scholarly journals Interplay between the human gut microbiome and host metabolism

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Alessia Visconti ◽  
Caroline I. Le Roy ◽  
Fabio Rosa ◽  
Niccolò Rossi ◽  
Tiphaine C. Martin ◽  
...  
Keyword(s):  
Human Health ◽  
Gut Microbiome ◽  
Metabolic Pathways ◽  
Blood Metabolites ◽  
Sequencing Data ◽  
Human Gut ◽  
Metabolic Potential ◽  
Microbial Ecosystem ◽  
Microbial Metabolic Potential ◽  
Host Metabolism

Abstract The human gut is inhabited by a complex and metabolically active microbial ecosystem. While many studies focused on the effect of individual microbial taxa on human health, their overall metabolic potential has been under-explored. Using whole-metagenome shotgun sequencing data in 1,004 twins, we first observed that unrelated subjects share, on average, almost double the number of metabolic pathways (82%) than species (43%). Then, using 673 blood and 713 faecal metabolites, we found metabolic pathways to be associated with 34% of blood and 95% of faecal metabolites, with over 18,000 significant associations, while species showed less than 3,000 associations. Finally, we estimated that the microbiome was involved in a dialogue between 71% of faecal, and 15% of blood, metabolites. This study underlines the importance of studying the microbial metabolic potential rather than focusing purely on taxonomy to find therapeutic and diagnostic targets, and provides a unique resource describing the interplay between the microbiome and the systemic and faecal metabolic environments.

scholarly journals Interplay between the human gut microbiome and host metabolism

2019 ◽  
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.

scholarly journals Identifying determinants of bacterial fitness in a model of human gut microbial succession

2020 ◽  
Vol 117 (5) ◽  
pp. 2622-2633 ◽  
Author(s):  
Lihui Feng ◽  
Arjun S. Raman ◽  
Matthew C. Hibberd ◽  
Jiye Cheng ◽  
Nicholas W. Griffin ◽  
...  
Keyword(s):  
Community Assembly ◽  
Metabolic Pathways ◽  
Feature Reduction ◽  
Human Infant ◽  
Human Gut ◽  
Metabolic Potential ◽  
Transcriptional Responses ◽  
Carbohydrate Utilization ◽  
Fecal Samples ◽  
Phase Strains

Human gut microbiota development has been associated with healthy growth but understanding the determinants of community assembly and composition is a formidable challenge. We cultured bacteria from serially collected fecal samples from a healthy infant; 34 sequenced strains containing 103,102 genes were divided into two consortia representing earlier and later stages in community assembly during the first six postnatal months. The two consortia were introduced alone (singly), or sequentially in different order, or simultaneously into young germ-free mice fed human infant formula. The pattern of fitness of bacterial strains observed across the different colonization conditions indicated that later-phase strains substantially outcompete earlier-phase strains, although four early-phase members persist. Persistence was not determined by order of introduction, suggesting that priority effects are not prominent in this model. To characterize succession in the context of the metabolic potential of consortium members, we performed in silico reconstructions of metabolic pathways involved in carbohydrate utilization and amino acid and B-vitamin biosynthesis, then quantified the fitness (abundance) of strains in serially collected fecal samples and their transcriptional responses to different histories of colonization. Applying feature-reduction methods disclosed a set of metabolic pathways whose presence and/or expression correlates with strain fitness and that enable early-stage colonizers to survive during introduction of later colonizers. The approach described can be used to test the magnitude of the contribution of identified metabolic pathways to fitness in different community contexts, study various ecological processes thought to govern community assembly, and facilitate development of microbiota-directed therapeutics.

scholarly journals Dietary Components, Microbial Metabolites and Human Health: Reading between the Lines

Foods ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1045
Author(s):  
Yao Guo ◽  
Xiaohan Bian ◽  
Jiali Liu ◽  
Ming Zhu ◽  
Lin Li ◽  
...  
Keyword(s):  
Linoleic Acid ◽  
Gut Microbiota ◽  
Human Health ◽  
Kynurenic Acid ◽  
Molecular Mechanisms ◽  
Eating Habits ◽  
Short Chain Fatty Acids ◽  
Human Gut ◽  
Dietary Components ◽  
Host Metabolism

Trillions of bacteria reside in the human gut and they metabolize dietary substances to obtain nutrients and energy while producing metabolites. Therefore, different dietary components could affect human health in various ways through microbial metabolism. Many such metabolites have been shown to affect human physiological activities, including short-chain fatty acids metabolized from carbohydrates; indole, kynurenic acid and para-cresol, metabolized from amino acids; conjugated linoleic acid and linoleic acid, metabolized from lipids. Here, we review the features of these metabolites and summarize the possible molecular mechanisms of their metabolisms by gut microbiota. We discuss the potential roles of these metabolites in health and diseases, and the interactions between host metabolism and the gut microbiota. We also show some of the major dietary patterns around the world and hope this review can provide insights into our eating habits and improve consumers’ health conditions.

scholarly journals Pet-Human Gut Microbiome Host Classifier Using Data from Different Studies

