Comparative genomics reveals extensive intra-species genetic divergence of the prevalent gut commensal Ruminococcus gnavus

Ruminococcus gnavus is prevalent in the intestines of humans and animals, and ambiguities have been reported regarding its relations with the development of diseases and host well-being. We postulate the ambiguities of its function in different cases may be attributed to strain-level variability of genomic features of R. gnavus. We performed comparative genomic and pathogenicity prediction analysis on 152 filtered high-quality genomes, including 4 genomes of strains isolated from healthy adults in this study. The mean G+C content of genomes of R. gnavus was 42.73 +/- 0.33 mol%, and the mean genome size was 3.46 +/- 0.34 Mbp. Genome-wide evolutionary analysis revealed R. gnavus genomes were divided into three major phylogenetic clusters. Pan-core genome analysis revealed that there was a total of 28 072 predicted genes, and the core genes, soft-core genes, shell genes and cloud genes accounted for 3.74% (1051/28 072), 1.75% (491/28 072), 9.88 % (2774/28 072) and 84.63% (23 756/28 072) of the total genes, respectively. The small proportion of core genes reflected the wide divergence among R. gnavus strains. We found certain coding sequences with determined health benefits (such as vitamin production and arsenic detoxification), whilst some had an implication of health adversity (such as sulfide dehydrogenase subunits). The functions of the majority of core genes were unknown. The most widespread genes functioning in antibiotic resistance and virulence are tetO (tetracycline-resistance gene, present in 75 strains) and cps4J (capsular polysaccharide biosynthesis protein Cps4J encoding gene, detected in 3 genomes), respectively. Our results revealed genomic divergence and the existence of certain safety-relevant factors of R. gnavus. This study provides new insights for understanding the genomic features and health relevance of R. gnavus, and raises concerns regarding predicted prevalent pathogenicity and antibiotic resistance among most of the strains.