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<p>Obesity pathogenesis is closely linked to gut microbiota dysbiosis. <i>Akkermansia muciniphila</i> (<i>A. muciniphila</i>) has emerged as a promising next-generation probiotic candidate due to its metabolic benefits. In this study, we systematically evaluated the therapeutic efficacy of pasteurized <i>A. muciniphila</i> AKK PROBIO (P-AKK PROBIO) in high-fat diet (HFD)-induced obese C57BL/6J mice. The results revealed that P-AKK PROBIO administration significantly ameliorated hepatic steatosis and reduced body weight and body fat percentage by 15.24% and 28.82% over four weeks, respectively. The intervention also improved serum lipid profiles by reducing total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), while increasing high-density lipoprotein cholesterol (HDL-C). Furthermore, P-AKK PROBIO attenuated TNF-α-mediated inflammatory responses. Mechanistically, P-AKK PROBIO enhanced intestinal barrier integrity through upregulation of tight junction proteins (ZO-1 and Occludin) and restored gut microbial homeostasis, as indicated by a decreased Firmicutes/Bacteroidetes ratio. Notably, the treatment enriched beneficial bacterial taxa (<i>Oscillospiraceae</i> and <i>Roseburia</i>) and increased short-chain fatty acids (SCFAs) production, particularly propionate, acetate, and butyrate. These microbial alterations correlated with elevated GLP-1 levels in both hypothalamic and ileal tissues, suggesting a dual mechanism involving GLP-1-dependent appetite regulation and lipid metabolism modulation. Furthermore, P-AKK PROBIO probably regulated key metabolic pathways by upregulating AMPK/PPAR-α signaling while downregulating PPAR-γ cascades. Collectively, these findings provide compelling evidence supporting the potential development of pasteurized <i>A. muciniphila</i> formulations for the management of metabolic disorders.</p> Graphical Abstract <p></p>

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Pasteurized Akkermansia muciniphila AKK PROBIO Attenuates Obesity Through Gut Microbiota-SCFA-GLP-1 Axis and Potential Involvement of AMPK/PPAR-α Pathway

  • 期刊论文

  • 发表日期：

    2025年10月22日

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  • Liu Yang,
  • Yutian Huang,
  • Mengling Chen,
  • Xin Ma,
  • Xueping Yu,
  • Dayong Ren,
  • Yue Leng

摘要

Obesity pathogenesis is closely linked to gut microbiota dysbiosis. Akkermansia muciniphila (A. muciniphila) has emerged as a promising next-generation probiotic candidate due to its metabolic benefits. In this study, we systematically evaluated the therapeutic efficacy of pasteurized A. muciniphila AKK PROBIO (P-AKK PROBIO) in high-fat diet (HFD)-induced obese C57BL/6J mice. The results revealed that P-AKK PROBIO administration significantly ameliorated hepatic steatosis and reduced body weight and body fat percentage by 15.24% and 28.82% over four weeks, respectively. The intervention also improved serum lipid profiles by reducing total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), while increasing high-density lipoprotein cholesterol (HDL-C). Furthermore, P-AKK PROBIO attenuated TNF-α-mediated inflammatory responses. Mechanistically, P-AKK PROBIO enhanced intestinal barrier integrity through upregulation of tight junction proteins (ZO-1 and Occludin) and restored gut microbial homeostasis, as indicated by a decreased Firmicutes/Bacteroidetes ratio. Notably, the treatment enriched beneficial bacterial taxa (Oscillospiraceae and Roseburia) and increased short-chain fatty acids (SCFAs) production, particularly propionate, acetate, and butyrate. These microbial alterations correlated with elevated GLP-1 levels in both hypothalamic and ileal tissues, suggesting a dual mechanism involving GLP-1-dependent appetite regulation and lipid metabolism modulation. Furthermore, P-AKK PROBIO probably regulated key metabolic pathways by upregulating AMPK/PPAR-α signaling while downregulating PPAR-γ cascades. Collectively, these findings provide compelling evidence supporting the potential development of pasteurized A. muciniphila formulations for the management of metabolic disorders.

Graphical Abstract