Commensal gut bacteria produce acetylcholine from dietary choline, enhancing mucosal IgA responses and infection resistance (nature.com)

• In vivo commensal metabolomes activated muscarinic ACh receptors, while in vitro counterparts did not, due to conversion of dietary choline.
• Bifidobacterium species (e.g., B. breve, B. longum) and Pediococcus pentosaceus produce ACh via novel hexapeptide repeat acetyltransferases.
• ACh-producing B. breve enhances intestinal IgA responses through nicotinic receptors and improves resistance to Salmonella infection.
• The study provides a publicly accessible interactive GPCR screening data portal for exploring in vitro vs in vivo metabolome activities.

"Using a multiplexed GPCR screening platform (PRESTO-Salsa), researchers compared bioactivities of 100 commensal strains grown in vitro versus in vivo in germ-free mice. In vivo metabolomes activated muscarinic acetylcholine receptors due to bacterial conversion of dietary choline to acetylcholine. Key producers included Bifidobacterium species and Pediococcus pentosaceus. Bacterial enzymes (hexapeptide repeat acetyltransferases) were identified. Mice colonized with ACh-producing B. breve showed increased intestinal IgA, altered microbiota, and enhanced resistance to Salmonella infection via nicotinic receptors."