scholarly journals Deep characterization of the protein lysine acetylation in human gut microbiome and its alterations in patients with Crohn’s disease

2019 ◽  
Author(s):  
Xu Zhang ◽  
Zhibin Ning ◽  
Janice Mayne ◽  
Shelley A. Deeke ◽  
Krystal Walker ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiome ◽  
Human Microbiome ◽  
Host Protein ◽  
Lysine Acetylation ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Human Proteins ◽  
Protein Lysine Acetylation

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.

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

2016 ◽  
Vol 151 (4) ◽  
pp. 724-732 ◽  
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

scholarly journals Widespread protein lysine acetylation in gut microbiome and its alterations in patients with Crohn’s disease

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xu Zhang ◽  
Zhibin Ning ◽  
Janice Mayne ◽  
Yidai Yang ◽  
Shelley A. Deeke ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiome ◽  
Lysine Acetylation ◽  
Protein Lysine Acetylation

scholarly journals Revealing Protein-Level Functional Redundancy in the Human Gut Microbiome using Ultra-deep Metaproteomics

2021 ◽  
Author(s):  
Leyuan Li ◽  
Zhibin Ning ◽  
Xu Zhang ◽  
James Butcher ◽  
Caitlin Simopoulos ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Protein Level ◽  
Functional Organization ◽  
Human Microbiome ◽  
Functional Redundancy ◽  
Human Gut ◽  
Functional Roles ◽  
Human Gut Microbiome ◽  
Metagenomics Data ◽  
Network Approaches

Functional redundancy is a key property of ecosystems and represents the fact that phylogenetically unrelated taxa can play similar functional roles within an ecosystem. The redundancy of potential functions of human microbiome has been recently quantified using metagenomics data. Yet, the redundancy of functions which are actually expressed within the human microbiome remains largely unexplored. Here, we quantify the protein-level functional redundancy in the human gut microbiome using metaproteomics and network approaches. In particular, our ultra-deep metaproteomics approach revealed high protein-level functional redundancy and high nestedness in proteomic content networks - bipartite graphs that connect taxa with their expressed functions. We further examined multiple metaproteomics datasets and showed that various environmental factors, including individuality, biogeography, xenobiotics, and disease, significantly altered the protein-level functional redundancy. Finally, by projecting the bipartite proteomic content networks into unipartite weighted genus networks, functional hub genera across individual microbiomes were discovered, suggesting that there may be a universal principle of functional organization in microbiome assembly.

scholarly journals Captivity humanizes the primate microbiome

2016 ◽  
Vol 113 (37) ◽  
pp. 10376-10381 ◽  
Author(s):  
Jonathan B. Clayton ◽  
Pajau Vangay ◽  
Hu Huang ◽  
Tonya Ward ◽  
Benjamin M. Hillmann ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Meta Analysis ◽  
Human Microbiome ◽  
16S Rrna Gene Sequencing ◽  
Modern Human ◽  
Primate Species ◽  
Rrna Gene ◽  
Human Gut ◽  
Dietary Analysis ◽  
Human Gut Microbiome

The primate gastrointestinal tract is home to trillions of bacteria, whose composition is associated with numerous metabolic, autoimmune, and infectious human diseases. Although there is increasing evidence that modern and Westernized societies are associated with dramatic loss of natural human gut microbiome diversity, the causes and consequences of such loss are challenging to study. Here we use nonhuman primates (NHPs) as a model system for studying the effects of emigration and lifestyle disruption on the human gut microbiome. Using 16S rRNA gene sequencing in two model NHP species, we show that although different primate species have distinctive signature microbiota in the wild, in captivity they lose their native microbes and become colonized with Prevotella and Bacteroides, the dominant genera in the modern human gut microbiome. We confirm that captive individuals from eight other NHP species in a different zoo show the same pattern of convergence, and that semicaptive primates housed in a sanctuary represent an intermediate microbiome state between wild and captive. Using deep shotgun sequencing, chemical dietary analysis, and chloroplast relative abundance, we show that decreasing dietary fiber and plant content are associated with the captive primate microbiome. Finally, in a meta-analysis including published human data, we show that captivity has a parallel effect on the NHP gut microbiome to that of Westernization in humans. These results demonstrate that captivity and lifestyle disruption cause primates to lose native microbiota and converge along an axis toward the modern human microbiome.

scholarly journals Microbial ACBP/DBI-like genes are rare in the human gut microbiome and show no links with obesity

