Background & Aims

Epidemiological and animal studies have indicated an inverse correlation between the rising prevalence of obesity and metabolic syndrome and exposure to helminths. Whether helminth-induced immune response contributes to microbiota remodeling in obesity remains unknown. The aim of this study is to explore the immune-regulatory role of helminth in the prevention of HFD-induced obesity through remodeling gut microbiome.

Methods

C57BL/6J WT and STAT6^-/- mice were infected with Heligmosomoides polygyrus and followed by high fat diet (HFD) feeding for 6 weeks. The host immune response, body weight, and fecal microbiota composition were analyzed. We used adoptive transfer of M2 macrophages and microbiota transplantation approaches to determine the impact of these factors on HFD-obesity. We also examined stool microbiota composition and short chain fatty acids (SCFAs) concentration and determined the expression of SCFA-relevant receptors in the recipient mice.

Results

Helminth infection of STAT6^-/- (Th2-deficient) mice and adoptive transfer of helminth-induced alternatively activated (M2) macrophages demonstrated that the helminth-associated Th2 immune response plays an important role in the protection against obesity and induces changes in microbiota composition. Microbiota transplantation showed that helminth-induced, Th2-dependent alterations of the gut microbiota are sufficient to confer protection against obesity. Collectively, these results indicate that helminth infection protects against HFD-induced obesity by Th2-dependent, M2 macrophage-mediated alterations of the intestinal microbiota.

Conclusion

Our findings provide new mechanistic insights into the complex interplay between helminth infection, the immune system and the gut microbiota in a HFD-induced obesity model and holds promise for gut microbiome-targeted immunotherapy in obesity prevention.

中文翻译：

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肠道微生物群的蠕虫诱导和 Th2 依赖性改变可减轻高脂饮食引起的肥胖。

背景与目标

流行病学和动物研究表明，肥胖和代谢综合征的患病率上升与蠕虫接触之间呈负相关。蠕虫诱导的免疫反应是否有助于肥胖中的微生物群重塑仍然未知。本研究的目的是通过重塑肠道微生物组探索蠕虫在预防 HFD 引起的肥胖中的免疫调节作用。

方法

用Heligmosomoides polygyrus感染C57BL/6J WT 和 STAT6 ^-/-小鼠，然后用高脂肪饮食 (HFD) 喂养 6 周。分析了宿主免疫反应、体重和粪便微生物群组成。我们使用 M2 巨噬细胞的过继转移和微生物群移植方法来确定这些因素对 HFD 肥胖的影响。我们还检查了粪便微生物群组成和短链脂肪酸 (SCFA) 浓度，并确定了受体小鼠中 SCFA 相关受体的表达。

结果

STAT6 ^-/- (Th2 缺陷) 小鼠的蠕虫感染和蠕虫诱导的替代激活 (M2) 巨噬细胞的过继转移表明，蠕虫相关的 Th2 免疫反应在预防肥胖和诱导微生物群组成的变化中起重要作用. 微生物群移植表明，蠕虫诱导的、依赖于 Th2 的肠道微生物群改变足以提供对肥胖的保护。总的来说，这些结果表明蠕虫感染通过 Th2 依赖性、M2 巨噬细胞介导的肠道微生物群改变来防止 HFD 诱导的肥胖。

结论

我们的研究结果为 HFD 诱导的肥胖模型中蠕虫感染、免疫系统和肠道微生物群之间的复杂相互作用提供了新的机制见解，并为肠道微生物组靶向免疫疗法在肥胖预防中提供了希望。