Distinct Gut Microbiota Induced by Different Fat-to-Sugar-Ratio High-Energy Diets Share Similar Pro-obesity Genetic and Metabolite Profiles in Prediabetic Mice.

Kai Shan,Zhennan Gu,Hongyan Qu,Heyan Chen,Yumin Qi,Guoling Fu,Keru Zhou,Haiqin Chen,Rong Wang,Congmin Zhu,Wei Chen,Yong Q Chen,Liangfang Wang,Jiaqi Li,Jing Cui,Jack A Gilbert

doi:10.1128/msystems.00219-19

Kai Shan, Zhennan Gu + Show 14 more

Open Access

https://doi.org/10.1128/msystems.00219-19

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Abstract

Gut microbiota play important roles in host metabolism, especially in diabetes. However, why different diets lead to similar diabetic states despite being associated with different microbiota is not clear. Mice were fed two high-energy diets (HED) with the same energy density but different fat-to-sugar ratios to determine the associations between the microbiota and early-stage metabolic syndrome. The two diets resulted in different microbiota but similar diabetic states. Interestingly, the microbial gene profiles were not significantly different, and many common metabolites were identified, including l-aspartic acid, cholestan-3-ol (5β, 3α), and campesterol, which have been associated with lipogenesis and inflammation. Our study suggests that different metabolic-syndrome-inducing diets may result in different microbiota but similar microbiomes and metabolomes. This suggests that the metagenome and metabolome are crucial for the prognosis and pathogenesis of obesity and metabolic syndrome.IMPORTANCE Various types of diet can lead to type 2 diabetes. The gut microbiota in type 2 diabetic patients are also different. So, two questions arise: whether there are any commonalities between gut microbiota induced by different pro-obese diets and whether these commonalities lead to disease. Here we found that high-energy diets with two different fat-to-sugar ratios can both cause obesity and prediabetes but enrich different gut microbiota. Still, these different gut microbiota have similar genetic and metabolite compositions. The microbial metabolites in common between the diets modulate lipid accumulation and macrophage inflammation in vivo and in vitro This work suggests that studies that only use 16S rRNA amplicon sequencing to determine how the microbes respond to diet and associate with diabetic state are missing vital information.

Highlights

IMPORTANCE Various types of diet can lead to type 2 diabetes
Prediabetes can be seen as a curable disease state and a checkpoint for type 2 diabetes (T2D) [34]
It is important to clarify pathophysiological changes associated with prediabetes

Summary

RESULTS

The HF diet and HS diet both induce prediabetes in mice. Gut microbiota in mice with diet-induced obesity have been studied extensively. Weighted UniFrac tree analysis supported the clustering and showed that the control diet cluster was far away from the two HED clusters (Fig. 2D) These results indicate that diets with different fat-to-sugar ratios shape distinct gut microbiota in prediabetic mice. It is worth noting that changes at the genus level do not represent changes in all species of the genus (see Fig. S1 in the supplemental material) These results indicate that HF and HS diets induce two distinct patterns of obesity-associated gut microbiota in prediabetic mice. Common pathways were mainly involved in energy metabolism and biosynthesis of lipid and amino acids (Fig. 3H and Fig. S5) These results indicate that HF and HS diets enrich similar gene profiles despite shaping different microbiota. These data suggest the potential anti-inflammatory role of cholestan-3-ol (5␤, 3␣) and campesterol as well as a possible proinflammatory role of L-aspartic acid

DISCUSSION

MATERIALS AND METHODS

Results