Highly branched neo-fructans (agavins) are natural prebiotics found in Agave plants, with a large capacity to mitigate the development of obesity and metabolic syndrome. Here, we investigated the impact of agavins intake on gut microbiota modulation and their metabolites as well as their effect on metabolic endotoxemia and low-grade inflammation in mice fed high-fat diet. Mice were fed with a standard diet (ST) and high-fat diet (HF) alone or plus an agavins supplement (HF+A) for ten weeks. Gut microbiota composition, fecal metabolite profiles, lipopolysaccharides (LPS), pro-inflammatory cytokines, and systemic effects were analyzed. Agavins intake induced substantial changes in gut microbiota composition, enriching Bacteroides, Parabacteroides, Prevotella, Allobaculum, and Akkermansia genus (LDA > 3.0). l-leucine, l-valine, uracil, thymine, and some fatty acids were identified as possible biomarkers for this prebiotic supplement. As novel findings, agavins supplementation significantly decreased LPS and pro-inflammatory (IL-1α, IL-1β, and TNF-α; p < 0.05) cytokines levels in portal vein. In addition, lipid droplets content in the liver and adipocytes size also decreased with agavins consumption. In conclusion, agavins supplementation mitigate metabolic endotoxemia and low-grade inflammation in association with gut microbiota regulation and their metabolic products, thus inducing beneficial responses on metabolic disorders in high-fat diet-fed mice.

Agavins are prebiotics and functional fiber that modulated the gut microbiota and metabolic status in obese mice. Here, we designed a placebo-controlled, double-blind, exploratory study to assess fluctuations in gastrointestinal (GI) tolerability-related symptoms to increasing doses of agavins in 38 lean and obese Mexican adults for five weeks and their impact on subjective appetite, satiety, metabolic markers, and body composition. All GI symptoms showed higher scores than placebo at almost every dose for both lean and obese groups. Flatulence caused an intense discomfort in the lean-agavins group at 7 g/day, while obese-agavins reported a mild-to-moderate effect for all five symptoms: no significant differences among 7, 10, and 12 g/day for flatulence, bloating, and diarrhea. Ratings for any GI symptom differed between 10 and 12 g/day in neither group. The inter-group comparison demonstrated a steady trend in GI symptoms scores in obese participants not seen for lean volunteers that could improve their adherence to larger trials. Only body weight after 10 g/day reduced from baseline conditions in obese-agavins, with changes in triglycerides and very-low-density lipoproteins compared to placebo at 5 g/day, and in total cholesterol for 10 g/day. Altogether, these results would help design future trials to evaluate agavins impact on obese adults.