The incidence of metabolic syndrome continues to rise globally. In mice, intravenous administration of interleukin-22 (IL-22) ameliorates various disease phenotypes associated with diet-induced metabolic syndrome. In patients, oral treatment is favored over intravenous treatment, but methodologies to deliver IL-22 via the oral route are nonexistent. The goal of this study was to assess to what extent engineered Lactobacillus reuteri secreting IL-22 could ameliorate nonalcoholic fatty liver disease. We used a mouse model of diet-induced obesity and assessed various markers of metabolic syndrome following treatment with L. reuteri and a recombinant derivative. Mice that received an 8-week treatment of wild-type probiotic gained less weight and had a smaller fat pad than the control group, but these phenotypes were not further enhanced by recombinant L. reuteri. However, L. reuteri secreting IL-22 significantly reduced liver weight and triglycerides at levels that exceeded those of the probiotic wild-type treatment group. Our findings are interesting in light of the observed phenotypes associated with reduced nonalcoholic liver disease, in humans the most prevalent chronic liver disease, following treatment of a next-generation probiotic that is administered orally. Once biological and environmental containment strategies are in place, therapeutic applications of recombinant Lactobacillus reuteri are on the horizon.

中文翻译：

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工程化罗伊氏乳杆菌分泌重组白细胞介素 22 可减少饮食引起的肥胖小鼠模型中的脂肪肝疾病。


全球代谢综合征的发病率持续上升。在小鼠中，静脉注射白细胞介素 22 (IL-22) 可改善与饮食诱导的代谢综合征相关的各种疾病表型。对于患者来说，口服治疗优于静脉注射治疗，但通过口服途径递送 IL-22 的方法尚不存在。本研究的目的是评估分泌 IL-22 的工程化罗伊氏乳杆菌能在多大程度上改善非酒精性脂肪肝。我们使用了饮食诱导肥胖的小鼠模型，并评估了用罗伊氏乳杆菌和重组衍生物治疗后代谢综合征的各种标志物。与对照组相比，接受野生型益生菌治疗 8 周的小鼠体重增加较少，脂肪垫也较小，但重组罗伊氏乳杆菌并未进一步增强这些表型。然而，分泌 IL-22的罗伊氏乳杆菌显着降低了肝脏重量和甘油三酯，其水平超过了益生菌野生型治疗组。我们的研究结果很有趣，因为在口服下一代益生菌治疗后，观察到与非酒精性肝病（人类最常见的慢性肝病）减少相关的表型。一旦生物和环境遏制策略到位，重组罗伊氏乳杆菌的治疗应用就即将出现。