Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study.
Clara Depommier,Amandine Everard,Céline Druart,Hubert Plovier,Matthias Van Hul,Sara Vieira-Silva,Gwen Falony,Jeroen Raes,Dominique Maiter,Nathalie M. Delzenne,Marie de Barsy,Audrey Loumaye,Michel P. Hermans,Jean-Paul Thissen,Willem M. de Vos,Willem M. de Vos,Patrice D. Cani +16 more
TLDR
In this article, Akkermansia muciniphila, a gut microbe previously associated with metabolic health in preclinical models, is safe and well tolerated in humans and may improve metabolic parameters in overweight and obese patients.Abstract:
Metabolic syndrome is characterized by a constellation of comorbidities that predispose individuals to an increased risk of developing cardiovascular pathologies as well as type 2 diabetes mellitus1. The gut microbiota is a new key contributor involved in the onset of obesity-related disorders2. In humans, studies have provided evidence for a negative correlation between Akkermansia muciniphila abundance and overweight, obesity, untreated type 2 diabetes mellitus or hypertension3–8. Since the administration of A. muciniphila has never been investigated in humans, we conducted a randomized, double-blind, placebo-controlled pilot study in overweight/obese insulin-resistant volunteers; 40 were enrolled and 32 completed the trial. The primary end points were safety, tolerability and metabolic parameters (that is, insulin resistance, circulating lipids, visceral adiposity and body mass). Secondary outcomes were gut barrier function (that is, plasma lipopolysaccharides) and gut microbiota composition. In this single-center study, we demonstrated that daily oral supplementation of 1010 A. muciniphila bacteria either live or pasteurized for three months was safe and well tolerated. Compared to placebo, pasteurized A. muciniphila improved insulin sensitivity (+28.62 ± 7.02%, P = 0.002), and reduced insulinemia (−34.08 ± 7.12%, P = 0.006) and plasma total cholesterol (−8.68 ± 2.38%, P = 0.02). Pasteurized A. muciniphila supplementation slightly decreased body weight (−2.27 ± 0.92 kg, P = 0.091) compared to the placebo group, and fat mass (−1.37 ± 0.82 kg, P = 0.092) and hip circumference (−2.63 ± 1.14 cm, P = 0.091) compared to baseline. After three months of supplementation, A. muciniphila reduced the levels of the relevant blood markers for liver dysfunction and inflammation while the overall gut microbiome structure was unaffected. In conclusion, this proof-of-concept study (clinical trial no. NCT02637115) shows that the intervention was safe and well tolerated and that supplementation with A. muciniphila improves several metabolic parameters. Supplementation with Akkermansia muciniphila, a gut microbe previously associated with metabolic health in preclinical models, is safe and well tolerated in humans and may improve metabolic parameters in overweight and obese patients.read more
Citations
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Journal ArticleDOI
Gut microbiota in human metabolic health and disease.
Yong Fan,Oluf Pedersen +1 more
TL;DR: How the gut microbiota and derived microbial compounds may contribute to human metabolic health and to the pathogenesis of common metabolic diseases are discussed, and examples of microbiota-targeted interventions aiming to optimize metabolic health are highlighted.
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Gut Microbiome: Profound Implications for Diet and Disease
Ronald D. Hills,Benjamin Pontefract,Hillary R. Mishcon,Cody Black,Cody Black,Steven C. Sutton,Cory R. Theberge +6 more
TL;DR: The role of diet quality, carbohydrate intake, fermentable FODMAPs, and prebiotic fiber in maintaining healthy gut flora is reviewed and the implications are discussed for various conditions including obesity, diabetes, irritable bowel syndrome, inflammatory bowel disease, depression, and cardiovascular disease.
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Mucus barrier, mucins and gut microbiota: the expected slimy partners?
Paola Paone,Patrice D. Cani +1 more
TL;DR: Different aspects of the mucus layer are debated by focusing on its chemical composition, regulation of synthesis and degradation by the microbiota as well as some characteristics of the slime layer in both physiological and pathological situations.
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Gut microbiota and human NAFLD: disentangling microbial signatures from metabolic disorders
Judith Aron-Wisnewsky,Judith Aron-Wisnewsky,Chloé Vigliotti,Julia J. Witjes,Phuong Le,Adriaan G. Holleboom,Joanne Verheij,Max Nieuwdorp,Karine Clément +8 more
TL;DR: Discrepant microbiome signatures across studies could be linked to the heterogeneity of geographical regions, ethnicity, population characteristics, microbiome sequencing tools, NAFLD diagnostic tools, disease spectrum, drug consumption and circadian rhythm.
Journal ArticleDOI
Gut microbiota-derived metabolites as central regulators in metabolic disorders.
TL;DR: The key classes of microbiota-derived metabolites that are altered in metabolic diseases and their role in pathogenesis are defined to represent potential biomarkers for early diagnosis and prognosis as well as promising targets for the development of novel therapeutic tools for metabolic disorders.
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Metabolic endotoxemia initiates obesity and insulin resistance
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