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

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Correa, Renan Oliveira ; Castro, Pollyana Ribeiro ; Fachi, Jose Luis ; Nirello, Vinicius Dias ; El-Sahhar, Salma ; Imada, Shinya ; Pereira, Gabriel Vasconcelos ; Pral, Lais Passariello ; Pereira Araujo, Nathalia Vitoria ; Fernandes, Mariane Font ; Matheus, Valquiria Aparecida ; de Souza Felipe, Jaqueline ; dos Santos Pereira Gomes, Arilson Bernardo ; de Oliveira, Sarah ; de Rezende Rodovalho, Vinicius ; Machado de Oliveira, Samantha Roberta ; de Assis, Helder Carvalho ; Oliveira, Sergio Costa ; Dos Santos Martins, Flaviano ; Martens, Eric ; Colonna, Marco ; Varga-Weisz, Patrick ; Ramirez Vinolo, Marco Aurelio

• Document type: Journal article
• Source: MICROBIOME; v. 11, n. 1, p. 25-pg., 2023-04-26.

Abstract

Background The 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. Methods Mice 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. Results We 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 d 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. Conclusion This 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,.gamma delta 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. (AU)

• FAPESP's process: 16/23142-3 - Interaction between HIF-1 and short-chain fatty acids in the intestine: what is the role of HIF-1 acetylation?
• Grantee: Renan Oliveira Corrêa
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 21/06572-2 - Chromatin remodelling in Colitis in intestinal epithelial cells
• Grantee: Gabriel Vasconcelos Pereira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/06372-3 - Multiparametric flow cytometry
• Grantee: Alessandro dos Santos Farias
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 19/16113-5 - Chromatin dynamics in host-microbiome crosstalk in health and disease
• Grantee: Patrick Daniel Varga-Weisz
• Support Opportunities: Research Projects - SPEC Program
• FAPESP's process: 19/02640-3 - Role of the high-fiber diet on the function of the intestinal stem cells and their niche
• Grantee: Renan Oliveira Corrêa
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 18/15313-8 - Investigation of the molecular mechanisms involved in the interaction between microbiota-derived metabolites and host cells during inflammation
• Grantee: Marco Aurélio Ramirez Vinolo
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 20/02919-5 - Effect of inulin and Short-Chain Fatty Acids (SCFAs) on Hypoxia-Inducible Factor 1 (HIF-1) and its target genes in epithelial cells and intestinal stem cells
• Grantee: Pollyana Ribeiro Castro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/16280-3 - Role of the interaction between HIF-1 and the short chain fatty acids in the colon in physiological and pathologycal conditions (intestinal inflammation)
• Grantee: Marco Aurélio Ramirez Vinolo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/14071-0 - Multi-user Equipment approved in grant 19/16113-5: Chromium Controller & Next GEM Accessory Kit
• Grantee: Patrick Daniel Varga-Weisz
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 21/00393-9 - Role of histone acylations in linking gene expression to cellular metabolism in the gut
• Grantee: Vinícius Dias Nirello
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 17/06577-9 - Mechanisms involved in the protective effect of short-chain fatty acids against Clostridium difficile-associated colitis
• Grantee: José Luís Fachi
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/13689-0 - The role of histone crotonylation in intestinal stem cells
• Grantee: Laís Passariello Pral
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 21/05269-4 - Identification of histone crotonylation specific chromatin remodeling mechanisms in intestinal cells
• Grantee: Nathália Vitória Pereira Araújo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/02312-3 - Study of the effect of short-chain fatty acids on the tissue regeneration process during experimental colitis
• Grantee: Arilson Bernardo dos Santos Pereira Gomes
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 18/10165-0 - Role of microbiota-derived metabolites, the short-chain fatty acids, on innate lymphoid cells
• Grantee: José Luís Fachi
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 20/00311-0 - Role of ³´ T cells in adaptations of intestinal epithelium induced by inulin diet
• Grantee: Helder Carvalho de Assis
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)