Taxonomic and functional shifts in the microbiome of severely obese, prediabetic patients: Ketogenic diet versus energy-matched standard diet.

aimsObesity 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).

methodsIn a randomised trial, patients with BMI >35 kg/m

resultsAt 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.

conclusionsThese 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.