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

AbstractMetagenomic and metaproteomic approaches have been used to study the composition and functions of the microbiota. However, no studies have examined post-translational modifications (PTM) on human microbiome proteins at the metaproteome level, and it remains unknown whether the microbial PTM is altered or not in patient microbiome. Herein we used anti-acetyl-lysine (Kac) antibody enrichment strategy and mass spectrometry to characterize the protein lysine acetylation in human microbiome, which successfully identified 35,200 Kac peptides corresponding to 31,821 Kac sites from the microbial or host proteins in human gut microbiome samples. The gut microbial proteins exhibited Kac motifs that were distinct from those of human proteins. Functional analysis showed that microbial Kac proteins were significantly enriched in energy production and abundant in enzymes related to transferases and oxidoreductases. Applying to the analysis of pediatric Crohn’s disease (CD) patient microbiome identified 52 host and 136 microbial protein Kac sites that were differentially abundant in CD versus controls. Interestingly, most of the decreased Kac sites in CD were derived from Firmicutes and most of the increased sites were derived from Bacteroidetes. Forty-six out of the 52 differentially abundant human protein Kac sites were increased in CD patients, including those on calprotectin, lactotransferrin and immunoglobulins. Taken together, this study provides an efficient approach to study the lysine acetylation in microbiome and revealed taxon-specific alterations in the lysine acetylome as well as changes in host protein acetylation levels in intestinal samples during the on-set of disease in CD patients.

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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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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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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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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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Human gut microbiome composition and tryptophan metabolites were changed differently by fast food and Mediterranean diet in 4 days: a pilot study

Nutrition Research ◽

10.1016/j.nutres.2020.03.005 ◽

2020 ◽

Vol 77 ◽

pp. 62-72 ◽

Cited By ~ 3

Author(s):

Chenghao Zhu ◽

Lisa Sawrey-Kubicek ◽

Elizabeth Beals ◽

Chris H. Rhodes ◽

Hannah Eve Houts ◽

...

Keyword(s):

Pilot Study ◽

Mediterranean Diet ◽

Gut Microbiome ◽

Fast Food ◽

Human Gut ◽

Microbiome Composition ◽

Human Gut Microbiome ◽

Tryptophan Metabolites

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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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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.

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