Author information

1 Pediatric Gastroenterology, Nationwide Children's Hospital, Columbus, OH, United States.

2 Center for Microbial Pathogenesis, The Research Institute, Nationwide Children's Hospital, Columbus, OH, United States.

3 Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States.

4 Campus Chemical Instrumentation Center Mass Spec and Proteomics, The Ohio State University, Columbus, OH, United States.

5 Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine.

6 College of Nursing, The Ohio State University, Columbus, OH, United States.

7 Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, United States.

8 Bioinformatics Services Division, Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Kannapolis, NC, United States.

Abstract

OBJECTIVES: Gastrointestinal disorders, such as inflammatory bowel diseases (IBD) and functional gastrointestinal disorders (FGID), involve disrupted homeostatic interactions between the microbiota and the host. Both disorders are worsened during stress, and in laboratory mice, stress exposure has been shown to change the composition of the gut microbiome. Stress-induced changes to the microbiome exacerbate intestinal inflammation and alter intestinal motility in mice. However, it is not yet known whether microbiota-derived short chain fatty acids (butyrate, propionate, and acetate) and their receptors contribute to this effect.

METHODS: Mice were exposed to a social disruption (SDR) stress, or left undisturbed as a control. After the first stress exposure, mice were orally challenged with Citrobacter rodentium or with vehicle. The levels of SCFAs were measured using gas chromatography-mass spectrometry. SCFA receptors were measured via real time PCR. Microbial community composition was assessed using 16S rRNA gene sequencing.

RESULTS: Stress exposure reduced colonic SCFA levels. However, stress exposure and C. rodentium significantly increased SCFA levels and changed the expression of SCFA receptors. The levels of SCFAs did not correlate with the severity of colonic inflammation, but the colonic expression of the SCFA receptor GPR41 was positively associated with inflammatory cytokines and colonic histopathology scores. The relative abundances of several taxa of colonic bacteria were significantly changed by stress exposure, including SCFA producers.

CONCLUSIONS: Social stress can have a significant effect on infection-induced colonic inflammation, and stress-induced changes in microbial-produced metabolites and their receptors may be involved.