An Akkermansia muciniphila subtype alleviates high-fat diet-induced metabolic disorders and inhibits the neurodegenerative process in mice

Wu, Feng; Guo, Xianfeng; Zhang, Min; Ou, Zihao; Wu, Dan; Deng, Lulu; Lu, Ziwen; Zhang, Jiachun; Deng, Guihua; Chen, Shengqiang; Li, Shenghui; Yi, Jiangfeng; Peng, Yongzheng

doi:10.1016/j.anaerobe.2019.102138

Cited by 64 publications

(63 citation statements)

References 34 publications

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“…As shown in , A. muciniphila induced a marked increase of Actinobacteria, which was consistent with a previous study ( Wu et al, 2020 ). In addition, A. muciniphila colonization reduced the abundance of γ-Proteobacteria and led to an increasing trend of Bacteroidetes.…”

Section: Resultssupporting

confidence: 93%

Akkermansia muciniphila promotes type H vessel formation and bone fracture healing by reducing gut permeability and inflammation

Liu

Tao

Luo

et al. 2020

Disease Models &Amp; Mechanisms

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Improving revascularization is one of the major measures in fracture treatment. Moderate local inflammation triggers angiogenesis, whereas systemic inflammation hampers angiogenesis. Previous studies showed that Akkermansia muciniphila (A. muc), a gut probiotic, ameliorates systemic inflammation by tightening intestinal barrier. In this study, fractured mice intragastrically administrated with A. muc were found to display better fracture healing than mice treated with vehicle. Notably, more preosteclasts positive for platelet-derived growth factor-BB (PDGF-BB) were induced by A. muc at 2 weeks post fracture, coinciding with increased formation of type H vessels, a specific vessel subtype that couples angiogenesis and osteogenesis and can be stimulated by PDGF-BB. Moreover, A. muc treatment significantly reduced gut permeability and inflammation at early stage. Dextran Sulfate Sodium (DSS) was used to disrupt the gut barrier to determine the role of gut barrier in fracture healing and whether A. muc still can stimulate bone fracture healing. As expected, A. muc evidently improved gut barrier, reduced inflammation, and restored the impaired bone healing and angiogenesis in DSS-treated mice. Our results suggest that A. muc reduces intestinal permeability and alleviates inflammation, which probably induces more PDGF-BB positive preosteoclasts and type H vessel formation in callus, thereby promoting fracture healing. This study provides the evidences about the involvement of type H vessels in fracture healing and suggests the potential of A. muc as a promising strategy for bone healing.

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Section: Resultssupporting

confidence: 93%

Akkermansia muciniphila promotes type H vessel formation and bone fracture healing by reducing gut permeability and inflammation

Liu

Tao

Luo

et al. 2020

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

show abstract

“…In addition, the colonic mRNA level of IL-10, a potent anti-inflammatory cytokine that plays a crucial role in preventing inflammatory and autoimmune pathologies [ 65 ], was significantly lower in the HFD group than in the normal group. Previous studies reported that A. muciniphila could elevate the levels of anti-inflammatory cytokines [ 66 ] and reduce the pro-inflammatory conditions to improve the systemic inflammation caused by HFD in mice [ 67 ]. Consistent with these findings, these results showed that treatment of the HFD group with all three A. muciniphila strains selected increased the colonic gene expression of IL-10 significantly and reduced the colonic mRNA levels of TNF-α, MCP-1 and TLR2.…”

Section: Discussionmentioning

confidence: 99%

Beneficial Effects of Newly Isolated Akkermansia muciniphila Strains from the Human Gut on Obesity and Metabolic Dysregulation

