The Reactobiome Unravels a New Paradigm in Human Gut Microbiome Metabolism

AbstractChanges in microbial metabolism have been used as the main approach to assess function and elucidate environmental and host-microbiome interactions. This can be hampered by uncharacterised metagenome species and lack of metabolic annotation. To address this, we present a comprehensive computational platform for population stratification based on microbiome composition, the underlying metabolic potential and generation of metagenome species and community level metabolic models. We revisit the concepts of enterotype and microbiome richness introducing the reactobiome as a stratification method to unravel the metabolic features of the human gut microbiome. The reactobiome encapsulates resilience and microbiome dysbiosis at a functional level. We describe five reactotypes in healthy populations from 16 countries, with specific amino acid, carbohydrate and xenobiotic metabolic features. The validity of the approach was tested to unravel host-microbiome and environmental interactions by applying the reactobiome analysis on a one-year Swedish longitudinal cohort, integrating gut metagenomics, plasma metabolomics and clinical data.

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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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Global and temporal state of the human gut microbiome in health and disease

10.21203/rs.3.rs-339282/v1 ◽

2021 ◽

Author(s):

Saeed Shoaie ◽

Sunjae Lee ◽

Mathieu Almeida ◽

Gholamreza Bidkhori ◽

Nicolas Pons ◽

...

Keyword(s):

Gut Microbiome ◽

Integrative Analysis ◽

Human Gut ◽

Human Gut Microbiome ◽

Health And Disease ◽

One Year ◽

The Stability ◽

Clinical Phenotyping ◽

Sampling Times

Abstract The role of gut microbiota in humans is of great interest, and metagenomics provided the possibilities for extensively analysing bacterial diversity in health and disease. Here we explored the human gut microbiome samples across 19 countries, performing compositional, functional and integrative analysis. To complement these data and analyse the stability of the microbiome, we followed 86 healthy Swedish individuals over one year, with four sampling times and extensive clinical phenotyping. The integrative analysis of temporal microbiome changes shows the existence of two types of species with a tendency to vary in abundance with time, here called outflow and inflow species. Importantly, the former tends to be enriched in disease, while the latter is enriched in health. We suggest that the decrease of disease-associated outflow and the increase of health-associated inflow species with time may be a fundamental albeit previously unrecognized aspect of the homeostasis maintenance in a healthy microbiome.

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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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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.

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Interplay between the human gut microbiome and host metabolism

10.1101/561787 ◽

2019 ◽

Cited By ~ 1

Author(s):

Alessia Visconti ◽

Caroline I. Le Roy ◽

Fabio Rosa ◽

Niccolo Rossi ◽

Tiphaine C. Martin ◽

...

Keyword(s):

Gut Microbiome ◽

Metabolic Pathways ◽

Taxonomic Composition ◽

Metagenomic Sequencing ◽

Human Gut ◽

Metabolic Potential ◽

Microbial Ecosystem ◽

Microbiome Composition ◽

Shotgun Metagenomic Sequencing ◽

Key Species

AbstractThe human gut is inhabited by a complex and metabolically active microbial ecosystem regulating host health. While many studies have focused on the effect of individual microbial taxa, the metabolic potential of the entire gut microbial ecosystem has been largely under-explored. We characterised the gut microbiome of 1,004 twins via whole shotgun metagenomic sequencing (average 39M reads per sample). We observed greater similarity, across unrelated individuals, for functional metabolic pathways (82%) than for taxonomic composition (43%). We conducted a microbiota-wide association study linking both taxonomic information and microbial metabolic pathways with 673 blood and 713 faecal metabolites (Metabolon, Inc.). Metabolic pathways associated with 34% of blood and 95% of faecal metabolites, with over 18,000 significant associations, while species-level results identified less than 3,000 associations, suggesting that coordinated action of multiple taxa is required to affect the metabolome. Finally, we estimated that the microbiome mediated a crosstalk between 71% of faecal and 15% of blood metabolites, highlighting six key species (unclassified Subdoligranulum spp., Faecalibacterium prausnitzii, Roseburia inulinivorans, Methanobrevibacter smithii, Eubacterium rectale, and Akkermansia muciniphila). Because of the large inter-person variability in microbiome composition, our results underline the importance of studying gut microbial metabolic pathways rather than focusing purely on taxonomy to find therapeutic and diagnostic targets.

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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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