Gut microbiota changes associated with low-carbohydrate diet intervention for obesity

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 2-week intervention with KDs, mice fed
on KD1 displayed symptoms related to obesity, whereas KD2-fed 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.

DOI: 10.3389/fendo.2024.1446287
PMCID: PMC11466860
PMID: 39398341 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare that the research was
conducted in the absence of any commercial or financial relationships that could
be construed as a potential conflict of interest. The author(s) declared that
they were an editorial board member of Frontiers, at the time of submission.
This had no impact on the peer review process and the final decision.