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

## TL;DR

A short-term ketogenic diet changes gut bacteria and their functions in obese, prediabetic patients, potentially improving metabolic health.

## Contribution

The study shows that a ketogenic diet, not just calorie restriction, alters gut microbiome diversity and function in prediabetic patients.

## Key findings

- KD significantly reduced gut microbiome alpha diversity, especially decreasing Lachnospiraceae and increasing Bacteroidaceae.
- KD altered genes related to energy metabolism, amino acid synthesis, and vitamin biosynthesis, unlike the standard diet.
- Serum acetate levels increased significantly following the ketogenic diet.

## Abstract

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).

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.

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.

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.