Abstract

We investigated the association between microbiome composition in peyer's patches in small intestine and high‐fat diet‐induced obesity in mice. C57L/6J male mice were fed either low fat (10% calories from fat, CT) or high fat (50% calories from fat) diets for 25 weeks, and the high‐fat diet‐fed mice were classified to obesity prone (OP) or obesity resistant (OR) based on their body weight gains. Microbiome was harvested from peyer's patches analyzed for bacterial composition. Our results showed that the numbers of peyer's patches inhabiting Lactobacillus were significantly lower in OP mice. Further selection of Lactobacillus generated 52, 18 and 22 isolates from CT, OP and OR mice, respectively. They belonged to 13 different phenotypes. Lactobacillus reuteri was the most abundant strain, but its abundance in OP mice was much lower. There were 8 subgroups of these L. reuteri. L. reuteri L3 and L. reuteri L8 were the specific strain found in CT and OP mice, respectively. Oxidative resistant Lactobacillus was much higher in high‐fat diet‐fed mice. Co‐cultured with peyer's patches cells, L8 induced higher production of pro‐inflammatory cytokine such as IL‐6, IL‐12 and TNF‐alpha, whereas, L3 induced higher production of anti‐inflammatory cytokine such as IL‐10. Overall, our results suggested that high‐fat diet may induce oxidative stress in small intestine that promotes the growth of pro‐inflammatory Lactobacillus strains with high resistance to oxidative stress, and these phenomena is specific for OP mice. 
 This work was supported by National Natural Science Foundation of China (No. 31201805).

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