Taxonomic and functional shifts in the microbiome of severely obese, prediabetic patients: Ketogenic diet versus energy-matched standard diet.
Publisher DOI
PubMed ID
41395693
Abstract
Aims
Obesity and type 2 diabetes mellitus (T2DM) are among the leading global health challenges of the 21st century. While caloric restriction remains the cornerstone of weight loss interventions, ketogenic diets (KD), characterised by low carbohydrate and high fat intake, have been shown to improve metabolic health partly by modulating the gut microbiome. This study investigated the effects of a short-term KD on gut microbiome composition and function in severely obese, prediabetic patients, compared to an energy-matched standard diet (SD).Methods
In a randomised trial, patients with BMI >35 kg/m2 and prediabetes underwent either a 2-week KD or isocaloric SD, both inducing a 30% energy deficit. Faecal samples collected before and after the intervention, alongside samples from healthy controls, were analysed by whole-genome metagenomic sequencing.Results
At baseline, prediabetic patients exhibited greater interindividual variability and lower alpha diversity than healthy controls. KD resulted in a significant reduction of alpha diversity, largely driven by a selective loss of Lachnospiraceae, with a concomitant increase in Bacteroidaceae. Functional profiling revealed that KD, but not SD, altered genes coding for enzymes involved in energy metabolism, amino acid synthesis, nucleic acid activity, RNA modification, and vitamin biosynthesis. Additionally, serum acetate levels increased significantly following KD.Conclusions
These findings underscore that KD, independent of caloric intake, acutely remodels the gut microbiome's taxonomic and functional landscape, highlighting the microbiome as a potential mediator of KD's metabolic effects.
Obesity and type 2 diabetes mellitus (T2DM) are among the leading global health challenges of the 21st century. While caloric restriction remains the cornerstone of weight loss interventions, ketogenic diets (KD), characterised by low carbohydrate and high fat intake, have been shown to improve metabolic health partly by modulating the gut microbiome. This study investigated the effects of a short-term KD on gut microbiome composition and function in severely obese, prediabetic patients, compared to an energy-matched standard diet (SD).Methods
In a randomised trial, patients with BMI >35 kg/m2 and prediabetes underwent either a 2-week KD or isocaloric SD, both inducing a 30% energy deficit. Faecal samples collected before and after the intervention, alongside samples from healthy controls, were analysed by whole-genome metagenomic sequencing.Results
At baseline, prediabetic patients exhibited greater interindividual variability and lower alpha diversity than healthy controls. KD resulted in a significant reduction of alpha diversity, largely driven by a selective loss of Lachnospiraceae, with a concomitant increase in Bacteroidaceae. Functional profiling revealed that KD, but not SD, altered genes coding for enzymes involved in energy metabolism, amino acid synthesis, nucleic acid activity, RNA modification, and vitamin biosynthesis. Additionally, serum acetate levels increased significantly following KD.Conclusions
These findings underscore that KD, independent of caloric intake, acutely remodels the gut microbiome's taxonomic and functional landscape, highlighting the microbiome as a potential mediator of KD's metabolic effects.
Date Issued
2026-03
Publication Type
Article
Subject(s)
Subjects
clinical trial
•
dietary intervention
•
energy regulation
•
obesity therapy
Language(s)
en
Author(s)
Stone, June | |
Meinel, Dominik M. |
Journal
Diabetes, Obesity and Metabolism: A Journal of Pharmacology and Therapeutics
Publisher
Wiley
ISSN
1463-1326
1462-8902
Related Collection(s)
Access(Rights)
open.access