Genomic variation landscape of the human gut microbiome

Abstract

While large-scale efforts have rapidly advanced the understanding and practical impact of human genomic variation, the latter is largely unexplored in the human microbiome. We therefore developed a framework for metagenomic variation analysis and applied it to 252 fecal metagenomes of 207 individuals from Europe and North America. Using 7.4 billion reads aligned to 101 reference species, we detected 10.3 million single nucleotide polymorphisms (SNPs), 107,991 short indels, and 1,051 structural variants. The average ratio of non-synonymous to synonymous polymorphism rates of 0.11 was more variable between gut microbial species than across human hosts. Subjects sampled at varying time intervals exhibited individuality and temporal stability of SNP variation patterns, despite considerable composition changes of their gut microbiota. This implies that individual-specific strains are not easily replaced and that an individual might have a unique metagenomic genotype, which may be exploitable for personalized diet or drug intake.

Integrated multi-omics of the human gut microbiome in a case study of familial type 1 diabetes

“…In addition to community stability, the persistence of individualspecific strains has been documented 4,5 . To explore whether strain specificity also translates to the functional level, we analysed the encoded functional potential and corresponding expression profiles of closely related reconstructed genomes recovered from different samples.…”

“…etagenomic studies of faecal samples have provided deep insights into the structure and functional potential of microbial communities within the human gastrointestinal tract 1,2 , revealing their inter-individual variability 3 and apparent intra-individual stability 4,5 . Case-control studies have associated microbial traits in individuals with patterns of diseases, thereby implicating gastrointestinal microbial communities in a range of human disorders [6][7][8][9][10] .…”

Subspecies in the global human gut microbiome

“…To be able to determine population structure without relying on limited or biased sets of pan‐genomes (Gordienko et al , 2013), we explored the natural genomic variation of the human gut microbiome (Schloissnig et al , 2013; Luo et al , 2015; Nayfach et al , 2016; Lloyd‐Price et al , 2017; Truong et al , 2017). To this end, we assessed the microbial genetic landscape of 2,144 deeply sequenced human stool metagenomes from nine countries, spanning three continents, including published (Huttenhower et al , 2012; Qin et al , 2012; Karlsson et al , 2013; Le Chatelier et al , 2013; Zeller et al , 2014) as well as 298 newly generated ones (Table EV1).…”

“…It has been previously shown that overall strain‐level composition is generally stable (Schloissnig et al , 2013; Lloyd‐Price et al , 2017; Truong et al , 2017), while upon perturbations, such as fecal microbiota transplantation, lasting changes in strain populations can occur (Li et al , 2016). …”

“…These provide a meaningful grouping of microbial strains, which correspond to a more fine‐grained level of variation that has been the focus of previous studies (Schloissnig et al , 2013; Nayfach et al , 2016; Lloyd‐Price et al , 2017; Truong et al , 2017). In contrast to gut microbial strains, the vast majority (> 95%) of which is specific to an individual host (Truong et al , 2017), most subspecies can be detected ubiquitously in the global human population and only few appear to be geographically restricted.…”