# The effects of a very low-energy ketogenic therapy on body composition, gut microbiota and metabolites in overweight subjects

**Authors:** Yeganeh Manon Khazrai, Claudia Di Rosa, Annamaria Altomare, Marta Giovanetti, Ludovica Di Francesco, Greta Lattanzi, Chiara Spiezia, Antonella Simone, Federica Coccaro, Giulia Costa, Michele Pier Luca Guarino, Silvia Manfrini

PMC · DOI: 10.3389/fnut.2025.1714444 · 2026-01-09

## TL;DR

A 28-day low-energy ketogenic diet reduced weight and altered gut bacteria and stool metabolites in overweight individuals.

## Contribution

This study explores the effects of a ketogenic therapy on gut microbiota and metabolites alongside weight loss in overweight subjects.

## Key findings

- Significant reductions in body weight, BMI, and fat mass were observed.
- Gut microbiota showed decreased Firmicutes and increased Bacteroidetes and Verrucomicrobia.
- Stool metabolites included increased propionate and GABA, and decreased butyrate and lactate.

## Abstract

Obesity is associated with chronic diseases and gut-brain axis disruptions, with diet influencing gut microbiota. This single-arm, uncontrolled study evaluated the effects of a 28 – day Very Low-Energy Ketogenic Therapy (VLEKT) on body weight, gut microbiota, and stool-derived metabolites in individuals with excess weight. Forty-one subjects underwent baseline (T0) assessment including anthropometry, bioimpedance analysis, gut microbiota profiling and completed FAST questionnaire before and after 28 days of VLEKT with meal replacements (T1). Follow-up was conducted at T1. Thirty-one participants completed the intervention (T1). Results showed significant reductions in body weight, BMI, and fat mass. Microbiota analysis revealed decreased Firmicutes and Actinobacteria, and increased Bacteroidetes and Verrucomicrobia. Genus-level changes included increases in Bacteroides, Parabacteroides, and Akkermansia, and decreases in Streptococcus, Dorea, Blautia, Bifidobacterium, and Ruminococcus. Stool metabolites showed decreased butyrate and lactate and increased propionate, vitamin K2, and GABA. Because the study lacked a control group and did not include systemic biomarkers or biochemical confirmation of ketosis, microbiota and metabolite changes cannot be linked to physiological effects. Overall, findings indicate short-term weight loss and stool microbiota modulation, but all microbiota-related outcomes remain exploratory due to the small sample size, short duration, and uncontrolled design.

## Linked entities

- **Diseases:** obesity (MONDO:0011122)

## Full-text entities

- **Diseases:** overweight (MESH:D050177), excess weight (MESH:D015431), Obesity (MESH:D009765), ketosis (MESH:D007662)
- **Chemicals:** vitamin K2 (MESH:D024482), GABA (MESH:D005680), propionate (MESH:D011422), butyrate (MESH:D002087), lactate (MESH:D019344)
- **Species:** Streptococcus (genus) [taxon 1301], Parabacteroides (genus) [taxon 375288], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Bacteroides (genus) [taxon 816], Ruminococcus (genus) [taxon 1263], Bifidobacterium (genus) [taxon 1678], Akkermansia (genus) [taxon 239934]

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12828980/full.md

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Source: https://tomesphere.com/paper/PMC12828980