Background: Dietary intervention is a cornerstone of weight loss therapies. In obesity, a dysbiotic gut microbiota (GM) is characterized by high levels of Bacteroides lineages and low diversity. We examined the GM composition changes, including the Bacteroides 2 enterotype (Bact2), in a real-world weight loss study in subjects following a high-protein hypocaloric diet with or without a live microorganisms (LMP) supplement. Method: 263 volunteers were part of this real-world weight loss program. The first phase was a high-protein low-carbohydrate calorie restriction diet with or without LMP supplements. Fecal samples were obtained at baseline and after 10% weight loss for 163 subjects. Metagenomic profiling was obtained by shotgun sequencing. Results: At baseline, the Bact2 enterotype was more prevalent in subjects with aggravated obesity and metabolic alterations. After weight loss, diversity increased and Bact2 prevalence decreased in subjects with lower GM diversity at baseline, notably in LMP consumers. Significant increases in Akkermansia muciniphila and Parabacteroides distasonis and significant decreases of Eubacterium rectale, Streptococcus thermophilus and Bifidobacterial lineages were observed after weight loss. Conclusions: Baseline microbiome composition is associated with differential changes in GM diversity and Bact2 enterotype prevalence after weight loss. Examining these signatures could drive future personalized nutrition efforts towards more favorable microbiome compositions.

BACKGROUND: In order to maintain body weight regulation, leptin directly or indirectly signals nutritional changes to key organs, but little is known about its target genes in human adipose tissue. Leptin receptor loss of function is a unique way to explore the role of leptin in the regulation of adipose tissue. OBJECTIVE: We studied the consequences of the absence of leptin signaling on adipocyte gene expression in two girls with a mutation in the leptin receptor. The expression levels of the ob gene and adipocyte transcription factors (SREBP1c, C/EPBα, β, PPARγ1, γ2) were quantified by RT-PCR in subcutaneous adipose tissue of these patients and of 10 morbidly obese women. RESULTS: Ob mRNA levels in subjects lacking the leptin receptor were not overexpressed but were in the range that could be expected from their BMI (58 and 26 amol/µg total mRNA, range in obese women: 26–69). Expression of the five transcription factors was also in the same range in the affected patients and in morbidly obese women (7.7 and 6.8 amol/µg total mRNA, range: 2.2–9.4 for SREBP1c, 159 and 51 range: 51–406 for C/EPBα, 6.1 and 3.3 range: 2.4–24.8 for C/EPBβ, 16.7 and 27.4 range: 9.4–29.7 for PPARγ1 and 1.7 and 5.4 amol/µg total mRNA range: 1.7–8.8 for PPARγ2). Significant correlation was found between the mRNA levels of leptin and PPARγ2 and leptin and C/EBPα whereas no correlation was observed between leptin and SREBP1c, PPARγ1, or C/EBPβ mRNA levels. CONCLUSION: In patients lacking leptin signaling, the fact that ob gene expression is adequately adapted to their body fat mass argues against a direct negative feedback loop in the regulation of leptin expression in humans. The normal expression of several transcription factors, known to be dependent of the nutritional status, suggests that leptin is not a major contributor of their in vivo transcriptional regulation in human adipose tissue.