Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability
Patrice D. Cani,Sam Possemiers,T. Van de Wiele,Yves Guiot,Amandine Everard,O. Rottier,Lucie Geurts,Damien Naslain,Audrey M. Neyrinck,Didier M. Lambert,Giulio G. Muccioli,Nathalie M. Delzenne +11 more
TLDR
It is found that a selective gut microbiota change controls and increases endogenous GLP-2 production, and consequently improves gut barrier functions by a GLP1-2-dependent mechanism, contributing to the improvement of Gut barrier functions during obesity and diabetes.Abstract:
BACKGROUND AND AIMS: Obese and diabetic mice display enhanced intestinal permeability and metabolic endotoxaemia that participate in the occurrence of metabolic disorders. Our recent data support the idea that a selective increase of Bifidobacterium spp. reduces the impact of high-fat diet-induced metabolic endotoxaemia and inflammatory disorders. Here, we hypothesised that prebiotic modulation of gut microbiota lowers intestinal permeability, by a mechanism involving glucagon-like peptide-2 (GLP-2) thereby improving inflammation and metabolic disorders during obesity and diabetes. METHODS: Study 1: ob/ob mice (Ob-CT) were treated with either prebiotic (Ob-Pre) or non-prebiotic carbohydrates as control (Ob-Cell). Study 2: Ob-CT and Ob-Pre mice were treated with GLP-2 antagonist or saline. Study 3: Ob-CT mice were treated with a GLP-2 agonist or saline. We assessed changes in the gut microbiota, intestinal permeability, gut peptides, intestinal epithelial tight-junction proteins ZO-1 and occludin (qPCR and immunohistochemistry), hepatic and systemic inflammation. RESULTS: Prebiotic-treated mice exhibited a lower plasma lipopolysaccharide (LPS) and cytokines, and a decreased hepatic expression of inflammatory and oxidative stress markers. This decreased inflammatory tone was associated with a lower intestinal permeability and improved tight-junction integrity compared to controls. Prebiotic increased the endogenous intestinotrophic proglucagon-derived peptide (GLP-2) production whereas the GLP-2 antagonist abolished most of the prebiotic effects. Finally, pharmacological GLP-2 treatment decreased gut permeability, systemic and hepatic inflammatory phenotype associated with obesity to a similar extent as that observed following prebiotic-induced changes in gut microbiota. CONCLUSION: We found that a selective gut microbiota change controls and increases endogenous GLP-2 production, and consequently improves gut barrier functions by a GLP-2-dependent mechanism, contributing to the improvement of gut barrier functions during obesity and diabetes.read more
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Host-Gut Microbiota Metabolic Interactions
Jeremy K. Nicholson,Elaine Holmes,James Kinross,Rémy Burcelin,Glenn R. Gibson,Wei Jia,Sven Pettersson +6 more
TL;DR: A deeper understanding of the axes that physiologically connect the gut, liver, muscle, and brain are a prerequisite for optimizing therapeutic strategies to manipulate the gut microbiota to combat disease and improve health.
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Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity
Amandine Everard,Clara Belzer,Lucie Geurts,Janneke P. Ouwerkerk,Céline Druart,Laure B. Bindels,Yves Guiot,Muriel Derrien,Giulio G. Muccioli,Nathalie M. Delzenne,Willem M. de Vos,Willem M. de Vos,Patrice D. Cani +12 more
TL;DR: Substantial insight is provided into the intricate mechanisms of bacterial regulation of the cross-talk between the host and gut microbiota and provides a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.
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The impact of the gut microbiota on human health: an integrative view.
TL;DR: It is suggested that a holistic approach to studying the microbiota that goes beyond characterization of community composition and encompasses dynamic interactions between all components of the microbiota and host tissue over time will be crucial for building predictive models for diagnosis and treatment of diseases linked to imbalances in the microbiota.
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Gut Microbiota in Human Adults with Type 2 Diabetes Differs from Non-Diabetic Adults
Nadja Larsen,Finn K. Vogensen,Frans van den Berg,Dennis Sandris Nielsen,Anne Sofie Andreasen,Bente Klarlund Pedersen,Waleed Abu Al-Soud,Søren J. Sørensen,Lars Hestbjerg Hansen,Mogens Jakobsen +9 more
TL;DR: The results of this study indicate that type 2 diabetes in humans is associated with compositional changes in intestinal microbiota and the level of glucose tolerance should be considered when linking microbiota with metabolic diseases such as obesity and developing strategies to control metabolic diseases by modifying the gut microbiota.
Journal ArticleDOI
Metabolic Syndrome and Altered Gut Microbiota in Mice Lacking Toll-Like Receptor 5
Matam Vijay-Kumar,Jesse D. Aitken,Frederic A. Carvalho,Tyler C. Cullender,Simon M. Mwangi,Shanthi Srinivasan,Shanthi V. Sitaraman,Rob Knight,Ruth E. Ley,Andrew T. Gewirtz +9 more
TL;DR: Results support the emerging view that the gut microbiota contributes to metabolic disease and suggest that malfunction of the innate immune system may promote the development of metabolic syndrome.
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Obesity alters gut microbial ecology
Ruth E. Ley,Fredrik Bäckhed,Peter J. Turnbaugh,Catherine A. Lozupone,Robin D. Knight,Jeffrey I. Gordon +5 more
TL;DR: Analysis of the microbiota of genetically obese ob/ob mice, lean ob/+ and wild-type siblings, and their ob/+ mothers, all fed the same polysaccharide-rich diet, indicates that obesity affects the diversity of the gut microbiota and suggests that intentional manipulation of community structure may be useful for regulating energy balance in obese individuals.
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The gut microbiota as an environmental factor that regulates fat storage
Fredrik Bäckhed,Hao Ding,Hao Ding,Ting Wang,Lora V. Hooper,Gou Young Koh,Andras Nagy,Clay F. Semenkovich,Jeffrey I. Gordon +8 more
TL;DR: In this article, the authors found that conventionalization of adult germ-free C57BL/6 mice with a normal microbiota harvested from the distal intestine (cecum) of conventionally raised animals produces a 60% increase in body fat content and insulin resistance within 14 days despite reduced food intake.
Journal ArticleDOI
Metabolic endotoxemia initiates obesity and insulin resistance
Patrice D. Cani,Jacques Amar,Miguel A. Iglesias,Marjorie Poggi,Claude Knauf,Delphine Bastelica,Audrey M. Neyrinck,Francesca Fava,Kieran Tuohy,Chantal Chabo,Aurélie Waget,Evelyne Delmée,Béatrice Cousin,Thierry Sulpice,Bernard Chamontin,Jean Ferrières,Jean-François Tanti,Glenn R. Gibson,Louis Casteilla,Nathalie M. Delzenne,Marie-Christine Alessi,Rémy Burcelin +21 more
TL;DR: It is concluded that the LPS/CD14 system sets the tone of insulin sensitivity and the onset of diabetes and obesity and lowering plasma LPS concentration could be a potent strategy for the control of metabolic diseases.
Journal ArticleDOI
Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice
Patrice D. Cani,Rodrigo Bibiloni,Claude Knauf,Aurélie Waget,Audrey M. Neyrinck,Nathalie M. Delzenne,Rémy Burcelin +6 more
TL;DR: It is found that changes of gut microbiota induced by an antibiotic treatment reduced metabolic endotoxemia and the cecal content of LPS in both high-fat–fed and ob/ob mice, demonstrating that changes in gut microbiota controls metabolic endotoxinemia, inflammation, and associated disorders by a mechanism that could increase intestinal permeability.
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