Objective: Emerging evidence indicates that Akkermansia muciniphila (A. muciniphila or AKK) regulates host glucose metabolism through multiple pathways. In this study, we examined the therapeutic effects of A. muciniphila on chronic sleep deprivation (CSD)-induced glucose dysregulation and the underlying mechanisms. Methods: A modified multiplatform water environment method was used to generate a mouse model of CSD. The mice were divided into three groups: the control (CON) group (ad libitum sleep), the CSD group (subjected to sleep deprivation), and the CSD+AKK group (CSD mice were supplemented with A. muciniphila at 3 × 10⁸ CFU per mouse, three times per week). After an 8-week intervention, glucose metabolism was assessed. Serum concentrations of lipopolysaccharide (LPS), interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) were measured. The mRNA expression and protein expression of mucin 2 (MUC2) and zonula occludens-1 (ZO-1) in the colon tissue were analyzed. Goblet cells in colon tissues were quantified using Alcian Blue–Periodic Acid-Schiff (AB–PAS) staining. Additionally, changes in gut microbiome diversity and composition among groups were compared. Results: CSD induced significant glucose intolerance and insulin resistance, evidenced by increased area under the curve (AUC) of the oral glucose tolerance test (OGTT), homeostatic model assessment of insulin resistance (HOMA-IR), and fasting insulin levels compared to the CON group (all p < 0.05). This was accompanied by a marked impairment of the colonic mucosal barrier, characterized by a profound loss of goblet cells and downregulation of key barrier components, MUC2 and ZO-1, at both the mRNA and protein levels (all p < 0.05). Intervention with A. muciniphila significantly ameliorated CSD-induced glucose intolerance, insulin resistance and colonic barrier damage. Furthermore, CSD elevated serum levels of LPS, IL-6, TNF-α, and IL-1β (all p < 0.05), which were effectively mitigated by A. muciniphila intervention. 16S rDNA sequencing confirmed the successful colonization of A. muciniphila, as its absolute abundance was significantly greater in the CSD+AKK group than in the CSD group. In addition, A. muciniphila intervention affected the abundance of Burkholderiales bacterium, Lactococcus garvieae, and other bacterial strains in the intestine. Conclusion: A. muciniphila supplementation effectively ameliorated CSD-induced glucose intolerance, reduced the serum levels of LPS and proinflammatory cytokines (IL-6, TNF-α, and IL-1β), and restored intestinal barrier integrity by upregulating MUC2 and ZO-1 expression in colon tissues.
Wang et al. (Wed,) studied this question.