Pubblicazioni

Introduction. Among bioactive microbial compounds, metabolites from the tryptophan pathway, and in particular indole derivatives, held promise considering their role in the gut immune homeostasis. Such property has been attributed to their ability to bind to the intestinal transcription factor Aryl Hydrocarbon Receptor (AhR), modulating IL22 production by intestinal group 3 innate lymphoid cells (ILC3). Interestingly, it has been shown in mice that gut microbiota indole derivatives of the pregnant mother could reach the intestinal epithelium of the foetus and neonate and drive the early postnatal ILC3 development by activating AhR. Apart from the gut microbiota, the production of such indole compounds has also been reported during milk fermentation by lactic acid bacteria (LAB). Indole derivatives were found in fermented dairy (yoghurt or cheese), as well as in blood of subjects having consumed these products, and therefore were proposed as biomarkers of fermented dairy intake. The aim of our study was to test, in germ-free pregnant mice, if the intake of a specific fermented dairy product could result in an activation the pups’ intestinal innate immune system. Methods. Genetic screening of 631 LAB from Agroscope’s collection was performed to select strains based on their potential to produce indoles compounds. A selection of 135 yoghurts were produced, their ability to activate AhR was evaluated in vitro and compared to that of a conventional yoghurt using HepG2-AhR-Luc cell line. The most efficient yoghurt, as well as a conventional yoghurt, were given as sterile pellets to germ-free pregnant mice (n=4) for 14 days and 10 days postnatal. The development of the innate immune system was evaluated in the pups (n=15) 14 days postnatal in the small intestine by flow cytometry. The experiment was replicated (n = 4 mice, n = 12 pups). Results. A significant increase in the frequency of NKp46+ILC3+ ILC3s was observed in the pups after consumption of the test yoghurt by the mothers compared to the conventional yogurt. The result was confirmed in the replicated experiment. Discussion/Conclusion. The selection of a specific LAB based on its genetic coverage of the indole pathway and its ability to produce a fermented dairy able to activate AhR was an effective approach to produce a yoghurt with immunomodulatory properties in the pups. In pregnant germ-free mice, the intake of fermented dairy products can be seen as a source of bioactive microbial compounds leading to a modulation of the innate immune development of the pups.