Christensenella strain resources, genomic/metabolomic profiling, and association with host at species level

Abstract

The gut commensal bacteria <i>Christensenellaceae</i> species are negatively associated with many metabolic diseases, and have been seen as promising next-generation probiotics. However, the cultured <i>Christensenellaceae</i> strain resources were limited, and their beneficial mechanisms for improving metabolic diseases have yet to be explored. In this study, we developed a method that enabled the enrichment and cultivation of <i>Christensenellaceae</i> strains from fecal samples. Using this method, a collection of <i>Christensenellaceae</i> Gut Microbial Biobank (ChrisGMB) was established, composed of 87 strains and genomes that represent 14 species of 8 genera. Seven species were first described and the cultured <i>Christensenellaceae</i> resources have been significantly expanded at species and strain levels. <i>Christensenella</i> strains exerted different abilities in utilization of various complex polysaccharides and other carbon sources, exhibited host-adaptation capabilities such as acid tolerance and bile tolerance, produced a wide range of volatile probiotic metabolites and secondary bile acids. Cohort analyses demonstrated that <i>Christensenellaceae</i> and <i>Christensenella</i> were prevalent in various cohorts and the abundances were significantly reduced in T2D and OB cohorts. At species level, <i>Christensenellaceae</i> showed different changes among healthy and disease cohorts. <i>C. faecalis</i>, <i>F. tenuis</i>, <i>L. tenuis</i>, and <i>Guo. tenuis</i> significantly reduced in all the metabolic disease cohorts. The relative abundances of <i>C. minuta, C. hongkongensis</i> and <i>C. massiliensis</i> showed no significant change in NAFLD and ACVD. and <i>C. tenuis</i> and <i>C. acetigenes</i> showed no significant change in ACVD, and <i>Q. tenuis</i> and <i>Geh. tenuis</i> showed no significant change in NAFLD, when compared with the HC cohort. So far as we know, this is the largest collection of cultured resource and first exploration of <i>Christensenellaceae</i> prevalences and abundances at species level.