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Ketogenic Diets Induced Glucose Intolerance and Lipid Accumulation in Mice with Alterations in Gut Microbiota and Metabolites.

ABSTRACT: The ketogenic diet (KD), which can induce changes in gut microbiota, has shown benefits for epilepsy and several neurodegenerative diseases. However, the effects of a KD on glucose and lipid metabolism remain inconclusive. Using two formulas of ketogenic diets (KDR with 89.5% fat and KDH with 91.3% fat), which are commonly used in mouse trials, we found that KDR but not KDH induced insulin resistance and damaged glucose homeostasis, while KDH induced more fat accumulation in mice. Further study showed that KD impacted glucose metabolism, which was related to the sources of fat, while both the sources and proportions of fat affected lipid metabolism. And the KD widely used in human studies still induced insulin resistance and fat accumulation in mice. Moreover, KDs changed the gut microbiota and metabolites in mice, and the sources and proportions of fat in the diets respectively changed the abundance of specific bacteria and metabolites which were correlated with parameters related to glucose intolerance and lipid accumulation. Overall, our study demonstrated that the metabolic disorders induced by KDs are closely related to the source and proportion of fat in the diet, which may be associated with the changes of the gut microbiota and metabolites.IMPORTANCE The ketogenic diet with extremely high fat and very low carbohydrate levels is very popular in society today. Although it has beneficial effects on epilepsy and neurodegenerative diseases, how ketogenic diets impact host glucose and lipid metabolism and gut microbiota still needs further investigation. Here, we surveyed the effects of two ketogenic diets which are commonly used in mouse trials on metabolic phenotypes, gut microbiota, and metabolites in mice. We found that both ketogenic diets impaired glucose and lipid metabolism in mice, and this may be due to the sources and proportions of fat in the diets. This work highlights the potential risk of glucose and lipid metabolism disorders and the importance of evaluating the sources and proportions of fat in the diets, when using ketogenic diets for weight loss and the treatment of diseases.

SUBMITTER: Li Y

PROVIDER: S-EPMC8092315 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:This study aimed to investigate insomnia-related alterations in gut microbiota and their association with serum metabolites. A total of 24 patients with insomnia disorder and 22 healthy controls were recruited. The fecal and serum samples were collected. The 16s rRNA sequencing and bioinformatics analysis were conducted to explore insomnia-related changes in the diversity, structure, and composition of the gut microbiota. UPLC-MS was performed to identify insomnia-related serum metabolites. Spearman correlation analysis was used to investigate the correlations between insomnia-related gut bacteria and the serum metabolites. Despite the nonsignificant changes in the diversity and structure of gut microbiota, insomnia disorder patients had significantly decreased family Bacteroidaceae, family Ruminococcaceae, and genus Bacteroides, along with significantly increased family Prevotellaceae and genus Prevotella, compared with healthy controls. Genus Gemmiger and genus Fusicatenibacter were dominant in patients with insomnia disorder, whereas genus Coprococcus, genus Oscillibacter, genus Clostridium XI, and family Peptostreptococcaceae were dominant in healthy controls. The UPLC-MS analysis identified 97 significantly decreased metabolites and 74 significantly increased metabolites in the serum samples of patients with insomnia disorder, compared with those of healthy controls. KEGG enrichment analysis revealed 1 significantly upregulated metabolic pathway and 16 downregulated metabolic pathways in patients with insomnia disorder. Furthermore, Spearman correlation analysis unveiled significant correlations among the altered bacteria genus and serum metabolites. Patients with insomnia disorder have differential gut microbiota and serum metabolic profiles compared with healthy controls. The alterations in gut microbiota were correlated with specific serum metabolites, suggesting that some serum metabolites might mediate gut microbiota-brain communication in the pathogenesis of insomnia disorder.

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Ketogenic Diets Induced Glucose Intolerance and Lipid Accumulation in Mice with Alterations in Gut Microbiota and Metabolites.

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