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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Gut Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1446287
This article is part of the Research Topic The Mechanism in Gut Microbiota of Diabetes and Endocrine Complications: Preventive and Therapeutic Target View all 3 articles

The gut microbiota changed by ketogenic diets contribute to glucose intolerance rather than lipid accumulation

Provisionally accepted
Wei Li Wei Li Mengxue Gong Mengxue Gong Zhiyi Wang Zhiyi Wang Han Pan Han Pan Yue Li Yue Li Chenhong Zhang Chenhong Zhang *
  • Shanghai Jiao Tong University, Shanghai, China

The final, formatted version of the article will be published soon.

    The ketogenic diet (KD) is a popular option for managing body weight, though its influence on glucose and lipid metabolism was still inconclusive. Gut microbiota is modulated by dietary pattens and has been associated with the changes of metabolic homeostasis induced by KD. Here, we found that two types of KDs, KD1 (8.8% carbohydrate, 73.4% fat, 17.9% protein, 5.7 kcal/g) and KD2 (0.4% carbohydrate, 93.2% fat, 6.4% protein, 6.7 kcal/g), induced changes of gut microbiota and its metabolites, contributing to glucose intolerance but not lipid accumulation in mice. Following a 2week intervention with KDs, mice fed on KD1 displayed symptoms related to obesity, whereas KD2fed mice exhibited a decrease in body weight but had severe hepatic lipid accumulation and abnormal fatty acid metabolism, while both KDs led to significant glucose intolerance. Compared to the mice fed on a standard chow diet, the conventional mice fed on both KD1 and KD2 had significant shifted gut microbiota, lower levels of short chain fatty acids (SCFAs) and composition alteration of cecal bile acids. By using an antibiotic cocktail (ABX) to deplete most of the gut microbiota in mice, we found the disturbances induced by KDs in lipid metabolism were similar in the ABX-treated mice to their conventional companions, but the disturbances in glucose metabolism were absent in the ABX-treated mice. In conclusion, these findings suggest that ketogenic diets disrupted glucose and lipid metabolism, at least in mice, and highlight the gut microbial culprits associated with KD induced glucose intolerance rather than lipid accumulation.

    Keywords: Ketogenic Diet, Gut Microbiota, Glucose and lipid metabolism, SCFA, Bile acid

    Received: 09 Jun 2024; Accepted: 09 Sep 2024.

    Copyright: © 2024 Li, Gong, Wang, Pan, Li and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Chenhong Zhang, Shanghai Jiao Tong University, Shanghai, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.