et al. 2020

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The identification of new probiotics with anti-obesity properties has attracted considerable interest. In the present study, the anti-obesity activities of Akkermansia muciniphila (A. muciniphila) strains isolated from human stool samples and their relationship with the gut microbiota were evaluated using a high fat-diet (HFD)-fed mice model. Three strains of A. muciniphila were chosen from 27 isolates selected based on their anti-lipogenic activity in 3T3-L1 cells. The anti-lipogenic, anti-adipogenic and anti-obesity properties of these three strains were evaluated further in HFD-induced obese mice. The animals were administered these strains six times per week for 12 weeks. The treatment improved the HFD-induced metabolic disorders in mice in terms of the prevention of body weight gain, caloric intake and reduction in the weights of the major adipose tissues and total fat. In addition, it improved glucose homeostasis and insulin sensitivity. These effects were also associated with the inhibition of low-grade intestinal inflammation and restoration of damaged gut integrity, prevention of liver steatosis and improvement of hepatic function. These results revealed a difference in the distribution pattern of the gut microbial communities between groups. Therefore, the gut microbial population modulation, at least in part, might contribute to the beneficial impact of the selected A. muciniphila strains against metabolic disorders.

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“…The administration of A. muciniphila has been shown to restore intestinal mucus-layer thickness, maintain bacterial homeostasis, and improve high-fat diet-induced metabolic disorders in obese mice by decreasing weight gain, insulin resistance, serum triglycerides, and hepatic inflammation [ 12 , 48 , 49 ]. These anti-obesity effects are potentially due to an increase in energy expenditure as well as fecal energy excretion, which has been associated with a higher intestinal epithelial cell turnover and a reduction in carbohydrate absorption [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Targeting the Intestinal Microbiota to Prevent Type 2 Diabetes and Enhance the Effect of Metformin on Glycaemia: A Randomised Controlled Pilot Study

et al. 2020

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Early treatment may prevent or delay the onset of type 2 diabetes mellitus (T2DM) in individuals who are at high risk. Lifestyle interventions and the hypoglycemic drug metformin have been shown to reduce T2DM incidence. The effectiveness of such interventions may be enhanced by targeting environmental factors such as the intestinal microbiota, which has been proven to predict the response to lifestyle interventions and play a part in mediating the glucose-lowering effects of metformin. Shifts in the intestinal microbiota “towards a more balanced state” may promote glucose homeostasis by regulating short-chain fatty acids’ production. This study aimed to investigate the safety and effect of a multi-strain probiotic on glycemic, inflammatory, and permeability markers in adults with prediabetes and early T2DM and to assess whether the probiotic can enhance metformin’s effect on glycaemia. A randomised controlled pilot study was conducted in 60 adults with a BMI ≥ 25 kg/m2 and with prediabetes or T2DM (within the previous 12 months). The participants were randomised to a multi-strain probiotic (L. plantarum, L. bulgaricus, L. gasseri, B. breve, B. animalis sbsp. lactis, B. bifidum, S. thermophilus, and S. boulardii) or placebo for 12 weeks. Analyses of the primary outcome (fasting plasma glucose) and secondary outcomes, including, but not limited to, circulating lipopolysaccharide, zonulin, and short chain fatty acids and a metagenomic analysis of the fecal microbiome were performed at baseline and 12 weeks post-intervention. The results showed no significant differences in the primary and secondary outcome measures between the probiotic and placebo group. An analysis of a subgroup of participants taking metformin showed a decrease in fasting plasma glucose, HbA1c, insulin resistance, and zonulin; an increase in plasma butyrate concentrations; and an enrichment of microbial butyrate-producing pathways in the probiotic group but not in the placebo group. Probiotics may act as an adjunctive to metformin by increasing the production of butyrate, which may consequently enhance glucose management.

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An Akkermansia muciniphila subtype alleviates high-fat diet-induced metabolic disorders and inhibits the neurodegenerative process in mice

Cited by 64 publications

References 34 publications

Akkermansia muciniphila promotes type H vessel formation and bone fracture healing by reducing gut permeability and inflammation

Akkermansia muciniphila promotes type H vessel formation and bone fracture healing by reducing gut permeability and inflammation

Beneficial Effects of Newly Isolated Akkermansia muciniphila Strains from the Human Gut on Obesity and Metabolic Dysregulation

Targeting the Intestinal Microbiota to Prevent Type 2 Diabetes and Enhance the Effect of Metformin on Glycaemia: A Randomised Controlled Pilot Study

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