Abstract
The gut microbiota is essentially a multifunctional bioreactor within a human being. The exploration of its enormous metabolic potential provides insights into the mechanisms underlying microbial ecology and interactions with the host. The data obtained using “shotgun” metagenomics capture information about the whole spectrum of microbial functions. However, each new study presenting new sequencing data tends to extract only a little of the information concerning the metabolic potential and often omits specific functions. A meta-analysis of the available data with an emphasis on biomedically relevant gene groups can unveil new global trends in the gut microbiota. As a step toward the reuse of metagenomic data, we developed a method for the quantitative profiling of user-defined groups of genes in human gut metagenomes. This method is based on the quick analysis of a gene coverage matrix obtained by pre-mapping the metagenomic reads to a global gut microbial catalogue. The method was applied to profile the abundance of several gene groups related to antibiotic resistance, phages, biosynthesis clusters and carbohydrate degradation in 784 metagenomes from healthy populations worldwide and patients with inflammatory bowel diseases and obesity. We discovered country-wise functional specifics in gut resistome and virome compositions. The most distinct features of the disease microbiota were found for Crohn’s disease, followed by ulcerative colitis and obesity. Profiling of the genes belonging to crAssphage showed that its abundance varied across the world populations and was not associated with clinical status. We demonstrated temporal resilience of crAssphage and the influence of the sample preparation protocol on its detected abundance. Our approach offers a convenient method to add value to accumulated “shotgun” metagenomic data by helping researchers state and assess novel biological hypotheses.
Highlights
The human gut microbiota forms a complex ecosystem consisting of hundreds of bacterial species [1]
We demonstrate the applicability of our method by estimating the relative abundance of several groups of clinically relevant genes, including antibiotic resistance, carbohydrate degradation, biosynthesis, and phage taxonomic markers, in metagenomic datasets from recently published international large-scale studies
The approach consists of finding genes similar to the targeted group in a global gut microbial gene catalogue and extracting the abundance values for the detected matching genes basing on a precomputed mapping of metagenomic datasets on the global catalogue
Summary
The human gut microbiota forms a complex ecosystem consisting of hundreds of bacterial species [1]. It is a metabolically active “organ”, with its total metabolic potential covering most reactions known to occur in living organisms. As the gut community has lived in tight longterm coexistence with the host, many of the identified functions confer various benefits to humans. Gut bacteria are able to ferment indigestible dietary polysaccharides to produce short-chain fatty acids [3], metabolize xenobiotics [4] and human-produced metabolites (i.e., bile acids [5]), synthesize vitamins and other beneficial substances [6] [7] and provide protection from pathogens [8]. Functional analysis of the microbiota encompasses a family of approaches for the qualitative and quantitative profiling of specific gene sets involved in each of these functions
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