High-Fat Diet Induces Dysbiosis of Gastric Microbiota Prior to Gut Microbiota in Association With Metabolic Disorders in Mice.

Cong He,Yanshu Li,Yin Zhu,Dandan Cheng,Nonghua Lu,Chao Peng

doi:10.3389/fmicb.2018.00639

Cong He, Yanshu Li + Show 4 more

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https://doi.org/10.3389/fmicb.2018.00639

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Abstract

Accumulating evidence suggests that high-fat diet (HFD) induced metabolic disorders are associated with dysbiosis of gut microbiota. However, no study has explored the effect of HFD on the gastric microbiota. This study established the HFD animal model to determine the impact of HFD on the gastric microbiota and its relationship with the alterations of gut microbiota. A total of 40 male C57BL/6 mice were randomly allocated to receive a standard chow diet (CD) or HFD for 12 weeks (12CD group and 12HFD group) and 24 weeks (24CD group and 24HFD group) (n = 10 mice per group). Body weight and length were measured and Lee’s index was calculated at different time points. The insulin sensitivity and serum levels of metabolic parameters including blood glucose, insulin and lipid were also evaluated. The gastric mucosa and fecal microbiota of mice were characterized by 16S rRNA gene sequencing. The body weight was much heavier and the Lee’s index was higher in 24HFD group than 12HFD. The insulin resistance and serum level of lipid were increased in 24HFD group compared to 12HFD, indicating the aggravation of metabolic disorders as HFD went on. 16S rRNA gene sequencing showed dysbiosis of gastric microbiota with decreased community diversity while no significant alteration in gut microbiota after 12 weeks of HFD. The phyla Firmicutes and Proteobacteria tended to increase whereas Bacteroidetes and Verrucomicrobia decrease in the gastric microbiota of 12HFD mice compared to 12CD. Moreover, a remarkable reduction of bacteria especially Akkermansia muciniphila, which has beneficial effects on host metabolism, was observed firstly in the stomach of 12HFD group and then in the gut of 24HFD group, indicating the earlier alterations of microbiota in stomach than gut after HFD. We also found structural segregation of microbiota in the stomach as well as gut between 12HFD and 24HFD group, which is accompanied by the aggregation of metabolic disorders. These data suggest that HFD affects not only gut microbiota but also gastric microbiota and the disruption of microbial ecosystem in the digestive tract may play a part in the development and progression of metabolic diseases although molecular mechanism requires further investigation.

Highlights

With the rapid development of the economy, secondary lifestyles and the intake of a high-fat diet have increased dramatically, leading to the prevalence of overweight and obesity worldwide
The difference in Lee’s index, which reveals the obesity of mice, between the chow diet (CD) and high-fat diet (HFD) groups was more remarkable at 24 weeks than at 12 weeks
We found that the HFD group at 24 weeks displayed more severe insulin resistance than at 12 weeks as revealed by intraperitoneal insulin tolerance test (IPITT) (p < 0.05)

Summary

Introduction

With the rapid development of the economy, secondary lifestyles and the intake of a high-fat diet have increased dramatically, leading to the prevalence of overweight and obesity worldwide. Obesity is the excess or abnormal accumulation of fat or adipose tissue in the body that may impair health. It is the most common risk factor for metabolic disorders such as type 2 diabetes, cardiovascular disease, fatty liver and even cancer. Preventive and therapeutic strategies to reduce the morbidity and mortality caused by obesity are important. Recent mounting evidence suggests that the gut microbiota is involved in the development of obesity in animals and humans (Zhao, 2013). Germ-free mice are leaner than conventionally raised mice and are protected against diet-induced obesity, which further verifies the causal relationship between gut microbiota and obesity (Backhed et al, 2007)

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