Gut‐brain axis serotonergic responses to acute stress exposure are microbiome‐dependent

• Published in: Neurogastroenterology and motility 2020-11, Vol.32 (11), p.e13881-n/a
• Main Authors: Lyte, Joshua M., Gheorghe, Cassandra E., Goodson, Michael S., Kelley‐Loughnane, Nancy, Dinan, Timothy G., Cryan, John F., Clarke, Gerard
• Format: Article
• Language: English
• Subjects: Colon; Colonization; Cortex (frontal); Digestive system; gastrointestinal; Gastrointestinal tract; Gene expression; germ‐free; Ileum; Intestinal microflora; Metabolites; Microbiomes; Microbiota; microbiota‐gut‐brain axis; neuroendocrine; Serotonin; Sex; stress
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/nmo.13881

Background Understanding the mechanisms underpinning the response to acute stress is critical for determining how this can be modulated in both health and disease and across sexes. Stress can markedly alter the microbiome and gut‐brain axis signaling with the serotonergic system being particularly sensitive to acute stress. As the impact of acute stress on regional serotonergic dynamics in the gut‐brain axis and the contribution of the microbiome to this are poorly appreciated, we used microbiota‐deficient mice to assess whether the serotonergic response to acute stress exposure is microbiome dependent. Methods Adult male and female conventional, germ‐free, and colonized germ‐free mice underwent a single acute stressor and samples were harvested immediately or 45 minutes following stress. Serotonin and related metabolites and serotonergic gene expression were determined. Key Results Our data clearly show the microbiota influenced gastrointestinal serotonergic response to acute stress in a sex‐ and region‐dependent manner. Male‐specific poststress increases in colonic serotonin were absent in germ‐free mice but normalized following colonization. mRNA serotonergic gene expression was differentially expressed in colon and ileum of germ‐free mice on a sex‐dependent basis. Within the frontal cortex, absence of the microbiome altered basal serotonin, its main metabolite 5‐hydroxyindoleacetic acid, and prevented stress‐induced increases in serotonin turnover. Conclusions and Inferences The gut microbiome influences the set points of the brain and gastrointestinal serotonergic systems and affected their response to acute stress in a sex‐ and region‐dependent manner. The gut microbiome influences the set point for the gut‐brain axis serotonergic system and also primes for the response to an acute stressor in a sex‐dependent manner. These findings offer a new window into host‐microbe dialogue and may have important functional and translational implications.