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

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 <i>Bacteroides, Parabacteroides</i>, and <i>Akkermansia</i>, and decreases in <i>Streptococcus, Dorea, Blautia, Bifidobacterium</i>, and <i>Ruminococcus.</i> 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.