The microbiome is playing a very important role for its host by providing some protection against future infections. It is thought that this process, known as colonization resistance, can be shaped throughout the course of the host’s lifetime by different infections—but the process is not well understood. New work from researchers at the NIAID Microbiome Program at the National Institutes of Health (NIH) show that bacteria in the gut microbiota of hosts who had previous infections have enhanced resistance to infection. Further, their data suggest that taurine alone—an amino acid found naturally in some foods such as meat, fish, and eggs—could induce the enhance resistance of the microbiome. The finding could aid efforts seeking alternatives to antibiotics.

This work is published in Cell in a paper entitled, “Infection trains the host for microbiota-enhanced resistance to pathogens”.

Seeking out alternatives to antibiotics, which harm the microbiota and become less effective as bacteria develop drug resistance, is a key area of infectious disease research. Given the relatively recent appreciation of the role of the microbiome in multiple processes,  it is important to uncover the role that the microbiota plays in infections when finding or enhancing natural treatments to replace antibiotics.

In this study, researchers observed that microbiota that had experienced prior infection helped prevent infection with Klebsiella pneumoniae when transferred to germ-free mice. They found that infection induces host taurine production and the expansion of taurine utilizers. They went on to identify a class of bacteria—Deltaproteobacteria—involved in fighting these infections. The taurine, they determined, is the trigger for Deltaproteobacteria activity.

Although taurine is not not incorporated into proteins, it is highly abundant in the brain, retina, muscle tissue, and organs throughout the body. It is available as a supplement, and is even mixed into sports drinks based on unproven suggestions that it can increase athletic performance. Taurine helps the body digest fats and oils and is found naturally in bile acids in the gut. The poisonous gas hydrogen sulfide is a byproduct of taurine.

Mechanistically, the authors explain, taurine potentiates the microbiota’s production of sulfide, an inhibitor of cellular respiration, which is a key component to host invasion by numerous pathogens. Because of that, pharmaceutical sequestration of sulfide perturbs the microbiota’s composition and promotes pathogen invasion.

Sulfide sequestration, they suggest, “unleashes endogenous respirers” in the gut microbiota. The group’s data suggest that low levels of taurine allow pathogens to colonize the gut, but high levels produce enough hydrogen sulfide to prevent colonization.

The researchers found that a single, mild infection is sufficient to prepare the microbiota to resist subsequent infection, and that the liver and gallbladder, which synthesize and store bile acids containing taurine, can develop long-term infection protection.

Taurine, they found, given to mice as a supplement in drinking water prepared 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 hydrogen sulfide production.

Together, the authors note, 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.”

Graphical abstract Stacey et al.
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