<i>Akkermansia muciniphila</i>and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology

Dao, Maria Carlota; Everard, Amandine; Aron‐Wisnewsky, Judith; Sokolovska, Nataliya; Prifti, Edi; Verger, Eric O.; Kayser, Brandon D.; Levenez, Florence; Chilloux, Julien; Hoyles, Lesley; Dumas, Marc; Rizkalla, Salwa W.; Doré, Joël; Cani, Patrice D.; Clément, Karine

doi:10.1136/gutjnl-2014-308778

Cited by 1,482 publications

(1,223 citation statements)

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“…Recent findings suggest that a high-fat diet induces a significant decrease in Akkermansia bacteria (48), and increased Akkermansia is associated with improved glucose homeostasis in rodents (49). An Akkermansia-enriched microbial population also correlates with a healthier metabolic status and may contribute to the antidiabetic effects of metformin in the clinic (11). However, bile acid regulation of the gut microbiota remains unresolved.…”

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confidence: 99%

Activation of bile acid signaling improves metabolic phenotypes in high-fat diet-induced obese mice

Pierre

Martinez

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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EB, Yin DP. Activation of bile acid signaling improves metabolic phenotypes in high-fat diet-induced obese mice. Am J Physiol Gastrointest Liver Physiol 311: G286 -G304, 2016. First published June 23, 2016 doi:10.1152/ajpgi.00202.2016.-The metabolic benefits induced by gastric bypass, currently the most effective treatment for morbid obesity, are associated with bile acid (BA) delivery to the distal intestine. However, mechanistic insights into BA signaling in the mediation of metabolic benefits remain an area of study. The bile diversion () mouse model, in which the gallbladder is anastomosed to the distal jejunum, was used to test the specific role of BA in the regulation of glucose and lipid homeostasis. Metabolic phenotype, including body weight and composition, glucose tolerance, energy expenditure, thermogenesis genes, total BA and BA composition in the circulation and portal vein, and gut microbiota were examined. BD improves the metabolic phenotype, which is in accord with increased circulating primary BAs and regulation of enterohormones. BD-induced hypertrophy of the proximal intestine in the absence of BA was reversed by BA oral gavage, but without influencing BD metabolic benefits. BD-enhanced energy expenditure was associated with elevated TGR5, D2, and thermogenic genes, including UCP1, PRDM16, PGC-1␣, PGC-1␤, and PDGFR␣ in epididymal white adipose tissue (WAT) and inguinal WAT, but not in brown adipose tissue. BD resulted in an altered gut microbiota profile (i.e., Firmicutes bacteria were decreased, Bacteroidetes were increased, and Akkermansia was positively correlated with higher levels of circulating primary BAs). Our study demonstrates that enhancement of BA signaling regulates glucose and lipid homeostasis, promotes thermogenesis, and modulates the gut microbiota, which collectively resulted in an improved metabolic phenotype. bile acids; bile diversion; obesity; energy expenditure; gut microbiota; gastric bypass; mice

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confidence: 99%

Activation of bile acid signaling improves metabolic phenotypes in high-fat diet-induced obese mice

Pierre

Martinez

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…A potential future probiotic treatment could also involve Akkermansia muciniphila, a bacteria able to reverse high-fat diet induced metabolic disorders in mice [56]**. The association between Akkermansia muciniphila and a healthier metabolic status has been recently validated in human study [57]*.…”

Section: Promotion Of Beneficial Bacteria Growth: Prebiotic Supplemenmentioning

confidence: 99%

The microbiome and its pharmacological targets: therapeutic avenues in cardiometabolic diseases

Neves

Chilloux

Sarafian

et al. 2015

Current Opinion in Pharmacology

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“…9 The findings by Salamon et al 6 with A muciniphila are in contrast to several other studies which have demonstrated that obesity and related metabolic dysfunction are characterized by decreased fecal concentrations of this bacterium. 10 Interestingly, the microbiota composition in T1DM subjects did not differ sig nificantly from that in healthy controls. 6 Some at tention regarding the presented results, however, is needed as authors could not provide data on di etary details and stool consistency, both factors substantially affecting gut microbiota composi tion.…”

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Microbiota and diabetes: an increasingly relevant association

Tilg¹,

Grander²

2018

Polish Archives of Internal Medicine

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333field was opened for further investigations and the term "altered microbiota signature in T2D" was established.In this issue of Polish Archives of Internal Medicine (Pol Arch Intern Med), Salamon et al 6 report on a small study where they investigated fecal microbiome in patients with T1DM, T2DM, and healthy controls. Using 16S ribosomal RNA next generation sequencing, the authors observed that patients with T2DM differed with respect to their microbiome from both T1DM subjects and healthy controls. Patients with T2DM were char acterized by a higher ratio of Firmicutes to Bac teroidetes and demonstrated reduced fecal con centrations of certain Ruminococcaceae, Lachno spiraceae, Clostridiales, Bacteroides, Anaerostipes, and Roseburia, whereas the concentrations of Ruminococcus, Enterobacteriaceae and Proteobacte ria, all rather proinflammatory bacterial strains, were increased. Proteobacteria are considered pro inflammatory and might be able to drive immune responses characterized by increased interferon γ expression. 7 Concentrations of Akkermansia muciniphila, a rather well characterized commensal with mainly antidiabetic and anti inflammatory properties, 8 were increased in T2DM patients in the study by Salomon et al, 6 and the authors pro posed that accompanying metformin treatment might have caused this effect. 9 The findings by Salamon et al 6 with A muciniphila are in contrast to several other studies which have demonstrated that obesity and related metabolic dysfunction are characterized by decreased fecal concentrations of this bacterium. 10 Interestingly, the microbiota composition in T1DM subjects did not differ sig nificantly from that in healthy controls. 6 Some at tention regarding the presented results, however, is needed as authors could not provide data on di etary details and stool consistency, both factors substantially affecting gut microbiota composi tion. Furthermore, the number of analyzed pa tients was rather low (T1DM, n = 22; T2DM, n = 23; controls, n = 23). Despite these shortcomings, The human intestinal tract contains an enor mous number of bacteria, archaea, and virus es. Recent estimates announced that a ratio of 1.3 bacterial cells might exist for every 1 hu man cell. 1 Early studies believed that genes of this microbial world mainly encode functions affecting pathways favoring digestion of com plex carbohydrates or the control of immunity, whereas recent evidence supports that the mi crobiota has major functions in the regulation of metabolic pathways in health and disease. 2 It has been shown in the past years that obese human subjects exhibit a gut microbiome sig nature. 3 Two major studies from the following years showed that such a microbiome signature might also exist in humans with type 2 diabe tes mellitus (T2DM). 4,5 In the first metagenome wide association study, researchers from Chi na demonstrated an intestinal dysbiosis char acterized by a decrease in butyrate producing Roseburia intestinalis and Faecalibacterium prausnitzii. 4 When analyzing potentially associated...

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Akkermansia muciniphilaand improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology

Cited by 1,482 publications

References 65 publications

Activation of bile acid signaling improves metabolic phenotypes in high-fat diet-induced obese mice

Activation of bile acid signaling improves metabolic phenotypes in high-fat diet-induced obese mice

The microbiome and its pharmacological targets: therapeutic avenues in cardiometabolic diseases

Microbiota and diabetes: an increasingly relevant association

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