February 2, 2021

Gut bacteria use nutrient to fight off germs

At a Glance

  • Research in mice showed that gut bacteria use an essential amino acid to protect the host from invading pathogens.
  • The results could aid efforts seeking alternatives to antibiotics.
Klebsiella pneumoniae on surface of human neutrophil Colorized scanning electron micrograph showing carbapenem-resistant Klebsiella pneumoniae interacting with a human neutrophil. NIAID

Trillions of microbes, like bacteria, fungi, and other microbes, are living on or in your body right now. Together, they make up your microbiota. Most don’t cause any harm. In fact, many protect you from harmful infections.

Bacteria live in colonies. This lets them work together to form defenses against other bacteria. But how they defend themselves from infiltrating bacteria isn’t fully understood. A better understanding of how they do so could help scientists find alternatives to antibiotics, which harm beneficial microbes and can become less effective as pathogens develop drug resistance.

A team of NIH scientists led by Drs. Apollo Stacey and Yasmine Belkaid of NIH’s National Institute of Allergy and Infectious Diseases (NIAID) used mice that had experienced prior infections to examine how this might change the way the microbiota fight off pathogens. The study was published on January 15, 2021 in Cell.

The researchers examined the microbes of mice who’d been infected with Yersinia pseudotuberculosis, a food-borne pathogen. After the mice recovered, the team tested their resistance to Klebsiella pneumoniae (Kpn). Kpn is harbored by healthy people in low levels; however, it’s also associated with life-threatening infections in hospitalized patients.

The researchers observed enhanced resistance to Kpn in mice four weeks after infection. This protection lasted for at least 15 weeks. It could also be transferred by giving the gut microbes from previously exposed mice to germ-free mice, suggesting a role for the microbiota.

Through analysis of the microbiota, the team identified a class of bacteria—Deltaproteobacteria—involved in fighting these infections. Further analysis led them to identify taurine as the trigger for Deltaproteobacteria activity. Taurine is an amino acid that helps the body digest fats and oils. It is found naturally in bile acids in the gut. The Deltaproteobacteria produce an antimicrobial compound from taurine called sulfide.

The team found that taurine given to mice as a supplement in drinking water also helped the microbiota to prevent infection. However, when mice drank water containing bismuth subsalicylate—a common over-the-counter drug used to treat diarrhea and upset stomach—infection protection waned because bismuth inhibits sulfide production.

The scientists believe that infection induces the body to alter bile production, increasing levels of taurine in the gut. This prompts gut microbes to produce high levels of sulfide to prevent colonization by pathogens.

“We discovered that hosts can adapt to infections by nourishing their gut microbiota with taurine, a strategy that serves to boost the microbiota’s production of sulfide and ensure its heightened resistance against future pathogen invasions,” says Belkaid.

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References: Infection trains the host for microbiota-enhanced resistance to pathogens. Stacy A, Andrade-Oliveira V, McCulloch JA, Hild B, Oh JH, Perez-Chaparro PJ, Sim CK, Lim AI, Link VM, Enamorado M, Trinchieri G, Segre JA, Rehermann B, Belkaid Y. Cell. 2021 Jan 15:S0092-8674(20)31681-0. doi: 10.1016/j.cell.2020.12.011. Online ahead of print. PMID: 33453153.

Funding: NIH’S National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Cancer Institute (NCI), National Human Genome Research Institute (NHGRI), National Institute of General Medical Sciences (NIGMS), and NIH Director’s Office; Pew Charitable Trusts; Deutsche Forschungsgemeinschaft; Human Frontier Science Program; Cancer Research Institute.