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      The immune and microbial homeostasis determines the Candida–mast cells cross-talk in celiac disease

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          Abstract

          This study shows that the restoration of immune and microbial homeostasis promotes a beneficial Candida albicans–MC cross-talk attenuating the intestinal pathology in celiac disease.

          Abstract

          Celiac disease (CD) is an autoimmune enteropathy resulting from an interaction between diet, genome, and immunity. Although many patients respond to a gluten-free diet, in a substantive number of individuals, the intestinal injury persists. Thus, other factors might amplify the ongoing inflammation. Candida albicans is a commensal fungus that is well adapted to the intestinal life. However, specific conditions increase Candida pathogenicity. The hypothesis that Candida may be a trigger in CD has been proposed after the observation of similarity between a fungal wall component and two CD-related gliadin T-cell epitopes. However, despite being implicated in intestinal disorders, Candida may also protect against immune pathologies highlighting a more intriguing role in the gut. Herein, we postulated that a state of chronic inflammation associated with microbial dysbiosis and leaky gut are favorable conditions that promote C. albicans pathogenicity eventually contributing to CD pathology via a mast cells (MC)-IL-9 axis. However, the restoration of immune and microbial homeostasis promotes a beneficial C. albicans–MC cross-talk favoring the attenuation of CD pathology to alleviate CD pathology and symptoms.

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          From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites.

          A compelling set of links between the composition of the gut microbiota, the host diet, and host physiology has emerged. Do these links reflect cause-and-effect relationships, and what might be their mechanistic basis? A growing body of work implicates microbially produced metabolites as crucial executors of diet-based microbial influence on the host. Here, we will review data supporting the diverse functional roles carried out by a major class of bacterial metabolites, the short-chain fatty acids (SCFAs). SCFAs can directly activate G-coupled-receptors, inhibit histone deacetylases, and serve as energy substrates. They thus affect various physiological processes and may contribute to health and disease.
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            Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22.

            Endogenous tryptophan (Trp) metabolites have an important role in mammalian gut immune homeostasis, yet the potential contribution of Trp metabolites from resident microbiota has never been addressed experimentally. Here, we describe a metabolic pathway whereby Trp metabolites from the microbiota balance mucosal reactivity in mice. Switching from sugar to Trp as an energy source (e.g., under conditions of unrestricted Trp availability), highly adaptive lactobacilli are expanded and produce an aryl hydrocarbon receptor (AhR) ligand-indole-3-aldehyde-that contributes to AhR-dependent Il22 transcription. The resulting IL-22-dependent balanced mucosal response allows for survival of mixed microbial communities yet provides colonization resistance to the fungus Candida albicans and mucosal protection from inflammation. Thus, the microbiota-AhR axis might represent an important strategy pursued by coevolutive commensalism for fine tuning host mucosal reactivity contingent on Trp catabolism. Copyright © 2013 Elsevier Inc. All rights reserved.
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              Potential beneficial effects of butyrate in intestinal and extraintestinal diseases

