Trust Your Gut: The Human Gut Microbiome in Health and Disease

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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Role of Human Gut Microbiome in Health and Disease

Microbiome-Host Interactions ◽

10.1201/9781003037521-9 ◽

2021 ◽

pp. 101-112

Author(s):

Nazar Reehana ◽

Mohamed Yousuff Mohamed Imran ◽

Nooruddin Thajuddin ◽

D. Dhanasekaran

Keyword(s):

Gut Microbiome ◽

Human Gut ◽

Human Gut Microbiome ◽

Health And Disease

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Human genetic determinants of the gut microbiome and their associations with health and disease: a phenome-wide association study

Scientific Reports ◽

10.1038/s41598-020-70724-5 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Hilde E. Groot ◽

Yordi J. van de Vegte ◽

Niek Verweij ◽

Erik Lipsic ◽

Jacco C. Karper ◽

...

Keyword(s):

Gut Microbiome ◽

Healthy Aging ◽

Total Sample ◽

Causal Link ◽

Small Scale ◽

Nucleotide Polymorphisms ◽

Genetic Determinants ◽

Human Gut ◽

Human Gut Microbiome ◽

Health And Disease

Abstract Small-scale studies have suggested a link between the human gut microbiome and highly prevalent diseases. However, the extent to which the human gut microbiome can be considered a determinant of disease and healthy aging remains unknown. We aimed to determine the spectrum of diseases that are linked to the human gut microbiome through the utilization of its genetic determinants as a proxy for its composition. 180 single nucleotide polymorphisms (SNPs) known to influence the human gut microbiome were used to assess the association with health and disease outcomes in 422,417 UK Biobank participants. Potential causal estimates were obtained using a Mendelian randomization (MR) approach. From the total sample analysed (mean age was 57 ± 8 years), 194,567 (46%) subjects were male. Median exposure was 66-person years (interquartile range 59–72). Eleven SNPs were significantly associated with 28 outcomes (Bonferroni corrected P value < 4.63·10−6) including food intake, hypertension, atopy, COPD, BMI, and lipids. Multiple SNP MR pointed to a possible causal link between Ruminococcus flavefaciens and hypertension, and Clostridium and platelet count. Microbiota and their metabolites might be of importance in the interplay between overlapping pathophysiological processes, although challenges remain in establishing causal relationships.

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The human gut microbiome impacts health and disease

Comptes Rendus Biologies ◽

10.1016/j.crvi.2016.04.008 ◽

2016 ◽

Vol 339 (7-8) ◽

pp. 319-323 ◽

Cited By ~ 15

Author(s):

Stanislav Dusko Ehrlich

Keyword(s):

Gut Microbiome ◽

Human Gut ◽

Human Gut Microbiome ◽

Health And Disease

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Systematic characterization of human gut microbiome-secreted molecules by integrated multi-omics

ISME Communications ◽

10.1038/s43705-021-00078-0 ◽

2021 ◽

Vol 1 (1) ◽

Author(s):

Bianca De Saedeleer ◽

Antoine Malabirade ◽

Javier Ramiro-Garcia ◽

Janine Habier ◽

Jean-Pierre Trezzi ◽

...

Keyword(s):

Gut Microbiome ◽

Complex Mixture ◽

Host Cells ◽

Methodological Framework ◽

Secretion Systems ◽

Human Gut ◽

Healthy Human ◽

Human Gut Microbiome ◽

Health And Disease

AbstractThe human gut microbiome produces a complex mixture of biomolecules that interact with human physiology and play essential roles in health and disease. Crosstalk between micro-organisms and host cells is enabled by different direct contacts, but also by the export of molecules through secretion systems and extracellular vesicles. The resulting molecular network, comprised of various biomolecular moieties, has so far eluded systematic study. Here we present a methodological framework, optimized for the extraction of the microbiome-derived, extracellular biomolecular complement, including nucleic acids, (poly)peptides, and metabolites, from flash-frozen stool samples of healthy human individuals. Our method allows simultaneous isolation of individual biomolecular fractions from the same original stool sample, followed by specialized omic analyses. The resulting multi-omics data enable coherent data integration for the systematic characterization of this molecular complex. Our results demonstrate the distinctiveness of the different extracellular biomolecular fractions, both in terms of their taxonomic and functional composition. This highlights the challenge of inferring the extracellular biomolecular complement of the gut microbiome based on single-omic data. The developed methodological framework provides the foundation for systematically investigating mechanistic links between microbiome-secreted molecules, including those that are typically vesicle-associated, and their impact on host physiology in health and disease.

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Human genetic determinants of the gut microbiome and their associations with health and disease: a phenome-wide association study

European Heart Journal ◽

10.1093/ehjci/ehaa946.3642 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

H Groot ◽

Y.J Van De Vegte ◽

N Verweij ◽

E Lipsic ◽

J.C Karper ◽

...

