来自瘦捐赠者的微生物群移植可防止高脂饮食喂养的肥胖大鼠体重过度增加,并恢复肠-脑迷走神经信号传导。

Transfer with microbiota from lean donors prevents excessive weight gain and restores gut-brain vagal signaling in obese rats maintained on a high fat diet.

作者信息

Minaya Dulce M, Kim Jiyoung S, Kirkland Rebecca, Allen Jillian, Cullinan Sitara, Maclang Neil, de Lartigue Guillaume, de La Serre Claire B

机构信息

Department of Nutritional Science, University of Georgia, Athens, GA.

Emory University School of Medicine, Atlanta, GA.

出版信息

Res Sq. 2024 May 31:rs.3.rs-4438240. doi: 10.21203/rs.3.rs-4438240/v1.

Abstract

BACKGROUND

The collection of microorganisms, mainly bacteria, which live in the gastrointestinal (GI) tract are collectible known as the gut microbiota. GI bacteria play an active role in regulation of the host's immune system and metabolism, as well as certain pathophysiological processes. Diet is the main factor modulating GI microbiota composition and recent studies have shown that high fat (HF) diets induce detrimental changes, known as dysbiosis, in the GI bacterial makeup. HF diet induced microbiota dysbiosis has been associated with structural and functional changes in gut-brain vagally mediated signaling system, associated with overeating and obesity. Although HF-driven changes in microbiota composition are sufficient to alter vagal signaling, it is unknown if restoring normal microbiota in obesity can improve gut-brain signaling and metabolic outcomes. In this study, we evaluated the effect of lean gut microbiota transfer in obese, vagally compromised, rats on gut-brain communication, food intake, and body weight. Male Sprague-Dawley rats were maintained on regular chow, or 45% HF diet for nine weeks followed by three weeks of microbiota depletion using an antibiotic cocktail. The animals were then divided into four groups (n=10 each): - control group on regular chow, - chow fed animals that received antibiotics and microbiota from chow fed animals, - HF fed animals that received microbiota from chow fed animals, and - HF fed animals that received microbiota from HF fed animals. Animals were gavaged with donor microbiota for three consecutive days on week one and once a week thereafter for three more weeks. HF-LF animals received inulin as a prebiotic to aid the establishment of the lean microbiome.

RESULTS

We found that transferring a LF microbiota to HF fed animals (HF-LF) reduced caloric intake during the light phase when compared with HF-HF rats and prevented additional excessive weight gain. We did not observe significant changes in the density of vagal afferents terminating in the brainstem among the groups, however, HF-LF animals displayed an increase in postprandial activation of both primary sensory neurons innervating the GI tract and brainstem secondary neurons.

CONCLUSIONS

We concluded from these data that normalizing microbiota composition in obese rats improves gut-brain communication and restores normal feeding patterns which was associated with a reduction in weight gain.

摘要

背景

生活在胃肠道(GI)中的微生物(主要是细菌)群落被统称为肠道微生物群。胃肠道细菌在宿主免疫系统和新陈代谢的调节以及某些病理生理过程中发挥着积极作用。饮食是调节肠道微生物群组成的主要因素,最近的研究表明,高脂肪(HF)饮食会导致胃肠道细菌组成发生有害变化,即生态失调。高脂肪饮食诱导的微生物群生态失调与肠道-大脑迷走神经介导的信号系统的结构和功能变化有关,这与暴饮暴食和肥胖相关。尽管高脂肪饮食导致的微生物群组成变化足以改变迷走神经信号,但肥胖状态下恢复正常微生物群是否能改善肠道-大脑信号和代谢结果尚不清楚。在本研究中,我们评估了将瘦型肠道微生物群转移到肥胖、迷走神经功能受损的大鼠体内对肠道-大脑通讯、食物摄入和体重的影响。雄性Sprague-Dawley大鼠先食用常规饲料或45%高脂肪饮食9周,然后使用抗生素混合物进行3周的微生物群清除。然后将动物分为四组(每组n = 10): - 食用常规饲料的对照组, - 接受来自食用常规饲料动物的抗生素和微生物群的食用常规饲料动物, - 接受来自食用常规饲料动物的微生物群的高脂肪饮食喂养动物,以及 - 接受来自高脂肪饮食喂养动物的微生物群的高脂肪饮食喂养动物。在第1周连续3天给动物灌胃供体微生物群,此后每周1次,持续3周。高脂肪-低脂肪(HF-LF)组动物接受菊粉作为益生元以帮助建立瘦型微生物群。

结果

我们发现,与高脂肪-高脂肪(HF-HF)大鼠相比,将低脂肪微生物群转移到高脂肪饮食喂养的动物(HF-LF)中可减少光照期的热量摄入,并防止体重进一步过度增加。我们未观察到各组中终止于脑干的迷走神经传入纤维密度有显著变化,然而,HF-LF组动物在支配胃肠道的初级感觉神经元和脑干次级神经元的餐后激活方面有所增加。

结论

我们从这些数据中得出结论,肥胖大鼠的微生物群组成正常化可改善肠道-大脑通讯,并恢复正常的进食模式,这与体重增加减少相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb59/11160927/4b1ba337ecbd/nihpp-rs4438240v1-f0001.jpg

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