Gut microbial diversity and inferred capacity to produce butyrate modulate cortisol reactivity following acute stress in healthy adults

Abstract Acute stress triggers the release of stress hormones such as cortisol, increasing stress reactivity and aiding post-stress recovery. Rodent studies revealed that stress reactivity is modulated by the gut microbiota, and few interventional studies have provided evidence for an effect on human cortisol dynamics. However, it remains unclear whether stress reactivity is related to interindividual variations in gut microbial composition and to one’s capacity to produce microbial metabolites such as short-chain fatty acids (SCFAs). To close this gap, we analyzed data from 74 healthy human adults who completed the study in the laboratory and were either exposed to a well-established, standardized intervention that induced acute stress or to a non-stressful control condition (n = 35/39 per stress/control group). Stool samples were obtained at baseline, and the gut microbiota were characterized through 16S rRNA gene amplicon sequencing. Cortisol changes were assessed from repeated saliva sampling, paralleled by measurements of subjectively experienced stress. We found that higher gut microbial alpha diversity was associated with higher cortisol and subjective stress reactivity across individuals of the stress group, but not in controls. Cortisol stress reactivity was also associated with the relative abundance of bacterial taxa inferred to encode metabolic pathways for the production of butyrate and propionate, two key SCFAs. The results are the first to highlight the link between gut microbial diversity, inferred SCFA production capacity, and the acute stress response in healthy adults, underscoring the microbiota’s potential to flexibly modulate human psychophysiology in the aftermath of stress. Competing Interest Statement The authors have declared no competing interest. Footnotes We identified two errors affecting the cortisol stress reactivity analyses. We corrected these issues, re-ran all analyses, added robustness checks, and updated the manuscript and supplementary materials accordingly.