2021 ◽  
Author(s):  
Andrew Maltez Thomas ◽  
Francesco Asnicar ◽  
Guido Kroemer ◽  
Nicola Segata
Keyword(s):  
Gut Microbiome ◽  
Pathogenic Bacteria ◽  
Coenzyme A ◽  
Binding Protein ◽  
Human Microbiome ◽  
Human Metabolism ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Domains Of Life ◽  
Acyl Coenzyme A

Acyl coenzyme A (CoA) binding protein (ACBP), also called diazepam-binding inhibitor (DBI) is a phylogenetically conserved protein that is expressed by all eukaryotic species as well as by some bacteria. Since elevated ACBP/DBI levels play a major role in the inhibition of autophagy, increase in appetite and lipoanabolism that accompany obesity, we wondered whether ACBP/DBI produced by the human microbiome might affect host weight. We found that the genomes of bacterial commensals rarely contain ACBP/DBI homologues, which are rather encoded by genomes of some pathogenic or environmental taxa that were not prevalent in human feces. Exhaustive bioinformatic analyses of 1,899 gut samples from healthy individuals refuted the hypothesis that bacterial ACBP/DBI might affect the BMI in a physiological context. Thus, the physiological regulation of BMI is unlikely to be affected by microbial ACBP/DBI-like proteins. However, at the speculative level, it remains possible that ACBP/DBI produced by potential pathogenic bacteria might enhance their virulence by inhibiting autophagy and hence subverting innate immune responses. Importance Acyl coenzyme A (CoA) binding protein (ACBP) can be encoded by several organisms across the domains of life, including microbes, and has shown to play major roles in human metabolic processes. However, little is known about its presence in the human gut microbiome and whether its microbial counterpart could also play a role in human metabolism. In the present study, we found that microbial ACBP/DBI sequences were rarely present in the gut microbiome across multiple metagenomic datasets. Microbes that carried ACBP/DBI in the human gut microbiome included Saccharomyces cerevisiae, Lautropia mirabilis and Comamonas kerstersii, but these microorganisms were not associated with body-mass index, further indicating an unconvincing role for microbial ACBP/DBI in human metabolism.

scholarly journals Phage Diversity in the Human Gut Microbiome: a Taxonomist’s Perspective

mSystems ◽  
2021 ◽  
Author(s):  
Evelien M. Adriaenssens
Keyword(s):  
Gut Microbiome ◽  
Human Microbiome ◽  
Research Groups ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Global Oceans

Bacteriophages (phages) have been known for over a century, but only in the last 2 decades have we really come to appreciate how abundant and diverse they are. With that realization, research groups across the globe have shown the importance of phage-based processes in a myriad of environments, including the global oceans and soils, and as part of the human microbiome.

scholarly journals Phylogeny-corrected identification of microbial gene families relevant to human gut colonization

2017 ◽  
Author(s):  
Patrick H. Bradley ◽  
Stephen Nayfach ◽  
Katherine S. Pollard
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiome ◽  
Related Species ◽  
Gene Families ◽  
Gut Health ◽  
Human Gut ◽  
Bacterial Gene ◽  
Gut Colonization ◽  
Microbial Genes

AbstractThe mechanisms by which different microbes colonize the healthy human gut versus other body sites, the gut in disease states, or other environments remain largely unknown. Identifying microbial genes influencing fitness in the gut could lead to new ways to engineer probiotics or disrupt pathogenesis. We approach this problem by measuring the statistical association between having a species having a gene and the probability that the species is present in the gut microbiome. The challenge is that closely related species tend to be jointly present or absent in the microbiome and also share many genes, only a subset of which are involved in gut adaptation. We show that this phylogenetic correlation indeed leads to many false discoveries and propose phylogenetic linear regression as a powerful solution. To apply this method across the bacterial tree of life, where most species have not been experimentally phenotyped, we use metagenomes from hundreds of people to quantify each species’ prevalence in and specificity for the gut microbiome. This analysis reveals thousands of genes potentially involved in adaptation to the gut across species, including many novel candidates as well as processes known to contribute to fitness of gut bacteria, such as acid tolerance in Bacteroidetes and sporulation in Firmicutes. We also find microbial genes associated with a preference for the gut over other body sites, which are significantly enriched for genes linked to fitness in an in vivo competition experiment. Finally, we identify gene families associated with higher prevalence in patients with Crohn’s disease, including Proteobacterial genes involved in conjugation and fimbria regulation, processes previously linked to inflammation. These gene targets may represent new avenues for modulating host colonization and disease. Our strategy of combining metagenomics with phylogenetic modeling is general and can be used to identify genes associated with adaptation to any environment.Author SummaryWhy do certain microbes and not others colonize our gut, and why do they differ between healthy and sick people? One explanation is the genes in their genomes. If we can find microbial genes involved in gut adaptation, we may be able to keep out pathogens and encourage the growth of beneficial microbes. One could look for genes that were present more often in prevalent microbes, and less often in rare ones.However, this ignores that related species are more likely to share an environment and also share many unrelated phenotypes simply because of common ancestry. To solve this problem, we used a method from ecology that accounts for phylogenetic relatedness. We first calculated gut prevalence for thousands of species using a compendium of shotgun sequencing data, then tested for genes associated with prevalence, adjusting for phylogenetic relationships. We found genes that are associated with overall gut prevalence, with a preference for the gut over other body sites, and with the gut in Crohn’s disease versus health. Many of these findings have biological plausibility based on existing literature. We also showed agreement with the results of a previously published high-throughput screen of bacterial gene knockouts in mice. These results, and this type of analysis, may eventually lead to new strategies for maintaining gut health.

