BackgroundObesity, a global epidemic, disrupts bone metabolism via gut microbiota dysbiosis, and probiotic/postbiotic supplementation emerges as a promising intervention. Akkermansia muciniphila (Akk), a next-generation probiotic, exerts metabolic benefits in obesity, yet its effects on bone homeostasis—especially in pasteurized form (pAkk)—and underlying mechanisms remain unclear.MethodsHigh-fat diet (HFD)-induced obese mice were used to establish bone loss models, with fecal microbiota transplantation to verify gut microbiota’s role.
Mice were gavaged with live Akk, pAkk, or control for 4 weeks. Bone microarchitecture was assessed via micro-computed tomography (μCT), and bone formation/resorption were detected by histomorphometry, ELISA, and TRAP staining.
Flow cytometry, immunofluorescence, and qRT-PCR analyzed regulatory T (Treg) cell differentiation. RNA sequencing identified key genes, and Nr4a1 knockout mice validated the mechanism.
Cell coculture confirmed pAkk-induced Tregs’ inhibitory effect on osteoclastogenesis.ResultsObesity-related gut microbiota induced trabecular bone loss, with reduced intestinal Akk abundance. pAkk (but not live Akk) rescued HFD-induced bone loss, increased bone formation marker (P1NP), decreased resorption marker (β-CTX), and inhibited osteoclast differentiation.
pAkk promoted CD4+CD25+Foxp3+ Treg differentiation in the intestine and spleen via CD103+ dendritic cells, and these Tregs suppressed osteoclastogenesis.
Frontiers in Immunology published a clinical update in Infectious Disease on 22 May 2026.
The item focuses on Pasteurized Akkermansia muciniphila alleviates high-fat diet-induced bone loss via Nr4a1-dependent Treg differentiation.
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