Altered bile acid metabolism in people with HIV correlates with systemic and intestinal inflammation

To examine associations between plasma bile acids, systemic and gut inflammation, and intestinal bile acid receptor expression in people with HIV (PWH).

Retrospective case-control study using paired plasma and colorectal biopsy samples from adults with and without HIV.

Samples from 31 PWH and 21 people without HIV (PWOH) were analyzed. Plasma bile acids were quantified by targeted liquid chromatography-mass spectrometry (LC-MS) and cytokines by multiplex assays. Bile acid receptors farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) were quantified in gut tissue by quantitative reverse-transcriptase (qRT)-PCR, and immunohistochemistry with digital image analysis to localize receptor expression. Intestinal inflammation was assessed by histopathology. Group comparisons, multivariable regression, and Pearson correlations were used to evaluate relationships among bile acids, inflammation, and receptor expression.

Decreased levels of the primary bile acid chenodeoxycholic acid [ P  < 0.001, false discovery rate (FDR) = 0.002] as well as decreased levels of conjugated secondary bile acids glycochenodeoxycholic acid ( P  < 0.001, FDR=0.001), and taurochenodeoxycholic acid ( P  = 0.007, FDR = 0.02), and glycoursodeoxycholic acid ( P  = 0.008, FDR = 0.02) were observed in PWH. Antiretroviral therapy may also be a contributor to bile acid alterations with decreased glycodeoxycholic acid ( P  = 0.02, FDR = 0.19). There was no difference in FXR expression in the gut, but PWH had higher TGR5 expression ( P  < 0.001), which correlated with intestinal inflammation histopathology scores ( r  = 0.56, P  = 0.004).

PWH had decreased plasma primary and secondary bile acids. In addition, PWH had higher TGR5 expression in the gut, which correlated with intestinal inflammation. Reduced anti-inflammatory bile acid signaling may be one potential mechanism contributing to ongoing inflammation in HIV.