CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands
Bruno Lamas,Mathias L. Richard,Valentin Leducq,Hang-Phuong Pham,Marie-Laure Michel,Grégory Da Costa,Chantal Bridonneau,Sarah Jegou,Thomas W. Hoffmann,Jane M. Natividad,Loic Brot,Soraya Taleb,Soraya Taleb,Aurélie Couturier-Maillard,Isabelle Nion-Larmurier,Fatiha Merabtene,Philippe Seksik,Anne Bourrier,Jacques Cosnes,Bernhard Ryffel,Bernhard Ryffel,Laurent Beaugerie,Jean-Marie Launay,Philippe Langella,Ramnik J. Xavier,Harry Sokol +25 more
TLDR
In this article, a relationship between the host and the gut microbiota govern intestinal homeostasis is revealed, and the authors reveal that host genes affect the composition and function of the Gut microbiota, altering the production of microbial metabolites and intestinal inflammation.Abstract:
Complex interactions between the host and the gut microbiota govern intestinal homeostasis but remain poorly understood. Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. CARD9 promotes recovery from colitis by promoting interleukin (IL)-22 production, and Card9-/- mice are more susceptible to colitis. The microbiota is altered in Card9-/- mice, and transfer of the microbiota from Card9-/- to wild-type, germ-free recipients increases their susceptibility to colitis. The microbiota from Card9-/- mice fails to metabolize tryptophan into metabolites that act as aryl hydrocarbon receptor (AHR) ligands. Intestinal inflammation is attenuated after inoculation of mice with three Lactobacillus strains capable of metabolizing tryptophan or by treatment with an AHR agonist. Reduced production of AHR ligands is also observed in the microbiota from individuals with IBD, particularly in those with CARD9 risk alleles associated with IBD. Our findings reveal that host genes affect the composition and function of the gut microbiota, altering the production of microbial metabolites and intestinal inflammation.read more
Citations
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Metagenomic biomarker discovery and explanation
Nicola Segata,Jacques Izard,Levi Waldron,Dirk Gevers,Larisa Miropolsky,Wendy S. Garrett,Curtis Huttenhower +6 more
TL;DR: In this article, a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation is described and validated, which addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities.
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The Microbiota-Gut-Brain Axis
John F. Cryan,Kenneth J. O’Riordan,Caitlin S. M. Cowan,Kiran V. Sandhu,Thomaz F.S. Bastiaanssen,Marcus Boehme,Martín Gabriel Codagnone,Sofia Cussotto,Christine Fülling,Anna V. Golubeva,Katherine E. Guzzetta,Minal Jaggar,Caitriona M. Long-Smith,Joshua M. Lyte,Jason A. Martin,Alicia Molinero-Perez,Gerard M. Moloney,Emanuela Morelli,Enrique Morillas,Rory C. O'Connor,Joana S Cruz-Pereira,Veronica L. Peterson,Kieran Rea,Nathaniel L. Ritz,Eoin Sherwin,Simon Spichak,Emily M. Teichman,Marcel van de Wouw,Ana Paula Ventura-Silva,Shauna E. Wallace-Fitzsimons,Niall P. Hyland,Gerard Clarke,Timothy G. Dinan +32 more
TL;DR: Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.
Journal ArticleDOI
Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease
TL;DR: This review gathers the most recent advances concerning the central role of Trp metabolism in microbiota-host crosstalk in health and disease and aims to facilitate a better understanding of the pathogenesis of human diseases and open therapeutic opportunities.
Journal ArticleDOI
Gut microbiota and IBD: causation or correlation?
TL;DR: Current associations between IBD and dysbiosis are summarized, the role of the gut microbiota in the context of specific animal models of colitis is described, and the potential role of microbiota-focused interventions in the treatment of human IBD is discussed.
Journal ArticleDOI
Gut microbiome structure and metabolic activity in inflammatory bowel disease
Eric A. Franzosa,Eric A. Franzosa,Alexandra Sirota-Madi,Julian Avila-Pacheco,Nadine Fornelos,Henry J. Haiser,Stefan Reinker,Tommi Vatanen,A. Brantley Hall,Himel Mallick,Himel Mallick,Lauren J. McIver,Lauren J. McIver,Jenny Sauk,Robin G. Wilson,Betsy W. Stevens,Justin M. Scott,Kerry A. Pierce,Amy Deik,Kevin Bullock,Floris Imhann,Jeffrey A. Porter,Alexandra Zhernakova,Jingyuan Fu,Rinse K. Weersma,Cisca Wijmenga,Cisca Wijmenga,Clary B. Clish,Hera Vlamakis,Curtis Huttenhower,Curtis Huttenhower,Ramnik J. Xavier +31 more
TL;DR: Using metabolomics and shotgun metagenomics on stool samples from individuals with and without inflammatory bowel disease, metabolites, microbial species and genes associated with disease were identified and validated in an independent cohort, providing an improved understanding of perturbations of the microbiome–metabolome interface in IBD.
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