Transient Osmotic Perturbation Causes Long-Term Alteration to the Gut Microbiota

Cell. 2018 Jun 14;173(7):1742-1754.e17. doi: 10.1016/j.cell.2018.05.008.

Abstract

Osmotic diarrhea is a prevalent condition in humans caused by food intolerance, malabsorption, and widespread laxative use. Here, we assess the resilience of the gut ecosystem to osmotic perturbation at multiple length and timescales using mice as model hosts. Osmotic stress caused reproducible extinction of highly abundant taxa and expansion of less prevalent members in human and mouse microbiotas. Quantitative imaging revealed decimation of the mucus barrier during osmotic perturbation, followed by recovery. The immune system exhibited temporary changes in cytokine levels and a lasting IgG response against commensal bacteria. Increased osmolality prevented growth of commensal strains in vitro, revealing one mechanism contributing to extinction. Environmental availability of microbiota members mitigated extinction events, demonstrating how species reintroduction can affect community resilience. Our findings (1) demonstrate that even mild osmotic diarrhea can cause lasting changes to the microbiota and host and (2) lay the foundation for interventions that increase system-wide resilience.

Keywords: PEG; S24-7; diarrhea; immune monitoring; metagenomics; microbiome; microbiota; osmotic perturbation; proteomics; transcriptomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bacteroidetes / drug effects
  • Bacteroidetes / genetics
  • Bacteroidetes / isolation & purification
  • Cecum / chemistry
  • Cecum / metabolism
  • Cecum / microbiology
  • Cecum / pathology
  • Colon / chemistry
  • Colon / microbiology
  • Colon / pathology
  • Cytokines / metabolism
  • Diarrhea / immunology
  • Diarrhea / microbiology
  • Diarrhea / pathology*
  • Diarrhea / veterinary
  • Feces / microbiology
  • Gastrointestinal Microbiome / drug effects*
  • Glycoside Hydrolases / metabolism
  • Humans
  • Immunity, Humoral / drug effects
  • Immunoglobulin G / metabolism
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Metagenomics
  • Mice
  • Osmolar Concentration
  • Polyethylene Glycols / metabolism
  • Polyethylene Glycols / pharmacology*
  • Proteome / analysis
  • RNA, Ribosomal, 16S / chemistry
  • RNA, Ribosomal, 16S / genetics
  • Verrucomicrobia / drug effects
  • Verrucomicrobia / genetics
  • Verrucomicrobia / isolation & purification

Substances

  • Cytokines
  • Immunoglobulin G
  • Proteome
  • RNA, Ribosomal, 16S
  • Polyethylene Glycols
  • Glycoside Hydrolases
  • polyethylene glycol 3350