Pimentel, GrégoryGrégoryPimentelRoder, ThomasThomasRoder0000-0002-6642-6288Bär, CorneliaCorneliaBärChristensen, SandroSandroChristensenSattari, ZahraZahraSattariKalbermatter, CristinaCristinaKalbermattervon Ah, UeliUelivon AhRobert, Christelle A. M.Christelle A. M.RobertVergères, GuyGuyVergèresBruggmann, RémyRémyBruggmannGanal-Vonarburg, Stephanie C.Stephanie C.Ganal-VonarburgMateo, PierrePierreMateo0000-0003-4338-3024Laxmi Yeruva2024-11-152024-11-152024-10-29https://boris-portal.unibe.ch/handle/20.500.12422/189133Stephanie C. Ganal-Vonarburg and Guy Vergères contributed equally to this article.Indole derivatives are microbial metabolites of the tryptophan pathway involved in gut immune homeostasis. They bind to the aryl hydrocarbon receptor (AhR), thereby modulating development of intestinal group 3 innate lymphoid cells (ILC3) and subsequent interleukin-22 production. In mice, indole derivatives of the maternal microbiota can reach the milk and drive early postnatal ILC3 development. Apart from the gut microbiota, lactic acid bacteria (LAB) also produce indole compounds during milk fermentation. Using germ-free mice, the aim of our study was to test if maternal intake of a dairy product enriched in AhR-activating indoles produced by fermentation could boost maturation of the intestinal innate immune system in the offspring. A set of 631 LAB strains were genetically screened for their potential to produce indole compounds. Among these, 125 strains were tested in combination with standard strains to produce yoghurts that were screened for their ability to activate AhR using the HepG2–AhR–Luc cell line. The most active yoghurt and a control yoghurt were formulated as pellets and fed to germ-free dams during pregnancy and lactation. Analysis of the offspring on postnatal day 14 using flow cytometry revealed an increase in the frequency of small intestinal lamina propria NKp46 +ILC3 s in the pups born to dams that had consumed the purified diet containing an AhR-active yoghurt (AhrY-diet) compared to control yoghurt (ConY-diet). Selection of LABs based on their ability to produce a fermented dairy able to activate AhR appears to be an effective approach to produce a yoghurt with immunomodulatory properties.enaryl hydrocarbon receptorlactic acid bacterianewborn immunityarticle10.48620/762663947200510.1128/spectrum.00393-24