4.8 Article

Infection trains the host for microbiota-enhanced resistance to pathogens

Journal

CELL
Volume 184, Issue 3, Pages 615-+

Publisher

CELL PRESS
DOI: 10.1016/j.cell.2020.12.011

Keywords

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Funding

  1. Intramural Research Programs of NIAID [1ZIAAI001115-11]
  2. NIDDK [1ZIADK054508-22]
  3. NCI Center for Cancer Research [1ZIABC011153-11]
  4. NHGRI [1ZIAHG000180-19]
  5. NIH Director's Challenge Innovation Award Program
  6. DDIR
  7. NIGMS Postdoctoral Research Associate Training (PRAT) Program [1FI2GM128736-01]
  8. NIH
  9. Pew Latin American Fellows Program
  10. Deutsche Forschungsgemeinschaft [HI 2088/1-1]
  11. Human Frontier Science Program [LT000191/2018]
  12. Cancer Research Institute Irvington Postdoctoral Fellowship Program

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The research shows that gut microbiota from previously infected hosts have enhanced resistance to infection, associated with altered bile acid metabolism and expansion of taxa that utilize taurine. The supply of exogenous taurine alone can induce this alteration and enhance resistance. Mechanistically, taurine potentiates the microbiota's production of sulfide, inhibiting cellular respiration and promoting resistance to pathogen invasion.
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.

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