Genetic determinants of gut microbiota composition and bile acid profiles in mice

Abstract

The microbial communities that inhabit the distal gut of humans and other mammals exhibit large inter-individual variation. While host genetics is a known factor that influences gut microbiota composition, the mechanisms underlying this variation remain largely unknown. Bile acids (BAs) are hormones that are produced by the host and chemically modified by gut bacteria. BAs serve as environmental cues and nutrients to microbes, but they can also have antibacterial effects. We hypothesized that host genetic variation in BA metabolism and homeostasis influence gut microbiota composition. To address this, we used the Diversity Outbred (DO) stock, a population of genetically distinct mice derived from eight founder strains. We characterized the fecal microbiota composition and plasma and cecal BA profiles from 400 DO mice maintained on a high-fat high-sucrose diet for ~22 weeks. Using quantitative trait locus (QTL) analysis, we identified several genomic regions associated with variations in both bacterial and BA profiles. Notably, we found overlapping QTL for Turicibacter sp . and plasma cholic acid, which mapped to a locus containing the gene for the ileal bile acid transporter, Slc10a2 . Mediation analysis and subsequent follow-up validation experiments suggest that differences in Slc10a2 gene expression associated with the different strains influences levels of both traits and revealed novel interactions between Turicibacter and BAs. This work illustrates how systems genetics can be utilized to generate testable hypotheses and provide insight into host-microbe interactions.

Eggshell and environmental bacteria contribute to the intestinal microbiota of growing chickens

“…Several of the core taxa identified in this study are currently being studied as important modulators of host physiology. Turicibacter (0.02-5.50% total reads/input group) is a highly heritable genus of bacteria that is able to interact with host-derived bile acids and play a role in the neurotransmitter regulation in the mammalian gut [50,51]. Romboutsia (1.15-19.34% total reads/input group) appeared as the second most highly abundant genera throughout the study, and was identified as a member of the core microbiota in both trials.…”

Self-reinoculation with fecal flora changes microbiota density and composition leading to an altered bile-acid profile in the mouse small intestine

“…Erysipelotrichales (including Turicibacter spp.) in the mouse ileum and cecum have been shown to be positively correlated with unconjugated ileal and cecal [62] and plasma [63] bile acids. Bacteroidales (including Muribaculum spp.)…”

Intestinal Barrier Breakdown and Mucosal Microbiota Disturbance in Neuromyelitis Optical Spectrum Disorders

“…Based on the data from the Metastats analysis on 40 bacteria at the genus level ( Table 2 ), among the 20 bacteria that were increased in NMOSD patients ( Table 2 , orders 1–20), including some short chain fatty acids-producing bacteria ( 19 – 22 ) ( Faecalibacterium , Roseburia , Coprococcus , Ruminococcaceae , Lachnospira ), which have protective role in colonic inflammation, and some proinflammatory bacteria, such as Granulicatella ( 23 ), Streptococcus ( 24 ), Proteus ( 25 ), and Desulfovibrio ( 26 ). Among the 20 bacteria that were decreased in NMOSD patients, most are conventional intestinal bacteria, and many are beneficial bacteria such as Rahnella ( 27 ), Lactococcus ( 28 ), Leptotrichia ( 29 ) and Turicibacter ( 30 ) ( Table 2 , orders 21–40). Granulicatella and Streptococcus , two well-studied bacteria, were significantly increased in NMOSD patients compared with HC subjects ( Figure 1E , p < 0.01 and Figure 1F , p < 0.05, respectively).…”