Abstract Objective: Emerging evidence implicates the gut microbiome in colorectal cancer development, with psychosocial stress recognized as a potential modulator of microbial composition and function. This study examines the association between hair cortisol concentration, a long-term, objective biomarker of chronic stress and gut microbiome profiles among racially diverse adults in Chicago, IL. Methods: A total of 56 adults aged 45–75 were enrolled from two urban academic medical centers in the Chicago metropolitan area between 2017 and early 2020. Biological samples (stool and hair), anthropometric measures, dietary intake (via two 24-hour recalls) and lifestyle data were obtained. Participant addresses were geocoded and integrated with neighborhood variables to situate psychosocial stress within the broader neighborhood socio-environmental characteristics. Fecal bile acids were quantified using LC/ESI-MS/MS. Cortisol levels in hair were measured via immunoassay, with ≥4.1 pg/mg indicating elevated stress based on the median cutoff of the study cohort. Stool metagenomic data were used to identify group-based variations in microbial diversity, taxonomic features, KEGG orthologs and functional enrichment analyses were performed using R statistical packages. Results were adjusted for false discovery rate. Results: The cohort was 64% female and 49% African American/Black, with mean age and BMI of 60 (± 6.1) years and 30 ± 6.9 kg/m2, respectively. Individuals with hair cortisol concentration at ≥ 4.1 pg/mg were more likely to self-identify as non-Hispanic Black and reside in neighborhood areas affected by significant socio-structural inequities, including higher rates of poverty, food insecurity, violence, and mortality, had higher body mass index, higher intake of taurine, and reported significantly lower dietary calcium intake per 1000 kcal. While we did not observe differences in total fecal bile acids, unconjugated primary bile acids, cholic acid and chenodeoxycholic acid, as well as taurine conjugated chenodeoxycholic acid were increased among the participants with elevated hair cortisol concentration (p 0.05). Our results also showed that isoallodeoxycholic acid, isoallolithocholic acid, and isolithocholic acid were significantly lower among individuals with elevated hair cortisol. Bacteria with genes capable of taurine conjugated bile acid metabolism, including Parabacteroides, Bacteroides, and Bifidobacterium were increased among participants with increased hair cortisol concentration. Conclusions: Elevated hair cortisol is associated with distinct gut microbial signatures characterized by taxa implicated in colorectal cancer risk. Our findings indicate that chronic psychosocial stress may partly contribute to colorectal cancer risk via gut microbiome alterations, especially among racially diverse, urban populations exposed to social and structural stressors. Further studies are needed to explore causal mechanisms and whether stress-reducing interventions can shift microbiome profiles toward a more protective state. Citation Format: Pius Sarfo. Buobu, Jellie Corduroy, Caitlin Welsh, Hanchu Dai, Manoela Lima. Oliveira, Mark Maienschein-Cline, Paul Grippo, H Rex Gaskins, Jason M. Ridlon, Chris Greening, Lisa Tussing-Humphreys, Patricia G Wolf. Increased hair cortisol is associated with intestinal microbial signatures implicated in colorectal cancer abstract. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr A113.
Buobu et al. (Thu,) studied this question.