2020 ◽  
Vol 8 (10) ◽  
pp. 1591
Author(s):  
Nadia Bykova ◽  
Nikita Litovka ◽  
Anna Popenko ◽  
Sergey Musienko
Keyword(s):  
Gut Microbiome ◽  
Environmental Data ◽  
Domestic Cat ◽  
Sequencing Data ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Feature Importance ◽  
Importance Analysis ◽  
Using Data ◽  
Sources Of Contamination

(1) Background: microbiome host classification can be used to identify sources of contamination in environmental data. However, there is no ready-to-use host classifier. Here, we aimed to build a model that would be able to discriminate between pet and human microbiomes samples. The challenge of the study was to build a classifier using data solely from publicly available studies that normally contain sequencing data for only one type of host. (2) Results: we have developed a random forest model that distinguishes human microbiota from domestic pet microbiota (cats and dogs) with 97% accuracy. In order to prevent overfitting, samples from several (at least four) different projects were necessary. Feature importance analysis revealed that the model relied on several taxa known to be key components in domestic cat and dog microbiomes (such as Fusobacteriaceae and Peptostreptococcaeae), as well as on some taxa exclusively found in humans (as Akkermansiaceae). (3) Conclusion: we have shown that it is possible to make a reliable pet/human gut microbiome classifier on the basis of the data collected from different studies.

scholarly journals Inter-determination of blood metabolite levels and gut microbiome supported by Mendelian randomization

2020 ◽  
Author(s):  
Xiaomin Liu ◽  
Xin Tong ◽  
Yuanqiang Zou ◽  
Xiaoqian Lin ◽  
Hui Zhao ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Genetic Information ◽  
Mendelian Randomization ◽  
The Other ◽  
Whole Body ◽  
Blood Metabolites ◽  
Whole Genome ◽  
Sequencing Data ◽  
Pectin Degradation

AbstractThe gut microbiome has been implicated in a variety of physiological states. Controversy over causality, however, has always haunted microbiome studies. Here, we utilized the bidirectional Mendelian randomization (MR) approach to address questions that are not yet mature for more costly randomized interventions. From a total of 3,432 Chinese individuals with shotgun sequencing data for whole genome and whole metagenome, as well as anthropometric and blood metabolic traits, we identified 58 causal relationships between the gut microbiome and blood metabolites, and replicated 43 out of the 58. Gut microbiome could determine features in the blood. For example, increased fecal relative abundances of Oscillibacter and Alistipes were causally linked to decreased triglyceride concentration, and fecal microbial module pectin degradation might increase serum uric acid. On the other hand, blood features may determine gut microbial features, e.g. glutamic acid appeared to decrease Oxalobacter, and a few members of Proteobacteria were unidirectionally influenced by cardiometabolically important metabolites such as 5-methyltetrahydrofolic acid, alanine, as well as selenium. This study illustrates the value of human genetic information to help prioritize gut microbial features for mechanistic and clinical studies. The results are consistent with whole-body cross-talks of the microbiome and the circulating molecules.

scholarly journals Polyphenol utilization proteins in human gut microbiome

2021 ◽  
Author(s):  
Bo Zheng ◽  
Yinchao He ◽  
Pengxiang Zhang ◽  
Yi-Xin Huo ◽  
Yanbin Yin
Keyword(s):  
Human Health ◽  
Gut Microbiome ◽  
Sequence Similarity ◽  
Gene Clusters ◽  
Metagenomic Data ◽  
Human Populations ◽  
Human Gut ◽  
Systematic Classification ◽  
Dietary Polyphenols ◽  
Human Gut Microbiome

Dietary polyphenols can significantly benefit human health, but their bioavailability is metabolically controlled by human gut microbiota. To facilitate the study of polyphenol metabolism for human gut health, we have manually curated experimentally characterized polyphenol utilization proteins (PUPs) from published literature. This resulted in 60 experimentally characterized PUPs (named seeds) with various metadata, such as species and substrate. Further database search found 107,851 homologs of the seeds from UniProt and UHGP (Unified Human Gastrointestinal Protein) databases. All PUP seeds and homologs were classified into protein classes, families and subfamilies based on Enzyme Commission (EC) numbers, Pfam (protein family) domains and sequence similarity networks. By locating PUP homologs in the genomes of UHGP, we have identified 1,074 physically linked PUP gene clusters (PGCs), which are potentially involved in polyphenol metabolism in the human gut. The gut microbiome of Africans was consistently ranked the top in terms of the abundance and prevalence of PUP homologs and PGCs among all geographical continents. This reflects the fact that dietary polyphenols are more commonly consumed by African population than other populations such as Europeans and North Americans. A case study of the Hadza hunter-gatherer microbiome verified the feasibility of using dbPUP to profile metagenomic data for biologically meaningful discovery, suggesting an association between diet and PUP abundance. A Pfam domain enrichment analysis of PGCs identified a number of putatively novel PUP families. Lastly, a user-friendly web interface ( https://bcb.unl.edu/dbpup/ ) provides all the data online to facilitate the research of polyphenol metabolism for improved human health. Importance Long-term consumption of polyphenol-rich foods have been shown to lower the risk of various human diseases such as cardiovascular diseases, cancers, and metabolic diseases. Raw polyphenols are often enzymatically processed by gut microbiome, which encode various polyphenol utilization proteins (PUPs) to produce metabolites with much higher bioaccessibility to gastrointestinal cells. This study delivered dbPUP as an online database for experimentally characterized PUPs and their homologs in human gut microbiome. This work also performed a systematic classification of PUPs into enzyme classes, families, and subfamilies. The signature Pfam domains were identified for PUP families, enabling conserved domain-based PUP annotation. This standardized sequence similarity-based PUP classification system offered a guideline for the future inclusion of new experimentally characterized PUPs and the creation of new PUP families. An in-depth data analysis was further conducted on PUP homologs and physically linked PUP gene clusters (PGCs) in gut microbiomes of different human populations.

