Differential effects of inulin and fructooligosaccharides on gut microbiota composition and glycemic metabolism in overweight/obese and healthy individuals: a randomized, double-blind clinical trial

Modulating the gut microbiota with prebiotics is a promising strategy for managing metabolic diseases. However, the clinical effects on glycemic metabolism across different populations remain uncertain. In this study, we conducted a randomized, double-blind investigation to examine the impact of inulin and fructooligosaccharides (FOS) on glycemic metabolism in overweight/obese and healthy adults. A total of 131 adults were included, with 44 receiving inulin, 43 receiving FOS, and 44 receiving placebo over a period of 4 weeks. Blood and fecal samples were collected before and after the intervention, and various metabolic parameters, gut microbiota composition, and metabolites were analyzed. Placebo had no effect on glycemic metabolism or gut microbiota. Inulin significantly reduced glucose levels at 1 h (Cohen's d = 0.71, p = 0.041) and 2 h (Cohen's d = 0.73, p = 0.028) during oral glucose tolerance test (OGTT), increased fasting insulin (Cohen's d = 0.70, p = 0.008), and lowered homocysteine (HCY) levels (Cohen's d = 0.76, p = 0.014) in overweight/obese individuals. These effects were not observed in healthy individuals. In contrast, although FOS significantly decreased HCY (Cohen's d = 0.72, p = 0.023), it did not improve glycemic metrics in either group. Inulin also reduced the abundance of Ruminococcus by 72.0% (from 1.661% ± 1.501% to 0.465% ± 0.594%), positively correlating with improved glycemic outcomes. Propionate levels decreased significantly in both overweight/obese (Cohen's d = 0.89, p = 0.014) and healthy participants (Cohen's d = 1.19, p = 0.020) following inulin. Functional prediction of gut microbiota revealed upregulation of microbial folate and glutathione metabolism with inulin, and purine metabolism with FOS. Practically, inulin may be more suitable for managing glycemic dysregulation in overweight or obese individuals, while FOS may be considered for HCY reduction in individuals with normal glycemic status. Such targeted use of prebiotics could complement existing dietary and pharmacologic strategies in personalized metabolic care. ChiCTR-IOR-17010574.