Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome

Perry, Rachel J.; Peng, Liang; Barry, Natasha A.; Cline, Gary W.; Zhang, Dongyan; Cardone, Rebecca L.; Petersen, Kitt Falk; Kibbey, Richard G.; Goodman, Andrew L.; Shulman, Gerald I.

doi:10.1038/nature18309

Cited by 1,080 publications

(849 citation statements)

References 24 publications

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“…Infusion of acetate, but not butyrate or propionate, in chowfed rats mimicked increased GSIS as observed in HFD-fed rats suggesting that circulating acetate levels drive increased GSIS [4]. In line with this, FMT from HFD-fed rats to chow-fed controls increased acetate turnover and GSIS in the recipient rat.…”

Section: Role Of Specific Bacterial Metabolites In Regulation Of Hostsupporting

confidence: 63%

“…Perry and co-workers recently showed that the SCFA acetate acts on parasympathetic activity to increase food intake and promote glucose-stimulated insulin secretion (GSIS) in a rat model [4]. Interestingly, acetate turnover, but not that of butyrate or propionate, was found to be increased in the colon, caecum and brain of rats fed an HFD compared with chow-fed rats.…”

Section: Role Of Specific Bacterial Metabolites In Regulation Of Hostmentioning

confidence: 96%

“…This commentary discusses two recent rodent studies on the potential importance of the intestinal microbiota in metabolic disease. Ussar and co-workers [3] studied the complex interaction between environmental and genetic factors in microbiota-related metabolic disease development in mice, while Perry and co-workers [4] investigated a potential mechanism underlying microbiota-driven disease development using a rat model.…”

Section: Bbbmentioning

confidence: 99%

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Emerging role of intestinal microbiota and microbial metabolites in metabolic control

Herrema

IJzerman²,

Nieuwdorp

2016

Diabetologia

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The role of the intestinal microbiota and microbial metabolites in the maintenance of host health and development of metabolic disease has gained significant attention over the past decade. Mechanistic insight revealing causality, however, is scarce. Work by Ussar and co-workers demonstrates that a complex interaction between microbiota, host genetics and environmental factors is involved in metabolic disease development in mice. In addition, Perry and coworkers show that the microbial metabolite acetate augments insulin resistance in rats. These studies underscore an important role of the microbiota in the development of obesity and symptoms of type 2 diabetes in rodents. If causality can be demonstrated in humans, development of novel diagnostic and therapeutic tools that target the gut microbiota will have high potential.Keywords Gut microbiota . Insulin resistance . Obesity . Short-chain fatty acids . Type 2 diabetes Abbreviations BBB Blood-brain barrier FMT Faecal microbiota transfer GSIS Glucose-stimulated insulin secretion HFD High-fat diet ICV Intracerebroventricular SCFA Short-chain fatty acidThe symbiotic relationship with our intestinal microbiota is exemplified by a broad range of beneficial effects for the host metabolism, including digestion of complex carbohydrates and maturation of the immune response. In addition, the intestinal microbiota serves an endocrine role by producing a vast amount of metabolites with the potential to modulate host metabolism [1]. The intestinal microbiota has, as such, also been implicated in the development of obesity and type 2 diabetes in human and rodent models [2]. This adds another layer of complexity to studying the origin of these multifactorial metabolic pathologies that arise from a complicated interplay between genetic risk factors and external factors, including dietary intake and physical activity. This commentary discusses two recent rodent studies on the potential importance of the intestinal microbiota in metabolic disease. Ussar and co-workers [3] studied the complex interaction between environmental and genetic factors in microbiota-related metabolic disease development in mice, while Perry and co-workers [4] investigated a potential mechanism underlying microbiota-driven disease development using a rat model.Colonisation of the gastrointestinal tract starts as early as in utero [5], and a core microbiome composed mainly of Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria and Verrucomicrobia is established around the third year of life. Extrinsic factors, including host genetic makeup [6], cohousing/family members [7], oral antibiotic use early in life [8] and diet [9] are dominating factors in shaping the intestinal microbiota. Whether these early life events are determinants of microbiota-related disease in later life remains to be

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Section: Role Of Specific Bacterial Metabolites In Regulation Of Hostsupporting

confidence: 63%

Section: Role Of Specific Bacterial Metabolites In Regulation Of Hostmentioning

confidence: 96%

Section: Bbbmentioning

confidence: 99%

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Emerging role of intestinal microbiota and microbial metabolites in metabolic control

Herrema

IJzerman²,

Nieuwdorp

2016

Diabetologia

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“…Specific microbiome profiles are associated with increased glucose intolerance [30]. Alterations in gut microbiota can influence the gut metabolome in a manner that affects the intestinal output of butyrate [24] and acetate [31]. These are important examples of gut-derived metabolites that can influence host insulin resistance, and thus glycaemic control.…”

Section: Metformin and Gut Microbiotamentioning

confidence: 99%

The effects of metformin on gut microbiota and the immune system as research frontiers

Pollak

2017

Diabetologia

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Recent studies have revealed that metformin influences gut microbiota and the immune system although neither is a classic target of the drug. This research has revealed complexity not previously appreciated, and opened new research directions. The extent to which immunomodulatory effects and actions on the microbiota are related to each other and account for effects on host energy metabolism remains to be determined. These sites of action may be relevant not only to the efficacy of metformin for its established use in type 2 diabetes, but also to proposed novel indications in oncology and other diseases.

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“…In normal mice with normal gut microbiota, inactive AMPK is associated with decreased FA oxidation in skeletal muscle (36). In addition, gut satiety hormones are affected by the gut microbiome through the gut-brain axis (65). Therefore, the gut microbiome influences energy intake in addition to energy expenditure.…”

Section: Introductionmentioning

confidence: 99%

Nonalcoholic Fatty Liver Disease, the Gut Microbiome, and Diet

Mokhtari

Gibson

Hekmatdoost

2017

Advances in Nutrition

138

100

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Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in the world, yet the pathogenesis of the disease is not well elucidated. Due to the close anatomic and functional association between the intestinal lumen and the liver through the portal system, it is speculated that the gut microbiome may play a pivotal role in the pathogenesis of NAFLD. Furthermore, diet, which can modulate the gut microbiome and several metabolic pathways involved in NAFLD development, shows a potential tripartite relation between the gut, diet, and the liver. In this review, we summarize the current evidence that supports the association between NAFLD, the gut microbiome, and the role of diet. Adv Nutr 2017;8:240-52.

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Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome

Cited by 1,080 publications

References 24 publications

Emerging role of intestinal microbiota and microbial metabolites in metabolic control

Emerging role of intestinal microbiota and microbial metabolites in metabolic control

The effects of metformin on gut microbiota and the immune system as research frontiers

Nonalcoholic Fatty Liver Disease, the Gut Microbiome, and Diet

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