Dietary Fructose and Microbiota-Derived Short-Chain Fatty Acids Promote Bacteriophage Production in the Gut Symbiont Lactobacillus reuteri

• Published in: Cell host & microbe 2019-02, Vol.25 (2), p.273-284.e6
• Main Authors: Oh, Jee-Hwan, Alexander, Laura M., Pan, Meichen, Schueler, Kathryn L., Keller, Mark P., Attie, Alan D., Walter, Jens, van Pijkeren, Jan-Peter
• Format: Article
• Language: English
• Subjects: Animals; diet; Fatty Acids, Volatile - metabolism; fructose; Fructose - metabolism; Gastrointestinal Tract - microbiology; Gastrointestinal Tract - virology; gut symbiont; Lactobacillus reuteri; Lactobacillus reuteri - growth & development; Lactobacillus reuteri - metabolism; Lactobacillus reuteri - virology; Male; Metabolic Networks and Pathways - drug effects; Mice, Inbred C57BL; phage; prophage; Prophages - growth & development; SCFA; Stress, Physiological; sugar; Virus Activation
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2018.11.016

The mammalian intestinal tract contains a complex microbial ecosystem with many lysogens, which are bacteria containing dormant phages (prophages) inserted within their genomes. Approximately half of intestinal viruses are derived from lysogens, suggesting that these bacteria encounter triggers that promote phage production. We show that prophages of the gut symbiont Lactobacillus reuteri are activated during gastrointestinal transit and that phage production is further increased in response to a fructose-enriched diet. Fructose and exposure to short-chain fatty acids activate the Ack pathway, involved in generating acetic acid, which in turn triggers the bacterial stress response that promotes phage production. L. reuteri mutants of the Ack pathway or RecA, a stress response component, exhibit decreased phage production. Thus, prophages in a gut symbiont can be induced by diet and metabolites affected by diet, which provides a potential mechanistic explanation for the effects of diet on the intestinal phage community. [Display omitted] •Lactobacillus reuteri produces phage during gastrointestinal transit•Dietary fructose and SCFAs promote L. reuteri phage production•Fructose metabolism and SCFA exposure activate the Ack pathway•The Ack pathway promotes phage production in a RecA-dependent manner Oh et al. discover that the central carbon metabolism of the gut symbiont Lactobacillus reuteri is intimately connected to phage production. Dietary fructose or exposure to SCFAs activates the Ack pathway in Lactobacillus reuteri, which evokes a global stress response in the bacterium that consequently leads to increased phage production.