Abstract：
Type 2 diabetes (T2D), a global health concern, is closely associated with the gut microbiota. Restoration of a balanced microbiota and intestinal homeostasis benefit therapy of T2D. Some special phages may selectively alter the gut microbiota without causing dysbiosis, such as MS2 and P22. However, scarcely systematic analysis of cascading effects triggered by MS2 and P22 phages on the microbiota, as well as interactions between specific gut bacteria and systemic metabolism, seriously inhibit the development of positive interventions of phages. Based on multi-omic analysis, we analyzed the intrinsic correlations among specific microbiota, their bioactive metabolites, and key indicators of T2D. We found that gavage of the MS2-P22 phage cocktail could significantly alter the gut microbiome to attenuate dysbiosis of diabetic C57BL/6 mice caused by high-fat diets (HFDs) and streptozotocin (STZ), by affecting microbial compositions as well as their metabolic pathways and metabolites, especially increasing amounts of short-chain fatty acid-producing (SCFA-producing) bacteria (e.g., Blautia and Romboutsia) and short-chain fatty acids (SCFAs). Correspondingly, a noteworthy reduction in the number of several opportunistic pathogens occurred, e.g., Candidatus Saccharimonas, Aerococcus, Oscillibacter, Desulfovibrio, and Clostridium sensu stricto 1. Synchronously, the levels of proinflammatory cytokines and lipopolysaccharide (LPS) were reduced to recover gut barrier function in T2D mice. These findings might benefit the development of a new dietary intervention for T2D based on phage cocktails. KEY POINTS: • Intestinal barrier integrity of T2D mice is improved by a phage cocktail • Negative relationship between Muribaculaceae and Corynebacterium reshaped gut microbiota • Acetate, propionate, and butyrate decreased the level of proinflammatory factors.
摘要：
2型糖尿病(T2D),全球健康问题，与肠道微生物群密切相关。恢复平衡的微生物群和肠道稳态对T2D有益的治疗。一些特殊的噬菌体可以选择性地改变肠道微生物群，而不会引起菌群失调。如MS2和P22。然而,几乎没有系统分析MS2和P22噬菌体对微生物群的级联效应，以及特定肠道细菌和系统代谢之间的相互作用，严重抑制噬菌体积极干预措施的发展。基于多元分析，我们分析了特定微生物群之间的内在相关性，它们的生物活性代谢物，和T2D的关键指标。我们发现，MS2-P22噬菌体混合物的管饲法可以显着改变肠道微生物组，以减轻由高脂饮食（HFDs）和链脲佐菌素（STZ）引起的糖尿病C57BL/6小鼠的菌群失调。通过影响微生物组成及其代谢途径和代谢产物，特别是增加产生短链脂肪酸(产生SCFA)的细菌(例如，Blautia和Romboutsia）和短链脂肪酸（SCFA）。相应地,几种机会病原体的数量显着减少，例如，CandidatusSacchiimonas,Aerococcus,镰刀菌,Desulfovibrio,和严格的感觉梭菌1.同步,降低T2D小鼠的促炎细胞因子和脂多糖（LPS）水平以恢复肠屏障功能。这些发现可能有利于基于噬菌体鸡尾酒的T2D新饮食干预的发展。关键点：•通过噬菌体鸡尾酒改善了T2D小鼠的肠道屏障完整性•Muribaculaceae和棒状杆菌重塑的肠道微生物群之间的负相关关系•醋酸盐，丙酸盐,丁酸降低促炎因子水平。
