The secondary bile acid isoursodeoxycholate correlates with post-prandial lipemia, inflammation, and appetite and changes post-bariatric surgery

The Gut Microbiome Strongly Mediates the impact of Lifestyle combined variables on Cardiometabolic Phenotypes

“…Among these, high-impact mediations explaining more than 20% of the QASD score's effect on serum metabolome involved 27 MGS and 21 metabolites. MGS include some the above cited MGS like the increase in C. bolteae in individuals with low QASD score, which strongly mediates the increases in secondary bile acids like isoursodeoxycholate sulfate, a serum biomarker associated to post-prandial lipemia, inflammation and worse hepatic function 65 .…”

“…It is for example remarkable to observe that even in the subject group with the more dysbiotic microbiome (e.g., people with severe obesity), the higher the QASD score, the higher gut microbiome gene richness was. Among these, high-impact mediations explainging more than 20% of the QASD score's effect on serum metabolome involved 27 MGS and 21 metabolites, including some the above cited MGS like the increase in C. bolteae in individuals with low QASD score, which strongly mediates the increases in secondary bile acids like isoursodeoxycholate sulfate, a serum biomarker associated to post-prandial lipemia, inflammation and worse hepatic function 46 . Similar mediation analyses on individual dietary variables derived from FFQ data, the microbiome and plasma metabolomics have evidenced mediation relationships where a dietary factors impact plasma metabolite levels mediated by microbiome features (as we observe with our QASD score) like a mediating role of Ruminococcus species vSV on the effect of fruit consumption on plasma levels or urolithin B, but also multiple mediations in the opposite direction, where a dietary factor impacts microbiome features mediated by plasma metabolites, like a mediating role of plasma hippurate on the impact of coffee intake on the archaeon Methanobrevibacter smithii 60 .…”

“…In individuals with low QASD scores, significant positive mediations involved secondary bile acids. For instance, isoursodeoxycholate sulfate, a recent serum biomarker associated with post-prandial lipemia, inflammation, and impaired liver function 46 , had 25.2% of its increase in individuals with low QASD scores directly mediated by the increased abundances of CAG01263: [Clostridium] bolteae ATCC BAA-613 (Figure 6D). To support a potential mechanistic explanation for this causal mediation, the genome-scale metabolic models of C. bolteae from the AGORA2 repository, including the ATCC_BAA_613 strain, contain bile salt hydrolases capable of deconjugate the primary bile acids taurochenodeoxycholate and glycochenodeoxycholate by releasing taurine and glycine moieties respectively, from which the isoursocholate precursor ursodeoxycholate are produced 47,48 .…”