antibiotics, as they are natural components of the ecosystem. However, when specifically used in the industry, they can also make their way into humans through our food chain or exposure, as is the case for antibiotics. In particular, agricultural workers could be repeatedly exposed to bacteriophages supplemented to animal feeds. To our knowledge, no studies have investigated the effects of such exposure to bacteriophages on the human gut microbiome. In this study, we used a novel in-vitro assay called RapidAIM to investigate the effect of a bacteriophage mixture, BAFASAL®, used in poultry farming on five individual human gut microbiomes. Multi-omics analyses, including 16S rRNA gene sequencing and metaproteomic, revealed that ex-vivo human gut microbiota composition and function were unaffected by BAFASAL® treatment, providing an additional measure for its safety. Due to the critical role of the gut microbiome in human health and the known role of bacteriophages in regulation of microbiome composition and function, we suggest assaying the impact of bacteriophage-cocktails on the human gut microbiome as a part of their safety assessment.

Examining the effects of an anti-Salmonella bacteriophage preparation, BAFASAL, on ex vivo human gut microbiome composition and function using a multi-omics approach

10.1101/2021.07.04.451072 ◽

2021 ◽

Author(s):

Janice Mayne ◽

Xu Zhang ◽

James Butcher ◽

Krystal Walker ◽

Zhibin Ning ◽

...

Keyword(s):

Food Chain ◽

Gut Microbiome ◽

Ex Vivo ◽

Human Gut ◽

Microbiome Composition ◽

Human Gut Microbiome ◽

Salmonella Infections ◽

And Function ◽

The Impact

Salmonella infections (salmonellosis) pose serious health risks to humans, usually via contamination in our food chain. This foodborne pathogen causes major food losses and human illnesses that result in significant economic impacts. Pathogens such as Salmonella have traditionally been kept at bay through the use of antibiotics, but antibiotic overuse within the food industry has led to the development of numerous multidrug-resistant bacterial strains. Thus, governments are now restricting antibiotic use, forcing the industry to search for alternatives to secure safe food chains. Bacteriophages, viruses that infect and kill bacteria, are currently being investigated and used as replacement treatments and prophylactics due to their specificity and efficacy. They are generally regarded as safe alternatives to antibiotics as they are natural components of the ecosystem. One example is BAFASEL, a commercial bacteriophage mixture that specifically targets Salmonella and is currently approved for use in poultry farming. However, when specifically used in the industry they can also make their way into humans through our food chain or exposure as is the case for antibiotics. In particular, agricultural workers could be repeatedly exposed to bacteriophages supplemented in animal feeds. To the best of our knowledge, no studies have investigated the effects of such exposure to bacteriophages on the human gut microbiome. In this study, we used a novel in vitro assay called RapidAIM to investigate BAFASAL's potential impact on five individual human gut microbiomes. Multi-omics analyses, including 16S rRNA gene sequencing and metaproteomic, revealed that ex vivo human gut microbiota composition and function were unaffected by BAFASAL treatment providing an additional measure for its safety. Due to the critical role of the gut microbiome in human health and the known role of bacteriophages in regulation of microbiome composition and function, we suggest assaying the impact of bacteriophage-cocktails on the human gut microbiome as a part of their safety assessment.

Taxonomic signatures of cause-specific mortality risk in human gut microbiome

Nature Communications ◽

10.1038/s41467-021-22962-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Aaro Salosensaari ◽

Ville Laitinen ◽

Aki S. Havulinna ◽

Guillaume Meric ◽

Susan Cheng ◽

...

Keyword(s):

Mortality Risk ◽

Gut Microbiome ◽

Human Gut ◽

Cross Sectional ◽

Microbiome Composition ◽

Human Gut Microbiome ◽

Non Invasive ◽

Sequencing Technologies

AbstractThe collection of fecal material and developments in sequencing technologies have enabled standardised and non-invasive gut microbiome profiling. Microbiome composition from several large cohorts have been cross-sectionally linked to various lifestyle factors and diseases. In spite of these advances, prospective associations between microbiome composition and health have remained uncharacterised due to the lack of sufficiently large and representative population cohorts with comprehensive follow-up data. Here, we analyse the long-term association between gut microbiome variation and mortality in a well-phenotyped and representative population cohort from Finland (n = 7211). We report robust taxonomic and functional microbiome signatures related to the Enterobacteriaceae family that are associated with mortality risk during a 15-year follow-up. Our results extend previous cross-sectional studies, and help to establish the basis for examining long-term associations between human gut microbiome composition, incident outcomes, and general health status.

Health and disease markers correlate with gut microbiome composition across thousands of people

Nature Communications ◽

10.1038/s41467-020-18871-1 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Ohad Manor ◽

Chengzhen L. Dai ◽

Sergey A. Kornilov ◽

Brett Smith ◽

Nathan D. Price ◽

...

