Maternal consumption of yoghurt activating the aryl hydrocarbon receptor increases group 3 innate lymphoid cells in murine offspring

ABSTRACT 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, i...

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Main Authors: Grégory Pimentel, Thomas Roder, Cornelia Bär, Sandro Christensen, Zahra Sattari, Cristina Kalbermatter, Ueli von Ah, Christelle A. M. Robert, Pierre Mateo, Rémy Bruggmann, Stephanie C. Ganal-Vonarburg, Guy Vergères
Format: Article
Language:English
Published: American Society for Microbiology 2024-12-01
Series:Microbiology Spectrum
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Online Access:https://journals.asm.org/doi/10.1128/spectrum.00393-24
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author Grégory Pimentel
Thomas Roder
Cornelia Bär
Sandro Christensen
Zahra Sattari
Cristina Kalbermatter
Ueli von Ah
Christelle A. M. Robert
Pierre Mateo
Rémy Bruggmann
Stephanie C. Ganal-Vonarburg
Guy Vergères
author_facet Grégory Pimentel
Thomas Roder
Cornelia Bär
Sandro Christensen
Zahra Sattari
Cristina Kalbermatter
Ueli von Ah
Christelle A. M. Robert
Pierre Mateo
Rémy Bruggmann
Stephanie C. Ganal-Vonarburg
Guy Vergères
author_sort Grégory Pimentel
collection DOAJ
description ABSTRACT 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 in vitro 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.IMPORTANCEKey progresses in the sequencing and functional annotation of microbial organisms have revolutionized research in the fields of human metabolism and food biotechnology. In particular, the gut microbiome is now recognized as an important mediator of the impact of nutrition on human metabolism. Annotated genomes of a large number of bacteria are now available worldwide, which selectively transform food through fermentation to produce specific bioactive compounds with the potential to modulate human health. A previous research has demonstrated that the maternal microbiota shapes the neonatal immune system. Similarly, this report shows that lactic acid bacteria can be selected to produce fermented food that can also modulate postnatal intestinal immunity.
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spelling doaj-art-2d24662aa74c4fca9ee5655d5a9b6f032025-08-20T02:19:12ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972024-12-01121210.1128/spectrum.00393-24Maternal consumption of yoghurt activating the aryl hydrocarbon receptor increases group 3 innate lymphoid cells in murine offspringGrégory Pimentel0Thomas Roder1Cornelia Bär2Sandro Christensen3Zahra Sattari4Cristina Kalbermatter5Ueli von Ah6Christelle A. M. Robert7Pierre Mateo8Rémy Bruggmann9Stephanie C. Ganal-Vonarburg10Guy Vergères11Agroscope, Schwarzenburgstrasse, Bern, SwitzerlandInterfaculty Bioinformatics Unit, University of Bern, Bern, SwitzerlandAgroscope, Schwarzenburgstrasse, Bern, SwitzerlandDepartment of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, Bern, SwitzerlandAgroscope, Schwarzenburgstrasse, Bern, SwitzerlandDepartment of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, Bern, SwitzerlandAgroscope, Schwarzenburgstrasse, Bern, SwitzerlandInstitute of Plant Sciences, University of Bern, Switzerland, BernInstitute of Plant Sciences, University of Bern, Switzerland, BernInterfaculty Bioinformatics Unit, University of Bern, Bern, SwitzerlandDepartment of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, Bern, SwitzerlandAgroscope, Schwarzenburgstrasse, Bern, SwitzerlandABSTRACT 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 in vitro 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.IMPORTANCEKey progresses in the sequencing and functional annotation of microbial organisms have revolutionized research in the fields of human metabolism and food biotechnology. In particular, the gut microbiome is now recognized as an important mediator of the impact of nutrition on human metabolism. Annotated genomes of a large number of bacteria are now available worldwide, which selectively transform food through fermentation to produce specific bioactive compounds with the potential to modulate human health. A previous research has demonstrated that the maternal microbiota shapes the neonatal immune system. Similarly, this report shows that lactic acid bacteria can be selected to produce fermented food that can also modulate postnatal intestinal immunity.https://journals.asm.org/doi/10.1128/spectrum.00393-24aryl hydrocarbon receptorlactic acid bacterianewborn immunity
spellingShingle Grégory Pimentel
Thomas Roder
Cornelia Bär
Sandro Christensen
Zahra Sattari
Cristina Kalbermatter
Ueli von Ah
Christelle A. M. Robert
Pierre Mateo
Rémy Bruggmann
Stephanie C. Ganal-Vonarburg
Guy Vergères
Maternal consumption of yoghurt activating the aryl hydrocarbon receptor increases group 3 innate lymphoid cells in murine offspring
Microbiology Spectrum
aryl hydrocarbon receptor
lactic acid bacteria
newborn immunity
title Maternal consumption of yoghurt activating the aryl hydrocarbon receptor increases group 3 innate lymphoid cells in murine offspring
title_full Maternal consumption of yoghurt activating the aryl hydrocarbon receptor increases group 3 innate lymphoid cells in murine offspring
title_fullStr Maternal consumption of yoghurt activating the aryl hydrocarbon receptor increases group 3 innate lymphoid cells in murine offspring
title_full_unstemmed Maternal consumption of yoghurt activating the aryl hydrocarbon receptor increases group 3 innate lymphoid cells in murine offspring
title_short Maternal consumption of yoghurt activating the aryl hydrocarbon receptor increases group 3 innate lymphoid cells in murine offspring
title_sort maternal consumption of yoghurt activating the aryl hydrocarbon receptor increases group 3 innate lymphoid cells in murine offspring
topic aryl hydrocarbon receptor
lactic acid bacteria
newborn immunity
url https://journals.asm.org/doi/10.1128/spectrum.00393-24
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