The occurrence of obesity and related metabolic disorders is rising, necessitating effective long-term weight management strategies. With growing interest in the potential role of gut microbes due to their association with responses to different weight loss diets, understanding the mechanisms underlying the interactions between diet, gut microbiota, and weight loss remains a challenge. This study aimed to investigate the potential impact of a multiphase dietary protocol, incorporating an improved ketogenic diet (MDP-i-KD), on weight loss and the gut microbiota. Using metagenomic sequencing, we comprehensively analyzed the taxonomic and functional composition of the gut microbiota in 13 participants before and after a 12-week MDP-i-KD intervention. The results revealed a significant reduction in BMI (9.2% weight loss) among obese participants following the MDP-i-KD intervention. Machine learning analysis identified seven key microbial species highly correlated with MDP-i-KD, with Parabacteroides distasonis exhibiting the highest response. Additionally, the co-occurrence network of the gut microbiota in post-weight-loss participants demonstrated a healthier state. Notably, metabolic pathways related to nucleotide biosynthesis, aromatic amino acid synthesis, and starch degradation were enriched in pre-intervention participants and positively correlated with BMI. Furthermore, species associated with obesity, such as Blautia obeum and Ruminococcus torques, played pivotal roles in regulating these metabolic activities. In conclusion, the MDP-i-KD intervention may assist in weight management by modulating the composition and metabolic functions of the gut microbiota. Parabacteroides distasonis, Blautia obeum, and Ruminococcus torques could be key targets for gut microbiota-based obesity interventions.

This study aimed to investigate the effects of a hypocaloric balanced diet (HBD) on anthropometric measures and gut microbiota of 43 people with obesity. Fecal samples were collected from the study subjects at weeks 0 and 12, and a detailed analysis of gut microbiota was performed using 16S rRNA gene sequencing. By comparing anthropometric measures and microbiota changes in subjects before and after the HBD intervention, we revealed the potential effects of HBD on weight loss and gut microbiota. Our results indicated that the HBD resulted in a significant decrease in body mass index (BMI), and most of the physiological indicators were decreased to a greater degree in the effective HBD group (EHBD, weight loss ≥ 5%) than in the ineffective HBD group (IHBD, weight loss < 5%). The HBD intervention also modified the gut microbiota of the subjects with obesity. Specifically, Blautia, Lachnoclostridium, Terrisporobacter, Ruminococcus (R. torques, R. gnavus), and Pseudomonas were significantly reduced. In addition, we employed machine learning models, such as XGBRF and GB models, to rank the importance of various features and identified the top 10 key bacterial genera involved. Gut microbiota co-occurrence networks showed the dominance of healthier microbiota following successful weight loss. These results suggested that the HBD intervention enhanced weight loss, which may be related to diet-induced changes in the gut microbiota.

Purpose: The aim of the present study was to investigate the effect and safety of a multiphase modified ketogenic diet (MMKD) compared to beinaglutide treatment or lifestyle modification (LM) alone on weight loss in obese patients in China. Patients and Methods: The present study was conducted in adults with obesity who did not have diabetes with two phases as follows: a 4-week run-in phase to guide diet and exercise, followed by a 12-week intervention phase aiming to lose weight. All participants performed aerobic and resistance exercise, and they were free to select any one of three weight-loss strategies as follows: LM group, 12 weeks of hypocaloric balanced diet (HBD); MMKD group, two cycles of a multiphase diet with each cycle comprised of 2 weeks of ketogenic diet (KD), 2 weeks of transition diet and 2 weeks of HBD; and beinaglutide group, 12 weeks of HBD plus daily injection of beinaglutide (0.4 mg per day). Body weight, body composition and metabolic variables were measured before and after the 12 weeks of treatment. Results: All intervention strategies had significant weight loss, and the MMKD led to greater weight loss than LM (difference, − 3.7 kg; 95% confidence interval [CI], − 6.1 to − 1.4; P = 0.001) but not beinaglutide (difference, − 1.5 kg; 95% CI, − 4.3 to 1.3; P = 0.587). Waist circumference (WC), fat mass, body fat percentage (BFP) and visceral fat area (VFA) were also significantly decreased, and the MMKD had a greater effect on these parameters than LM or beinaglutide. In addition, significant reductions in blood pressure and homoeostatic model assessment of insulin resistance (HOMA-IR) were observed in all three groups, but the MMKD resulted in the most significant improvement in insulin resistance. Almost no adverse events, except for two cases of dizziness, were observed in the MMKD group, which was significantly fewer events than the other two groups. Conclusion: These findings demonstrated that the MMKD is an effective and safe treatment for weight loss, thus providing an additional option for obese Chinese patients.