Microbial enterotypes beyond genus level: Bacteroides species as a predictive biomarker for weight change upon controlled intervention with arabinoxylan oligosaccharides in overweight subjects

Recent studies indicate that microbial enterotypes may influence the beneficial effects of wholegrain enriched diets including bodyweight regulation. In a 4-week intervention trial, overweight subjects were randomized to consume either arabinoxylan-oligosaccharides (AXOS) (10.4 g/d) from wheat bran or polyunsaturated fatty acids (PUFA) (3.6 g/d). In the present study, we have stratified the subjects participating in the intervention (n = 29) according to the baseline Prevotella-to-Bacteroides (P/B) ratios through a post-hoc analysis and applied a linear mixed model analysis to identify the influence of this P/B ratio on the differences in weight changes in the intervention arms. Following AXOS consumption (n = 15), the high P/B group showed no bodyweight changes [-0.14 kg (95% CI: -0.67; 0.38, p = .59)], while the low P/B group gained 0.65 kg (95% CI: 0.16; 1.14, p = .009). Consequently, a difference of -0.79 kg was found between P/B groups (95% CI: -1.51; -0.08, p = .030). No differences were found between P/B groups following PUFA consumption (0.61 kg, 95% CI: -0.13; 1.35, p = .10). Among the Bacteroides species, B. cellulosilyticus relative abundance exhibited the highest positive rank correlation (Kendall's tau = 0.51, FDR p = .070) with 4-week weight change on AXOS, and such association was further supported by using supervised classification methods (Random Forest). We outlined several carbohydrate-active enzyme (CAZy) genes involved in xylan-binding and degradation to be enriched in B. cellulosilyticus genomes, as well as multiple accessory genes, suggesting a supreme AXOS-derived glycan scavenging role of such species. This post-hoc analysis, ensuring species and strain demarcation at the human gut microbiota, permitted to uncover the predictive role of Bacteroides species over P/B enterotype in weight gain during a fiber-based intervention. The results of this pilot trial pave the way for future assessments on fiber fermentation outputs from Bacteroides species affecting lipid metabolism in the host and with direct impact on adiposity, thus helping to design personalized interventions.