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

Acute stress triggers the release of stress hormones such as cortisol, increasing stress reactivity and aiding post-stress recovery. Prior work in rodents revealed the modulating role of the gut microbiota in stress reactivity, but whether this is also the case in humans is unclear. Additionally, to what degree stress reactivity is tied to one's capacity to produce microbial metabolites such as short-chain fatty acids (SCFAs) is untested. To close this gap, we invited 80 healthy human adults to the laboratory who were either exposed to a well-established, standardized intervention that induced acute stress or to a non-stressful control condition (n = 40 per group). Changes in stress hormones were assessed from repeated saliva sampling. Stool samples were obtained at baseline, and the gut microbiota were characterized through 16S rRNA gene amplicon sequencing. We found that higher gut microbiota diversity was associated with lower cortisol stress reactivity and lower levels of subjectively experienced stress, but not faster post-stress recovery, across the individuals of the stress group. Moreover, lower cortisol stress reactivity was associated with a higher relative abundance of taxa that encode metabolic pathways for the production of butyrate, a key SCFA. These results are the first to highlight the role of gut microbial diversity and inferred butyrate production capacity in modulating stress reactivity in healthy adults, underscoring the microbiota's potential to buffer against the detrimental effects of acute stress.