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

2016 ◽  
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.

scholarly journals On the Stability Landscape of the Human Gut Microbiome: Implications for Microbiome-based Therapies

2017 ◽  
Author(s):  
Travis E. Gibson ◽  
Vincent Carey ◽  
Amir Bashan ◽  
Elizabeth L. Hohmann ◽  
Scott T. Weiss ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Human Microbiome ◽  
Fecal Microbiota ◽  
New Method ◽  
Human Gut ◽  
Cross Sectional ◽  
Human Gut Microbiome ◽  
Microbiome Research ◽  
The Stability

AbstractUnderstanding how gut microbial species determine their abundances is crucial in developing any microbiome-based therapy. Towards that end, we show that the compositions of our gut microbiota have characteristic and attractive steady states, and hence respond to perturbations in predictable ways. This is achieved by developing a new method to analyze the stability landscape of the human gut microbiome. In order to illustrate the efficacy of our method and its ecological interpretation in terms of asymptotic stability, this novel method is applied to various human cohorts, including large cross-sectional studies, long longitudinal studies with frequent sampling, and perturbation studies via fecal microbiota transplantation, antibiotic and probiotic treatments. These findings will facilitate future ecological modeling efforts in human microbiome research. Moreover, the method allows for the prediction of the compositional shift of the gut microbiome during the fecal microbiota transplantation process. This result holds promise for translational applications, such as, personalized donor selection when performing fecal microbiota transplantations.One Sentence SummaryA new method for analyzing the stability landscape of the human gut microbiome and predicting its steady-state composition is developed.

scholarly journals Convergence of human and Old World monkey gut microbiomes demonstrates the importance of human ecology over phylogeny

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Katherine R. Amato ◽  
Elizabeth K. Mallott ◽  
Daniel McDonald ◽  
Nathaniel J. Dominy ◽  
Tony Goldberg ◽  
...  
Keyword(s):  
Individual Variation ◽  
Gut Microbiome ◽  
World Monkey ◽  
Human Microbiome ◽  
Human Gut ◽  
Old World ◽  
Microbiome Composition ◽  
Human Gut Microbiome ◽  
Functional Potential ◽  
Physiological Adaptations

Abstract Background Comparative data from non-human primates provide insight into the processes that shaped the evolution of the human gut microbiome and highlight microbiome traits that differentiate humans from other primates. Here, in an effort to improve our understanding of the human microbiome, we compare gut microbiome composition and functional potential in 14 populations of humans from ten nations and 18 species of wild, non-human primates. Results Contrary to expectations from host phylogenetics, we find that human gut microbiome composition and functional potential are more similar to those of cercopithecines, a subfamily of Old World monkey, particularly baboons, than to those of African apes. Additionally, our data reveal more inter-individual variation in gut microbiome functional potential within the human species than across other primate species, suggesting that the human gut microbiome may exhibit more plasticity in response to environmental variation compared to that of other primates. Conclusions Given similarities of ancestral human habitats and dietary strategies to those of baboons, these findings suggest that convergent ecologies shaped the gut microbiomes of both humans and cercopithecines, perhaps through environmental exposure to microbes, diet, and/or associated physiological adaptations. Increased inter-individual variation in the human microbiome may be associated with human dietary diversity or the ability of humans to inhabit novel environments. Overall, these findings show that diet, ecology, and physiological adaptations are more important than host-microbe co-diversification in shaping the human microbiome, providing a key foundation for comparative analyses of the role of the microbiome in human biology and health.

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