(OR22-01-23) Chronic Stress and Fecal Bile Acid Composition

Objectives: Bile acids (BA) are liver-derived steroid molecules involved in lipid digestion. Diet drives BA composition and intestinal secretion. Typically, 90-95% of BAs are reabsorbed through enterohepatic circulation. However, there is evidence in animal models that chronic stress and downstream increases in cortisol can disrupt BA metabolism such that fewer BAs are reabsorbed and more enter the colon. The gut microbiota metabolizes BAs that escape reabsorption to secondary BAs and other metabolites that may be implicated in colorectal carcinogenesis. The objective is to examine the relationship between hair cortisol concentration, a marker of chronic stress, and fecal BA metabolites among urban adults.

Methods: Fifty-seven participants were recruited. Stool, hair, anthropometrics, and survey data were collected. Fecal BA profiling was completed using LC/MS. Hair cortisol concentration was examined via immunoassay. Participants were stratified on the median split of hair cortisol concentration ( >4.1pg/mg). Diet quality was calculated using USDA’s Healthy Eating Index-2015. Descriptive and inferential statistics were conducted.

Results: Participants were 64% female, 49% African American, and with mean age of 60 (± 6.1) years. Individuals with elevated hair cortisol ( >4.1pg/mg) were significantly more likely to self-identify as African American and with obesity. Elevated hair cortisol was associated with higher concentrations of conjugated and unconjugated primary BAs in the fecal stream [(e.g., cholic acid:1.75±4.62vs.0.05±0.05 μmol/100 mg dry stool and chenodeoxycholic acid 1.37±4.1vs.0.05±0.07 μmol/100 mg dry stool). Elevated hair cortisol was also associated with significantly lower (p < 0.05) fecal secondary BA derivatives involved in mucosal T-reg expansion. In multivariable modeling, hair cortisol (continuous) was a significant positive predictor of fecal concentrations of cholic acid and chenodeoxycholic acid when controlling for BMI, diet quality and race.

Conclusions: Chronic stress is characterized by a fecal stream enriched for primary BAs and depleted in anti-inflammatory secondary BA metabolites. Chronic stress may be an important target in the context of a multiprong lifestyle approach for optimizing host-microbial BA metabolism for CRC prevention.

Funding Sources: U54MD012523-01, Sub-Project ID: 7086; R01CA204808