Prolonged restraint stressor exposure in outbred CD-1 mice impacts microbiota, colonic inflammation, and short chain fatty acids

PLoS One. 2018 May 9;13(5):e0196961. doi: 10.1371/journal.pone.0196961. eCollection 2018.


Stressor-exposure has been shown to exacerbate inflammation and change the composition of the gastrointestinal microbiota; however stressor-induced effects on microbiota-derived metabolites and their receptors are unknown. Thus, bacterial-produced short chain fatty acids (SCFAs), as well as microbial community composition, were assessed in the colons of mice exposed to stress during infection with Citrobacter rodentium. Mice were exposed to overnight restraint on 7 consecutive nights, or left undisturbed as a control. After the first exposure of restraint, mice were orally challenged with C. rodentium or with vehicle. Microbial community composition was assessed using 16S rRNA gene sequencing and SCFA levels measured using gas chromatography-mass spectrometry (GC-MS). Pathogen levels and colonic inflammation were also assessed 6 days post-infection. Results demonstrated that the microbial community structure and SCFA production were significantly affected by both stressor exposure and C. rodentium-infection. Exposure to prolonged restraint in the absence of infection significantly reduced SCFAs (acetic acid, butyric acid, and propionic acid). Multiple bacterial taxa were affected by stressor exposure, with the relative abundance of Lactobacillus being significantly reduced and directly correlated with propionic acid. Lactobacillus abundances were inversely correlated with colonic inflammation, supporting the contention that Lactobacillus helps to regulate mucosal inflammatory responses. Our data indicates that restraint stressor can have significant effects on pathogen-induced colonic inflammation and suggest that stressor-induced changes in the microbiota, microbial-produced SCFAs and their receptors may be involved.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Citrobacter rodentium / pathogenicity
  • Colon / microbiology
  • Colon / pathology
  • Enterobacteriaceae Infections / genetics
  • Enterobacteriaceae Infections / microbiology*
  • Fatty Acids, Volatile / biosynthesis
  • Fatty Acids, Volatile / genetics
  • Gastrointestinal Microbiome / genetics*
  • Gastrointestinal Microbiome / physiology
  • Inflammation / genetics
  • Inflammation / microbiology*
  • Intestinal Mucosa / microbiology
  • Lactobacillus / genetics*
  • Lactobacillus / physiology
  • Mice
  • Microbiota / genetics
  • Microbiota / physiology
  • RNA, Ribosomal, 16S / genetics
  • Restraint, Physical / methods


  • Fatty Acids, Volatile
  • RNA, Ribosomal, 16S

Associated data

  • figshare/6201107.v1