Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Canada.
Department of Laboratory Medicine and Pathology, Stollery Children's Hospital, University of Alberta, Edmonton, Alberta, Canada.
Appl Environ Microbiol. 2023 Mar 29;89(3):e0162822. doi: 10.1128/aem.01628-22. Epub 2023 Feb 21.
Changes in the gut microbiota have been linked to metabolic endotoxemia as a contributing mechanism in the development of obesity and type 2 diabetes. Although identifying specific microbial taxa associated with obesity and type 2 diabetes remains difficult, certain bacteria may play an important role in initiating metabolic inflammation during disease development. The enrichment of the family , largely represented by Escherichia coli, induced by a high-fat diet (HFD) has been correlated with impaired glucose homeostasis; however, whether the enrichment of in a complex gut microbial community in response to an HFD contributes to metabolic disease has not been established. To investigate whether the expansion of amplifies HFD-induced metabolic disease, a tractable mouse model with the presence or absence of a commensal E. coli strain was established. With an HFD treatment, but not a standard-chow diet, the presence of E. coli significantly increased body weight and adiposity and induced impaired glucose tolerance. In addition, E. coli colonization led to increased inflammation in liver and adipose and intestinal tissue under an HFD regimen. With a modest effect on gut microbial composition, E. coli colonization resulted in significant changes in the predicted functional potential of microbial communities. The results demonstrated the role of commensal E. coli in glucose homeostasis and energy metabolism in response to an HFD, indicating contributions of commensal bacteria to the pathogenesis of obesity and type 2 diabetes. The findings of this research identified a targetable subset of the microbiota in the treatment of people with metabolic inflammation. Although identifying specific microbial taxa associated with obesity and type 2 diabetes remains difficult, certain bacteria may play an important role in initiating metabolic inflammation during disease development. Here, we used a mouse model distinguishable by the presence or absence of a commensal Escherichia coli strain in combination with a high-fat diet challenge to investigate the impact of E. coli on host metabolic outcomes. This is the first study to show that the addition of a single bacterial species to an animal already colonized with a complex microbial community can increase severity of metabolic outcomes. This study is of interest to a wide group of researchers because it provides compelling evidence to target the gut microbiota for therapeutic purposes by which personalized medicines can be made for treating metabolic inflammation. The study also provides an explanation for variability in studies investigating host metabolic outcomes and immune response to diet interventions.
肠道微生物群的变化与代谢性内毒素血症有关，这是肥胖和 2 型糖尿病发展的一个致病机制。虽然确定与肥胖和 2 型糖尿病相关的特定微生物类群仍然具有挑战性，但某些细菌可能在疾病发展过程中引发代谢性炎症中发挥重要作用。高脂肪饮食（HFD）诱导的家族丰度增加，主要由大肠杆菌代表，与葡萄糖稳态受损有关；然而，在 HFD 作用下，复杂肠道微生物群落中是否存在丰度增加导致代谢疾病尚不清楚。为了研究丰度增加是否会放大 HFD 诱导的代谢性疾病，建立了一种具有共生大肠杆菌存在或不存在的可处理的小鼠模型。用 HFD 处理，但不用标准饲料喂养时，大肠杆菌的存在显著增加了体重和肥胖度，并导致葡萄糖耐量受损。此外，在 HFD 方案下，大肠杆菌定植导致肝脏、脂肪组织和肠道组织的炎症增加。尽管对肠道微生物组成的影响较小，但大肠杆菌定植导致微生物群落的预测功能潜力发生显著变化。结果表明，共生大肠杆菌在 HFD 作用下对葡萄糖稳态和能量代谢起作用，表明共生细菌对肥胖和 2 型糖尿病发病机制的贡献。该研究的结果确定了治疗代谢性炎症人群中可靶向的微生物亚群。虽然确定与肥胖和 2 型糖尿病相关的特定微生物类群仍然具有挑战性，但某些细菌可能在疾病发展过程中引发代谢性炎症中发挥重要作用。在这里，我们使用了一种可区分是否存在共生大肠杆菌菌株的小鼠模型，结合高脂肪饮食挑战，研究了大肠杆菌对宿主代谢结果的影响。这是第一项表明将单一细菌物种添加到已经定植复杂微生物群落的动物中会增加代谢结果严重程度的研究。这项研究引起了广泛研究人员的兴趣，因为它提供了令人信服的证据，表明可以通过靶向肠道微生物群来进行治疗，从而可以为治疗代谢性炎症制定个性化药物。该研究还解释了研究宿主代谢结果和对饮食干预的免疫反应的变异性。