Keyword(s):

Gut Microbiome ◽

Lifestyle Factors ◽

Clinical Markers ◽

Human Gut ◽

Microbiome Composition ◽

Targeted Interventions ◽

Human Gut Microbiome ◽

Host Diet ◽

Microbe Interactions ◽

Host Microbe Interactions

Abstract Variation in the human gut microbiome can reflect host lifestyle and behaviors and influence disease biomarker levels in the blood. Understanding the relationships between gut microbes and host phenotypes are critical for understanding wellness and disease. Here, we examine associations between the gut microbiota and ~150 host phenotypic features across ~3,400 individuals. We identify major axes of taxonomic variance in the gut and a putative diversity maximum along the Firmicutes-to-Bacteroidetes axis. Our analyses reveal both known and unknown associations between microbiome composition and host clinical markers and lifestyle factors, including host-microbe associations that are composition-specific. These results suggest potential opportunities for targeted interventions that alter the composition of the microbiome to improve host health. By uncovering the interrelationships between host diet and lifestyle factors, clinical blood markers, and the human gut microbiome at the population-scale, our results serve as a roadmap for future studies on host-microbe interactions and interventions.

A Pleiotropic Missense Variant in SLC39A8 Is Associated With Crohn’s Disease and Human Gut Microbiome Composition

Gastroenterology ◽

10.1053/j.gastro.2016.06.051 ◽

2016 ◽

Vol 151 (4) ◽

pp. 724-732 ◽

Cited By ~ 59

Author(s):

Dalin Li ◽

Jean-Paul Achkar ◽

Talin Haritunians ◽

Jonathan P. Jacobs ◽

Ken Y. Hui ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Gut Microbiome ◽

Missense Variant ◽

Human Gut ◽

Microbiome Composition ◽

Human Gut Microbiome

W1832 Diversity in Human Gut Microbiome Composition Assessed by Pyrosequencing: Comparison of Sampling Methods

Gastroenterology ◽

10.1016/s0016-5085(10)63452-x ◽

2010 ◽

Vol 138 (5) ◽

pp. S-749

Author(s):

James D. Lewis ◽

Gary D. Wu ◽

Ying-Yu Chen ◽

Christian Hoffmann ◽

Kyle Bittinger ◽

...

Keyword(s):

Gut Microbiome ◽

Sampling Methods ◽

Human Gut ◽

Microbiome Composition ◽

Human Gut Microbiome

Alterations in human gut microbiome composition and metabolism after exposure to glyphosate and Roundup and/or a spore-based formulation using the SHIME® technology

10.1101/2021.12.16.472928 ◽

2021 ◽

Author(s):

Robin Mesnage ◽

Marta Calatayud ◽

Cindy Duysburgh ◽

Massimo Marzorati ◽

Michael Antoniou

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Large Scale ◽

Epidemiological Studies ◽

Human Gut ◽

Microbiome Composition ◽

Human Gut Microbiome ◽

Ammonium Production ◽

Profiling Techniques ◽

Microbial Environment

Despite extensive research into the toxicology of the herbicide glyphosate, there are still major unknowns regarding its effects on the human gut microbiome. As a step in addressing this knowledge gap, we describe for the first time the effects of glyphosate and a Roundup glyphosate-based herbicide on infant gut microbiota using SHIME technology, which mimics the entire gastrointestinal tract. SHIME microbiota culture was undertaken in the presence of a concentration of 100 mg/L (corresponding to a dose of 1.6 mg/kg/day) glyphosate and the same glyphosate equivalent concentration of Roundup, which is in the range of the US chronic reference dose, and subjected to molecular profiling techniques to assess outcomes. Roundup and to a lesser extent glyphosate caused an increase in fermentation activity, resulting in acidification of the microbial environment. This was also reflected by an increase in lactate and acetate production concomitant to a decrease in the levels of propionate, valerate, caproate and butyrate. Ammonium production reflecting proteolytic activities was increased by Roundup exposure. Global metabolomics revealed large scale disturbances in metabolite profiles, including an increased abundance of long chain polyunsaturated fatty acids (n3 and n6). Although changes in bacterial composition measured by qPCR and 16S rRNA sequencing were less clear, our results suggested that lactobacilli had their growth stimulated as a result of microenvironment acidification. Co-treatment with the spore-based probiotic formulation MegaSporeBiotic reverted some of the changes in short-chain fatty acid levels. Altogether, our results suggest that glyphosate can exert effects on human gut microbiota at permitted regulatory levels of exposure, highlighting the need for epidemiological studies aimed at evaluating the effects of glyphosate herbicides on human gut microbiome function.

