Department of Food Science, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
mSphere. 2020 Jun 24;5(3):e00183-20. doi: 10.1128/mSphere.00183-20.
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 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 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 However, 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 are on the horizon. In humans, nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease due to the increased prevalence of obesity. While treatment of NAFLD is often geared toward lifestyle changes, such as diet and exercise, the use of dietary supplements such as probiotics is underinvestigated. Here, we report that probiotic reduces fatty liver in a mouse model of diet-induced obesity. This phenotype was further enhanced upon delivery of recombinant interleukin-22 by engineered These observations pave the road to a better understanding of probiotic mechanisms driving the reduction of diet-induced steatosis and to development of next-generation probiotics for use in the clinic. Ultimately, these studies may lead to rational selection of (engineered) probiotics to ameliorate fatty liver disease.
代谢综合征的发病率在全球范围内持续上升。在小鼠中，静脉内给予白细胞介素 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。在患者中，口服治疗优于静脉内治疗，但通过口服途径给予 IL-22 的方法尚不存在。本研究的目的是评估工程化分泌的 IL-22 在多大程度上可以改善非酒精性脂肪性肝病。我们使用了饮食诱导肥胖的小鼠模型，并在接受 和重组衍生物治疗后评估了代谢综合征的各种标志物。接受野生型益生菌 8 周治疗的小鼠体重增加较少，脂肪垫较小，但这些表型并未因重组 而进一步增强。然而，分泌 IL-22 的 显著降低了肝重和甘油三酯，其水平超过了益生菌野生型治疗组。鉴于观察到的与非酒精性肝病相关的表型，我们的发现很有趣，在非酒精性肝病是最常见的慢性肝病，在口服给予新一代益生菌治疗后，观察到了这种表型。一旦制定了生物和环境遏制策略，重组 的治疗应用就有了前景。在人类中，非酒精性脂肪性肝病（NAFLD）是最常见的肝脏疾病，因为肥胖的患病率增加。虽然 NAFLD 的治疗通常侧重于生活方式的改变，如饮食和运动，但对益生菌等膳食补充剂的使用研究不足。在这里，我们报告益生菌 通过饮食诱导肥胖的小鼠模型减少脂肪肝。在通过工程化 递送重组白细胞介素 22 后，这种表型进一步增强。这些观察结果为更好地理解益生菌减少饮食诱导的脂肪变性的机制铺平了道路，并为开发用于临床的下一代益生菌奠定了基础。最终，这些研究可能导致合理选择（工程化）益生菌来改善脂肪肝疾病。
