Infection trains the host for microbiota-enhanced resistance to pathogens

Cell. 2021 Feb 4;184(3):615-627.e17. doi: 10.1016/j.cell.2020.12.011. Epub 2021 Jan 15.

Abstract

The microbiota shields the host against infections in a process known as colonization resistance. How infections themselves shape this fundamental process remains largely unknown. Here, we show that gut microbiota from previously infected hosts display enhanced resistance to infection. This long-term functional remodeling is associated with altered bile acid metabolism leading to the expansion of taxa that utilize the sulfonic acid taurine. Notably, supplying exogenous taurine alone is sufficient to induce this alteration in microbiota function and enhance resistance. Mechanistically, taurine potentiates the microbiota's production of sulfide, an inhibitor of cellular respiration, which is key to host invasion by numerous pathogens. As such, pharmaceutical sequestration of sulfide perturbs the microbiota's composition and promotes pathogen invasion. Together, this work reveals a process by which the host, triggered by infection, can deploy taurine as a nutrient to nourish and train the microbiota, promoting its resistance to subsequent infection.

Keywords: Citrobacter rodentium; Enterococcus faecalis; Klebsiella pneumoniae; aerobic respiration; bile acid; bismuth subsalicylate; colonization resistance; gut microbiome; hydrogen sulfide; taurine.

Publication types

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

MeSH terms

  • Animals
  • Bacterial Infections / immunology
  • Bacterial Infections / microbiology
  • Colony Count, Microbial
  • Gastrointestinal Microbiome* / drug effects
  • Host-Pathogen Interactions* / drug effects
  • Immunity
  • Mice, Inbred C57BL
  • Sulfides / metabolism
  • Taurine / pharmacology

Substances

  • Sulfides
  • Taurine