              The multiple beneficial effects on human health of the short-chain fatty acid butyrate, synthesized from non-absorbed carbohydrate by colonic microbiota, are well documented. At the intestinal level, butyrate plays a regulatory role on the transepithelial fluid transport, ameliorates mucosal inflammation and oxidative status, reinforces the epithelial defense barrier, and modulates visceral sensitivity and intestinal motility. In addition, a growing number of studies have stressed the role of butyrate in the prevention and inhibition of colorectal cancer. At the extraintestinal level, butyrate exerts potentially useful effects on many conditions, including hemoglobinopathies, genetic metabolic diseases, hypercholesterolemia, insulin resistance, and ischemic stroke. The mechanisms of action of butyrate are different; many of these are related to its potent regulatory effects on gene expression. These data suggest a wide spectrum of positive effects exerted by butyrate, with a high potential for a therapeutic use in human medicine.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: SupervisionRole: ValidationRole: InvestigationRole: MethodologyRole: Writing—original draftRole: Project administrationRole: ConceptualizationRole: Data curationRole: Formal analysisRole: SupervisionRole: ValidationRole: InvestigationRole: MethodologyRole: Writing—original draftRole: Project administrationRole: ConceptualizationRole: Data curationRole: Formal analysisRole: SupervisionRole: ValidationRole: InvestigationRole: MethodologyRole: Writing—original draftRole: Project administration
                Role: InvestigationRole: Methodology
                Role: InvestigationRole: Methodology
                Role: InvestigationRole: Methodology
                Role: InvestigationRole: MethodologyRole: InvestigationRole: MethodologyRole: InvestigationRole: Methodology
                Role: InvestigationRole: MethodologyRole: InvestigationRole: MethodologyRole: InvestigationRole: Methodology
                Role: InvestigationRole: Methodology
                Role: InvestigationRole: MethodologyRole: InvestigationRole: Methodology
                Role: InvestigationRole: MethodologyRole: InvestigationRole: Methodology
                Role: InvestigationRole: MethodologyRole: InvestigationRole: MethodologyRole: InvestigationRole: Methodology
                Role: ValidationRole: InvestigationRole: MethodologyRole: ValidationRole: InvestigationRole: MethodologyRole: ValidationRole: InvestigationRole: Methodology
                Role: InvestigationRole: Methodology
                Role: ValidationRole: InvestigationRole: MethodologyRole: ValidationRole: InvestigationRole: MethodologyRole: ValidationRole: InvestigationRole: Methodology
                Role: Data curationRole: ValidationRole: InvestigationRole: VisualizationRole: MethodologyRole: Data curationRole: ValidationRole: InvestigationRole: VisualizationRole: MethodologyRole: Data curationRole: ValidationRole: InvestigationRole: VisualizationRole: Methodology
                Role: ConceptualizationRole: SupervisionRole: Funding acquisitionRole: ValidationRole: Writing—original draftRole: ConceptualizationRole: SupervisionRole: Funding acquisitionRole: ValidationRole: Writing—original draft
                Journal
                Life Sci Alliance
                Life Sci Alliance
                lsa
                lsa
                Life Science Alliance
                Life Science Alliance LLC
                2575-1077
                8 May 2024
                July 2024
                8 May 2024
                : 7
                : 7
                : e202302441
                Affiliations
                [1 ] Department of Medicine and Surgery, University of Perugia ( https://ror.org/00x27da85) , Perugia, Italy;
                [2 ] Mass Spectrometry Centre (CISM), University of Florence, Florence, Italy;
                [3 ] Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy;
                [4 ] European Institute for Research in Cystic Fibrosis (IERFC-Onlus), San Raffaele Scientific Institute, Milan, Italy;
                [5 ] Department of Pharmaceutical Sciences, University of Perugia ( https://ror.org/00x27da85) , Perugia, Italy;
                Author notes
                Author information
                https://orcid.org/0000-0002-9762-6493
                https://orcid.org/0000-0002-9896-171X
                https://orcid.org/0000-0003-3103-3924
                https://orcid.org/0000-0002-8570-6111
                https://orcid.org/0000-0003-4858-4853
                https://orcid.org/0000-0003-3007-0475
                https://orcid.org/0000-0001-5043-7233
                https://orcid.org/0000-0003-4432-1562
                https://orcid.org/0000-0001-7604-0189
                https://orcid.org/0000-0002-1433-7830
                https://orcid.org/0000-0002-7553-0159
                https://orcid.org/0000-0002-1356-525X
                Article
                LSA-2023-02441
                10.26508/lsa.202302441
                11079604
                38719750
                897eecec-daa7-4b16-89ac-e1feebd5a425
                © 2024 Renga et al.

                This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).

                History
                : 17 October 2023
                : 29 April 2024
                : 29 April 2024
                Funding
                Funded by: Fondazione Celiachia (FC), DOI http://dx.doi.org/10.13039/501100014566;
                Award ID: 008_FC_2018
                Award Recipient :
                Funded by: EC | Horizon 2020 Framework Programme (H2020), DOI http://dx.doi.org/10.13039/100010661;
                Award ID: 847507
                Award Recipient :
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