Extensive Strain-Level Copy-Number Variation across Human Gut Microbiome Species

Abstract

SUMMARY Within each bacterial species, different strains may vary in the set of genes they encode or in the copy number of these genes. Yet, taxonomic characterization of the human microbiota is often limited to the species level or to previously sequenced strains, and accordingly, the prevalence of intra-species variation, its functional role, and its relation to host health remain unclear. Here we present a first comprehensive large-scale analysis of intra-species copy number variation in the gut microbiome, introducing a rigorous computational pipeline for detecting such variation directly from shotgun metagenomic data. We uncover a large set of variable genes in numerous species and demonstrate that this variation has significant functional and clinically-relevant implications. We additionally infer intra-species compositional profiles, identifying population structure shifts and the presence of yet uncharacterized variants. Our results highlight the complex relationship between microbiome composition and functional capacity, linking metagenome-level compositional shifts to strain-level variation.

The Mouse Intestinal Bacterial Collection (miBC) provides host-specific insight into cultured diversity and functional potential of the gut microbiota

“…Moreover, key metabolic functions such as the conversion of bile acids require more detailed investigation. Also, strain diversity is most probably very important in gut environments 41 , but the collection offers resolution at the strain level for only a few species (especially lactobacilli), as the aim was to cover as much diversity as possible at the species level. Nevertheless, recent metagenomic work 41 also emphasizes the necessity to obtain reference genomes and thus the benefit of isolating and describing bacteria, as done extensively in the present work.…”

“…Also, strain diversity is most probably very important in gut environments 41 , but the collection offers resolution at the strain level for only a few species (especially lactobacilli), as the aim was to cover as much diversity as possible at the species level. Nevertheless, recent metagenomic work 41 also emphasizes the necessity to obtain reference genomes and thus the benefit of isolating and describing bacteria, as done extensively in the present work. Hence, knowledge of the mouse gut bacterial diversity made available via miBC can be viewed as a foundation that now requires effort by the entire community of gut microbiome researchers for further development.…”

Intraspecific Competition Impacts Vibrio fischeri Strain Diversity during Initial Colonization of the Squid Light Organ

“…Genetically different Gilliamella isolates displayed different levels of pectin degradation, suggesting unique niche adaptation for each strain within the honey bee gut. Within the human gut microbiome, significant intraspecies copy number variation was detected among genes that function in transport, sugar metabolism, and antibiotic resistance (39), supporting the notion that strain diversity can provide novel functions within the community. Interestingly, the population structures for many of the species were unique in each sample, indicating the individualized nature of the human gut microbiota.…”

Human symbionts inject and neutralize antibacterial toxins to persist in the gut

“…gut microbiome | microbial ecology | type VI secretion | symbiosis I nterpersonal variation in gut microbial community composition, even at the species or strain level, can determine the contribution of these communities to cancer risk, drug metabolism, caloric extraction from diet, infectious disease resistance, and other responses (1)(2)(3)(4)(5). However, the rules that determine community membership, especially at the species or strain level, are largely undefined.…”