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

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.

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Large-scale association analyses identify host factors influencing human gut microbiome composition

Nature Genetics ◽

10.1038/s41588-020-00763-1 ◽

2021 ◽

Vol 53 (2) ◽

pp. 156-165

Author(s):

Alexander Kurilshikov ◽

Carolina Medina-Gomez ◽

Rodrigo Bacigalupe ◽

Djawad Radjabzadeh ◽

Jun Wang ◽

...

Keyword(s):

Gut Microbiome ◽

Large Scale ◽

Host Factors ◽

Human Gut ◽

Association Analyses ◽

Microbiome Composition ◽

Human Gut Microbiome ◽

Factors Influencing

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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.

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Flavonoid-Modifying Capabilities of the Human Gut Microbiome—An In Silico Study

Nutrients ◽

10.3390/nu13082688 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2688

Author(s):

Tobias Goris ◽

Rafael R. C. Cuadrat ◽

Annett Braune

Keyword(s):

Gut Microbiome ◽

Large Scale ◽

Health Impact ◽

Gut Bacteria ◽

Human Gut ◽

Positive Health ◽

Human Gut Microbiome ◽

Nutritional Recommendations ◽

Genes Encoding ◽

A Minor

Flavonoids are a major group of dietary plant polyphenols and have a positive health impact, but their modification and degradation in the human gut is still widely unknown. Due to the rise of metagenome data of the human gut microbiome and the assembly of hundreds of thousands of bacterial metagenome-assembled genomes (MAGs), large-scale screening for potential flavonoid-modifying enzymes of human gut bacteria is now feasible. With sequences of characterized flavonoid-transforming enzymes as queries, the Unified Human Gastrointestinal Protein catalog was analyzed and genes encoding putative flavonoid-modifying enzymes were quantified. The results revealed that flavonoid-modifying enzymes are often encoded in gut bacteria hitherto not considered to modify flavonoids. The enzymes for the physiologically important daidzein-to-equol conversion, well studied in Slackiaisoflavoniconvertens, were encoded only to a minor extent in Slackia MAGs, but were more abundant in Adlercreutzia equolifaciens and an uncharacterized Eggerthellaceae species. In addition, enzymes with a sequence identity of about 35% were encoded in highly abundant MAGs of uncultivated Collinsella species, which suggests a hitherto uncharacterized daidzein-to-equol potential in these bacteria. Of all potential flavonoid modification steps, O-deglycosylation (including derhamnosylation) was by far the most abundant in this analysis. In contrast, enzymes putatively involved in C-deglycosylation were detected less often in human gut bacteria and mainly found in Agathobacter faecis (formerly Roseburia faecis). Homologs to phloretin hydrolase, flavanonol/flavanone-cleaving reductase and flavone reductase were of intermediate abundance (several hundred MAGs) and mainly prevalent in Flavonifractor plautii. This first comprehensive insight into the black box of flavonoid modification in the human gut highlights many hitherto overlooked and uncultured bacterial genera and species as potential key organisms in flavonoid modification. This could lead to a significant contribution to future biochemical-microbiological investigations on gut bacterial flavonoid transformation. In addition, our results are important for individual nutritional recommendations and for biotechnological applications that rely on novel enzymes catalyzing potentially useful flavonoid modification reactions.

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Large-scale comparative metagenomics of Blastocystis, a common member of the human gut microbiome

The ISME Journal ◽

10.1038/ismej.2017.139 ◽

2017 ◽

Vol 11 (12) ◽

pp. 2848-2863 ◽

Cited By ~ 41

Author(s):

Francesco Beghini ◽

Edoardo Pasolli ◽

Tin Duy Truong ◽

Lorenza Putignani ◽

Simone M Cacciò ◽

...

Keyword(s):

Gut Microbiome ◽

Large Scale ◽

Human Gut ◽

Human Gut Microbiome ◽

Comparative Metagenomics

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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.

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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

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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

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Natural and after colon washing fecal samples: the two sides of the coin for investigating the human gut microbiome

10.1101/2021.06.29.450302 ◽

2021 ◽

Author(s):

Elisabetta Piancone ◽

Bruno Fosso ◽

Mariangela De Robertis ◽

Elisabetta Notario ◽

Annarita Oranger ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Digital Pcr ◽

Shannon Index ◽

Individual Variability ◽

Rrna Gene ◽

Human Gut ◽

Human Gut Microbiome ◽

Taxonomic Analysis ◽

Paired Samples

To date there are several studies focusing on the importance of gut microbiome for human health, however the selection of a universal sampling matrix representative of the microbial biodiversity associated to the gastrointestinal (GI) tract, still represents a challenge. Here we present a study in which, through a deep metabarcoding analysis of the 16S rRNA gene, we compared two sampling matrices, feces (F) and colonic lavage liquid (LL), in order to evaluate their accuracy to represent the complexity of the human gut microbiome. A training set of 37 volunteers was attained and paired F and LL samples were collected from each subject. A preliminary absolute quantification of total 16S rDNA, performed by droplet digital PCR (ddPCR), confirmed that sequencing and taxonomic analysis were performed on same total bacterial abundance obtained from the two sampling methods. The taxonomic analysis of paired samples revealed that, although specific taxa were predominantly or exclusively observed in LL samples, as well as other taxa were detectable only or were predominant in stool, the microbiomes of the paired samples F and LL in the same subject hold overlapping taxonomic composition. Moreover, LL samples revealed a higher biodiversity than stool at all taxonomic ranks, as demonstrated by the Shannon Index and the Inverse Simpson's Index. We also found greater inter-individual variability than intra-individual variability in both sample matrices. Finally, functional differences were unveiled in the gut microbiome detected in the F and LL samples. A significant overrepresentation of 22 and 13 metabolic pathways, mainly occurring in Firmicutes and Proteobacteria, was observed in gut microbiota detected in feces and LL samples, respectively. This suggests that LL samples may allow for the detection of microbes adhering to the intestinal mucosal surface as members of the resident flora that are not easily detectable in stool, most likely representative of a diet-influenced transient microbiota. This first comparative study on feces and LL samples for the study of the human gut microbiome demonstrates that the use of both types of sample matrices may represent a possible choice to obtain a more complete view of the human gut microbiota in response to different biological and clinical questions.

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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.

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