Quantifying the impact of Human Leukocyte Antigen on the human gut microbiome

10.1101/2020.01.14.907196 ◽

2020 ◽

Cited By ~ 2

Author(s):

Stijn P. Andeweg ◽

Can Keşmir ◽

Bas E. Dutilh

Keyword(s):

Immune System ◽

Gut Microbiome ◽

Human Leukocyte ◽

Human Gut ◽

Microbiome Composition ◽

Leukocyte Antigen ◽

Human Gut Microbiome ◽

Microbiome Diversity ◽

Human Immune ◽

Hla Molecules

AbstractObjectiveThe gut microbiome is affected by a number of factors, including the innate and adaptive immune system. The major histocompatibility complex (MHC), or the human leukocyte antigen (HLA) in humans, performs an essential role in vertebrate immunity, and is very polymorphic in different populations. HLA determines the specificity of T lymphocyte and natural killer (NK) cell responses, including against the commensal bacteria present in the human gut. Thus, it is likely that our HLA molecules and thereby the adaptive immune response, can shape the composition of our microbiome. Here, we investigated the effect of HLA haplotype on the microbiome composition.ResultsWe performed HLA typing and microbiota composition analyses on 3,002 public human gut microbiome datasets. We found that (i) individuals with functionally similar HLA molecules (i.e. presenting similar peptides) are also similar in their microbiota, and (ii) HLA homozygosity correlated with microbiome diversity, suggesting that diverse immune responses limit microbiome diversity.ConclusionOur results show a statistical association between host HLA haplotype and gut microbiome composition. Because the HLA haplotype is a readily measurable parameter of the human immune system, these results open the door to incorporating the immune system into predictive microbiome models.IMPORTANCEThe microorganisms that live in the digestive tracts of humans, known as the gut microbiome, are essential for hosts survival as they support crucial functions. For example, they support the host in facilitating the uptake of nutrients and give colonization resistance against pathogens. The composition of the gut microbiome varies among humans. Studies have proposed multiple factors driving the observed variation, including; diet, lifestyle, and health condition. Another major influence on the microbiome is the host’s genetic background. We hypothesized the immune system to be one of the most important genetic factors driving the differences observed between gut microbiomes. Therefore, we are interested in linking the polymorphic molecules that play a role in human immune responses to the composition of the microbiome. HLA molecules are the most polymorphic molecules in our genome and therefore makes an excellent candidate to test such an association/link. To our knowledge for the first time, our results indicate a significant impact of the HLA on the human gut microbiome composition.

Polyphenol utilization proteins in human gut microbiome

Applied and Environmental Microbiology ◽

10.1128/aem.01851-21 ◽

2021 ◽

Author(s):

Bo Zheng ◽

Yinchao He ◽

Pengxiang Zhang ◽

Yi-Xin Huo ◽

Yanbin Yin

Keyword(s):

Human Health ◽

Gut Microbiome ◽

Sequence Similarity ◽

Gene Clusters ◽

Metagenomic Data ◽

Human Populations ◽

Human Gut ◽

Systematic Classification ◽

Dietary Polyphenols ◽

Human Gut Microbiome

Dietary polyphenols can significantly benefit human health, but their bioavailability is metabolically controlled by human gut microbiota. To facilitate the study of polyphenol metabolism for human gut health, we have manually curated experimentally characterized polyphenol utilization proteins (PUPs) from published literature. This resulted in 60 experimentally characterized PUPs (named seeds) with various metadata, such as species and substrate. Further database search found 107,851 homologs of the seeds from UniProt and UHGP (Unified Human Gastrointestinal Protein) databases. All PUP seeds and homologs were classified into protein classes, families and subfamilies based on Enzyme Commission (EC) numbers, Pfam (protein family) domains and sequence similarity networks. By locating PUP homologs in the genomes of UHGP, we have identified 1,074 physically linked PUP gene clusters (PGCs), which are potentially involved in polyphenol metabolism in the human gut. The gut microbiome of Africans was consistently ranked the top in terms of the abundance and prevalence of PUP homologs and PGCs among all geographical continents. This reflects the fact that dietary polyphenols are more commonly consumed by African population than other populations such as Europeans and North Americans. A case study of the Hadza hunter-gatherer microbiome verified the feasibility of using dbPUP to profile metagenomic data for biologically meaningful discovery, suggesting an association between diet and PUP abundance. A Pfam domain enrichment analysis of PGCs identified a number of putatively novel PUP families. Lastly, a user-friendly web interface ( https://bcb.unl.edu/dbpup/ ) provides all the data online to facilitate the research of polyphenol metabolism for improved human health. Importance Long-term consumption of polyphenol-rich foods have been shown to lower the risk of various human diseases such as cardiovascular diseases, cancers, and metabolic diseases. Raw polyphenols are often enzymatically processed by gut microbiome, which encode various polyphenol utilization proteins (PUPs) to produce metabolites with much higher bioaccessibility to gastrointestinal cells. This study delivered dbPUP as an online database for experimentally characterized PUPs and their homologs in human gut microbiome. This work also performed a systematic classification of PUPs into enzyme classes, families, and subfamilies. The signature Pfam domains were identified for PUP families, enabling conserved domain-based PUP annotation. This standardized sequence similarity-based PUP classification system offered a guideline for the future inclusion of new experimentally characterized PUPs and the creation of new PUP families. An in-depth data analysis was further conducted on PUP homologs and physically linked PUP gene clusters (PGCs) in gut microbiomes of different human populations.