Keyword(s):

Diabetes Mellitus ◽

Heart Failure ◽

Type 2 Diabetes ◽

Gut Microbiome ◽

Genetic Determinants ◽

Human Gut ◽

Human Gut Microbiome ◽

Disease Outcomes ◽

Health And Disease

Abstract Background Recent small-scale studies have suggested a link between the human gut microbiome and highly prevalent diseases. However, the extent to which the human gut microbiome can be considered a determinant of disease and healthy aging has not been well established. In this study, we aimed to determine the spectrum of diseases that are linked to the human gut microbiome through the utilization of its genetic determinants as a proxy for its composition. Methods Data from 422,417 unrelated individuals of Caucasian British ancestry with available genotype and matching genetic data from the UK biobank was analysed in this study. 35 single nucleotide polymorphisms (SNPs) known to influence the human gut microbiome were used to perform the phenome-wide association study. Our main outcome was the probability (risk) of health and disease outcomes associated with human genetic determinants of the microbiome. Results From the total sample analysed (mean age was 57±8 years), 194,567 (46%) subjects were male. Median exposure was 66-person years (interquartile range 59 to 72). Seven SNPs known to influence the human gut microbiome were significantly associated with 29 health and disease outcomes (false discovery rate <5%, P value <9.14×10–4) including food intake, health status parameters (inflammation, blood pressure and lipid levels), hypertension, type 2 diabetes mellitus, hypercholesterolemia, heart failure, renal failure, and osteoarthritis. Conclusions Human genetic determinants of the gut microbiome are associated with 29 specific health and disease outcomes including hypertension, type 2 diabetes mellitus, hypercholesterolemia, heart failure, renal failure, and osteoarthritis. Microbiota and their metabolites play an important role in the interplay between overlapping pathophysiological processes and could be considered as potential targets for the maintenance of health and reduction of disease risk. Heat map Funding Acknowledgement Type of funding source: None

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The Human Gut Phageome: Origins and Roles in the Human Gut Microbiome

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.643214 ◽

2021 ◽

Vol 11 ◽

Author(s):

Eleanor M. Townsend ◽

Lucy Kelly ◽

George Muscatt ◽

Joshua D. Box ◽

Nicole Hargraves ◽

...

Keyword(s):

Gut Microbiome ◽

Adult Life ◽

Microbial Populations ◽

Human Gut ◽

Bacterial Populations ◽

Human Gut Microbiome ◽

Microbiome Research ◽

Health And Disease ◽

Over Time

The investigation of the microbial populations of the human body, known as the microbiome, has led to a revolutionary field of science, and understanding of its impacts on human development and health. The majority of microbiome research to date has focussed on bacteria and other kingdoms of life, such as fungi. Trailing behind these is the interrogation of the gut viruses, specifically the phageome. Bacteriophages, viruses that infect bacterial hosts, are known to dictate the dynamics and diversity of bacterial populations in a number of ecosystems. However, the phageome of the human gut, while of apparent importance, remains an area of many unknowns. In this paper we discuss the role of bacteriophages within the human gut microbiome. We examine the methods used to study bacteriophage populations, how this evolved over time and what we now understand about the phageome. We review the phageome development in infancy, and factors that may influence phage populations in adult life. The role and action of the phageome is then discussed at both a biological-level, and in the broader context of human health and disease.

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GutCyc: a Multi-Study Collection of Human Gut Microbiome Metabolic Models

10.1101/055574 ◽

2016 ◽

Cited By ~ 1

Author(s):

Aria S. Hahn ◽

Tomer Altman ◽

Kishori M. Konwar ◽

Niels W. Hanson ◽

Dongjae Kim ◽

...

Keyword(s):

Gut Microbiome ◽

Large Scale ◽

High Throughput Sequencing ◽

Human Microbiome ◽

Therapeutic Interventions ◽

Human Gut ◽

Human Gut Microbiome ◽

Disease States ◽

Health And Disease ◽

Inflammatory Bowel

AbstractAdvances in high-throughput sequencing are reshaping how we perceive microbial communities inhabiting the human body, with implications for therapeutic interventions. Several large-scale datasets derived from hundreds of human microbiome samples sourced from multiple studies are now publicly available. However, idiosyncratic data processing methods between studies introduce systematic differences that confound comparative analyses. To overcome these challenges, we developed GUTCYC, a compendium of environmental pathway genome databases constructed from 418 assembled human microbiome datasets using METAPATHWAYS, enabling reproducible functional metagenomic annotation. We also generated metabolic network reconstructions for each metagenome using the PATHWAY TOOLS software, empowering researchers and clinicians interested in visualizing and interpreting metabolic pathways encoded by the human gut microbiome. For the first time, GUTCYC provides consistent annotations and metabolic pathway predictions, making possible comparative community analyses between health and disease states in inflammatory bowel disease, Crohn’s disease, and type 2 diabetes. GUTCYC data products are searchable online, or may be downloaded and explored locally using METAPATHWAYS and PATHWAY TOOLS.

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