Diverse effects of different Akkermansia muciniphila genotypes on Brown adipose tissue inflammation and whitening in a high-fat-diet murine model.

BACKGROUND: The purpose of this study was to investigate the differences in the metabolic protective effects of Akkermansia muciniphila (A.muciniphila) genotypes on high-fat diet mice and explore possible mechanisms. METHODS: Male C57BL/6 mice were randomly divided into 6 groups, including high-fat diet (HFD)+ A. muciniphila I/II/PBS group, normal control diet (NCD)+ A. muciniphila I/II/PBS group, respectively. Dietary intervention and A. muciniphila gavage were performed simultaneously. Blood glucose and lipid metabolism, brown adipose morphology and activities, and intestinal barrier function were examined after the mice were sacrificed. RESULTS: A.muciniphila gavage improved the impaired glucose tolerance, hyperlipidemia and liver steatosis in HFD mice, and that A. muciniphila II (Amuc_GP25) was not as effective as A. muciniphila I (Amuc_GP01). This phenomenon might be because Amuc_GP01 intervention significantly inhibited brown adipose tissue whitening and inflammation induced by HFD, by repairing the intestinal barrier and relieving endotoxemia. Amuc_GP25 did not display the same results as Amuc_GP01 in HFD mice but had stronger effects in the NCD mice. CONCLUSIONS: This study reveals the distinct functions of different A. muciniphila genotypes on diet-induced obesity, suggesting that different A. muciniphila genotypes may affect pathological conditions differently through distinct action pathways.

A potential probiotic bacterium for antipsychotic-induced metabolic syndrome: mechanisms underpinning how Akkermansia muciniphila subtype improves olanzapine-induced glucose homeostasis in mice.

BACKGROUND: Olanzapine (OLZ) is one of the most effective atypical antipsychotics but is associated with severe metabolic side effects, in which the gut microbiota plays an important role. Akkermansia muciniphila (A. muciniphila; Akk), a Gram-negative anaerobic bacterium in the intestine, can potentially improve metabolic syndrome. OBJECTIVE: This study investigated the effect and underlying mechanisms of an A. muciniphila subtype (A. muciniphilasub; Akksub) on OLZ-induced metabolic dysfunction in lean and obese mice. METHODS: C57BL/6 female mice were fed a high-fat diet to induce obesity or normal chow for 8 weeks before OLZ treatment for 16 weeks. During the treatment period, mice in each group were orally administrated A. muciniphilasub. Weight gain, glucose and lipid metabolism, and inflammation were evaluated. RESULTS: A. muciniphilasub decreased OLZ-related weight gain only at week 16 in lean mice and significantly alleviated OLZ-induced hyperglycemia irrespective of diet. This was accompanied by reduced levels of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK)-key enzymes in hepatic gluconeogenesis-and OLZ-associated insulin resistance. Moreover, OLZ-induced increases in serum interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels were improved by A. muciniphilasub in both obese and lean mice. OLZ did not increase serum lipid levels or hepatic fat accumulation. CONCLUSIONS: A. muciniphilasub improves OLZ-related hyperglycemia via regulation of G6Pase and PEPCK levels and insulin resistance. Moreover, A. muciniphilasub alleviates systemic inflammation caused by OLZ. A. muciniphilasub is a promising probiotic treatment for OLZ-induced metabolic dysfunction.

Protective effects of Akkermansia muciniphila on cognitive deficits and amyloid pathology in a mouse model of Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) is a global health problem without effective methods to alleviate the disease progression. Amyloid ß-protein (Aß) is widely accepted as a key biomarker for AD. Metabolic syndromes, including obesity and insulin resistance, are key high risk factors for AD. Akkermansia muciniphila (Akk), the only representative human gut microbe in the genus Verrucomicrobia, can prevent the weight gain caused by a high-fat diet, repair the damaged integrity of the intestinal epithelium barrier, reduce endotoxin levels in blood and improve insulin resistance. The aim of this study is to explore the impact of Akk administration in AD model mice in different diets. METHODS: APP/PS1 mice were fed either a normal chow diet or a high-fat diet and were treated with Akk by gavage each day for 6 months. The impacts of Akk on glucose metabolism, intestinal barrier and lipid metabolism in the mouse model of AD were determined. Changes in brain pathology and neuroethology were also analyzed. RESULTS: Akk effectively reduced the fasting blood glucose and serum diamine oxidase levels, and alleviated the reduction of colonic mucus cells in APP/PS1 mice. After treatment with Akk, the APP/PS1 mice showed obviously reduced blood lipid levels, improved hepatic steatosis and scapular brown fat whitening. Moreover, Akk promoted the reduction of Aß 40-42 levels in the cerebral cortex of APP/PS1 mice, shortened the study time and improved the completion rate in Y-maze tests. CONCLUSION: Akk effectively improved glucose tolerance, intestine barrier dysfunction and dyslipidemia in AD model mice. Our study results suggested that Akk could delay the pathological changes in the brain and relieve impairment of spatial learning and memory in AD model mice, which provides a new strategy for prevention and treatment of AD.