Low-calorie diet intervention ameliorates gut microbiota dysbiosis and metabolic changes in obese patients with type 2 diabetes under standard care.

Background: Dietary interventions can modulate the gut bacteria community (microbiota) and offer a complementary strategy for improving metabolic control in type 2 diabetes (T2D). This pilot study evaluated clinical clinical outcomes and gut microbiota changes following a structured low-calorie diet (LCD) intervention in obese T2D individuals under standard care. Methods: Twenty obese T2D patients were randomized into an intervention group (n = 15) (6-week 1000-1200 kcal/day of glycemic and metabolic control LCD), or a matched control group (n = 5). Clinical parameters and fecal microbiota profiles were assessed at baseline, week 6, and week 12. Results: The intervention group showed clinical trends toward improved glycemic and metabolic parameters, including reductions in fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and lipid levels (i.e., cholesterol) (P > 0.05), accompanied by significant loss of body weight, body mass index (BMI), and body fat (P < 0.05). Four intervention participants (26.7 %) achieved normoglycemia without glucose-lowering medication. Gut microbiota analyses revealed significant alterations in alpha and beta diversity over time in the intervention group (AMOVA: P(control baseline, intervention 12-week) = 0.025 and P(intervention baseline, intervention 12-week) = 0.002), with increased abundance of beneficial genera i.e. Streptococcus, Bifidobacterium and Lactobacillus, and enrichment of Actinobacteria, Candidatus Saccharibacteria (TM7), and Firmicutes at week 12. Linear discriminant analysis effect size (LEfSe) analysis identified distinct microbial biomarkers differentiating groups. Microbial functional predictions revealed significantly decreased inferred activity in pathways related to adipocytokine signaling, D-glutamine and D-glutamate metabolism, and type I diabetes mellitus (P < 0.05); however, these predictions were computational inferences and not experimentally validated. Conclusion: A structured LCD combined with standard care led to metabolic improvement and remodeling of gut microbiota trend in obese Thai individuals with T2D. The findings support the dietary interventions to beneficially modulate the gut microbiome and metabolic health, while highlighting the need for larger studies and functional validation.