Inulin diet uncovers complex diet-microbiota-immune cell interactions remodeling the gut epithelium

Microbiome

Research

Sergio Costa Oliveira¹  Marco Colonna²  Nathália Vitoria Pereira Araújo³  Vinícius Dias Nirello³  Patrick Varga-Weisz⁴  Gabriel Vasconcelos Pereira⁵  Shinya Imada⁶  Flaviano Dos Santos Martins⁷  Samantha Roberta Machado de Oliveira⁷  Sarah de Oliveira⁸  Arilson Bernardo dos Santos Pereira Gomes⁸  Mariane Font Fernandes⁸  Vinícius de Rezende Rodovalho⁸  Helder Carvalho de Assis⁸  Pollyana Ribeiro Castro⁸  Jaqueline de Souza Felipe⁸  Valquíria Aparecida Matheus⁸  Laís Passariello Pral⁸  José Luís Fachi⁹  Marco Aurélio Ramirez Vinolo^1,10  Renan Oliveira Corrêa^1,11  Salma El-Sahhar^1,12  Eric Martens^1,13 

[1] Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil;Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, 05508-000, São Paulo, SP, Brazil;Department of Pathology and Immunology, Washington University School of Medicine, 63110, Saint Louis, MO, USA;International Laboratory for Microbiome Host Epigenetics, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, 13083-862, Campinas, SP, Brazil;International Laboratory for Microbiome Host Epigenetics, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, 13083-862, Campinas, SP, Brazil;School of Life Sciences, University of Essex, CO4 3SQ, Colchester, UK;São Paulo Excellence Chair, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, 13083-862, Campinas, SP, Brazil;International Laboratory for Microbiome Host Epigenetics, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, 13083-862, Campinas, SP, Brazil;University of Michigan Medical School, 48109, Ann Arbor, MI, USA;Koch Institute for Integrative Cancer Research at MIT, 02139, Cambridge, MA, USA;Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 734-8551, Hiroshima, Japan;Laboratory of Biotherapeutics Agents, Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil;Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, 13083-862, Campinas, SP, Brazil;Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, 13083-862, Campinas, SP, Brazil;Department of Pathology and Immunology, Washington University School of Medicine, 63110, Saint Louis, MO, USA;Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, 13083-862, Campinas, SP, Brazil;International Laboratory for Microbiome Host Epigenetics, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, 13083-862, Campinas, SP, Brazil;Experimental Medicine Research Cluster, 13083-862, Campinas, SP, Brazil;Obesity and Comorbidities Research Center (OCRC), University of Campinas, 13083-864, Campinas, SP, Brazil;Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, 13083-862, Campinas, SP, Brazil;Koch Institute for Integrative Cancer Research at MIT, 02139, Cambridge, MA, USA;School of Life Sciences, University of Essex, CO4 3SQ, Colchester, UK;University of Michigan Medical School, 48109, Ann Arbor, MI, USA;

关键词: Bacteroidales;    Epithelial remodeling;    Gut homeostasis;    High-fiber diet;    IL-22;    Intestinal stem cells;    γδ T cells;   

DOI  :  10.1186/s40168-023-01520-2

 received in 2022-08-29, accepted in 2023-03-16,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe continuous proliferation of intestinal stem cells followed by their tightly regulated differentiation to epithelial cells is essential for the maintenance of the gut epithelial barrier and its functions. How these processes are tuned by diet and gut microbiome is an important, but poorly understood question. Dietary soluble fibers, such as inulin, are known for their ability to impact the gut bacterial community and gut epithelium, and their consumption has been usually associated with health improvement in mice and humans. In this study, we tested the hypothesis that inulin consumption modifies the composition of colonic bacteria and this impacts intestinal stem cells functions, thus affecting the epithelial structure.MethodsMice were fed with a diet containing 5% of the insoluble fiber cellulose or the same diet enriched with an additional 10% of inulin. Using a combination of histochemistry, host cell transcriptomics, 16S microbiome analysis, germ-free, gnotobiotic, and genetically modified mouse models, we analyzed the impact of inulin intake on the colonic epithelium, intestinal bacteria, and the local immune compartment.ResultsWe show that the consumption of inulin diet alters the colon epithelium by increasing the proliferation of intestinal stem cells, leading to deeper crypts and longer colons. This effect was dependent on the inulin-altered gut microbiota, as no modulations were observed in animals deprived of microbiota, nor in mice fed cellulose-enriched diets. We also describe the pivotal role of γδ T lymphocytes and IL-22 in this microenvironment, as the inulin diet failed to induce epithelium remodeling in mice lacking this T cell population or cytokine, highlighting their importance in the diet-microbiota-epithelium-immune system crosstalk.ConclusionThis study indicates that the intake of inulin affects the activity of intestinal stem cells and drives a homeostatic remodeling of the colon epithelium, an effect that requires the gut microbiota, γδ T cells, and the presence of IL-22. Our study indicates complex cross kingdom and cross cell type interactions involved in the adaptation of the colon epithelium to the luminal environment in steady state.-dZ131ovLvfeoRbZ-Pz4qeVideo Abstract

【 授权许可】

CC BY   
© The Author(s) 2023. corrected publication 2023

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