scholarly journals Gut Microbiome Toxicity: Connecting the Environment and Gut Microbiome-Associated Diseases

Toxics ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 19 ◽  
Author(s):  
Pengcheng Tu ◽  
Liang Chi ◽  
Wanda Bodnar ◽  
Zhenfa Zhang ◽  
Bei Gao ◽  
...  
Keyword(s):  
Human Health ◽  
Gut Microbiome ◽  
Human Disease ◽  
Disease Risk ◽  
Environmental Chemicals ◽  
Toxic Effects ◽  
Toxicity Evaluation ◽  
Human Gut ◽  
Associated Diseases ◽  
Environmental Agents

The human gut microbiome can be easily disturbed upon exposure to a range of toxic environmental agents. Environmentally induced perturbation in the gut microbiome is strongly associated with human disease risk. Functional gut microbiome alterations that may adversely influence human health is an increasingly appreciated mechanism by which environmental chemicals exert their toxic effects. In this review, we define the functional damage driven by environmental exposure in the gut microbiome as gut microbiome toxicity. The establishment of gut microbiome toxicity links the toxic effects of various environmental agents and microbiota-associated diseases, calling for more comprehensive toxicity evaluation with extended consideration of gut microbiome toxicity.

scholarly journals An extended reconstruction of human gut microbiota metabolism of dietary compounds

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Telmo Blasco ◽  
Sergio Pérez-Burillo ◽  
Francesco Balzerani ◽  
Daniel Hinojosa-Nogueira ◽  
Alberto Lerma-Aguilera ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Human Health ◽  
Metabolic Networks ◽  
16S Rrna Gene Sequencing ◽  
Complex Problem ◽  
Rrna Gene ◽  
Limited Information ◽  
Sequencing Data ◽  
Human Gut ◽  
Human Gut Microbiota

AbstractUnderstanding how diet and gut microbiota interact in the context of human health is a key question in personalized nutrition. Genome-scale metabolic networks and constraint-based modeling approaches are promising to systematically address this complex problem. However, when applied to nutritional questions, a major issue in existing reconstructions is the limited information about compounds in the diet that are metabolized by the gut microbiota. Here, we present AGREDA, an extended reconstruction of diet metabolism in the human gut microbiota. AGREDA adds the degradation pathways of 209 compounds present in the human diet, mainly phenolic compounds, a family of metabolites highly relevant for human health and nutrition. We show that AGREDA outperforms existing reconstructions in predicting diet-specific output metabolites from the gut microbiota. Using 16S rRNA gene sequencing data of faecal samples from Spanish children representing different clinical conditions, we illustrate the potential of AGREDA to establish relevant metabolic interactions between diet and gut microbiota.

scholarly journals Analysis of Human Gut Microbiome: Taxonomy and Metabolic Functions in Thai Adults

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 331
Author(s):  
Nachon Raethong ◽  
Massalin Nakphaichit ◽  
Narissara Suratannon ◽  
Witida Sathitkowitchai ◽  
Wanlapa Weerapakorn ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Asian Country ◽  
Rrna Gene ◽  
Metagenomic Sequencing ◽  
Sequencing Data ◽  
Human Gut ◽  
Thai Population ◽  
Shotgun Metagenomics ◽  
Human Gut Microbiome ◽  
Metabolic Functions

The gut microbiome plays a major role in the maintenance of human health. Characterizing the taxonomy and metabolic functions of the human gut microbiome is necessary for enhancing health. Here, we analyzed the metagenomic sequencing, assembly and construction of a meta-gene catalogue of the human gut microbiome with the overall aim of investigating the taxonomy and metabolic functions of the gut microbiome in Thai adults. As a result, the integrative analysis of 16S rRNA gene and whole metagenome shotgun (WMGS) sequencing data revealed that the dominant gut bacterial families were Lachnospiraceae and Ruminococcaceae of the Firmicutes phylum. Consistently, across 3.8 million (M) genes annotated from 163.5 gigabases (Gb) of WMGS sequencing data, a significant number of genes associated with carbohydrate metabolism of the dominant bacterial families were identified. Further identification of bacterial community-wide metabolic functions promisingly highlighted the importance of Roseburia and Faecalibacterium involvement in central carbon metabolism, sugar utilization and metabolism towards butyrate biosynthesis. This work presents an initial study of shotgun metagenomics in a Thai population-based cohort in a developing Southeast Asian country.

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