Prebiotic Diet Modulates Gut Microbial Composition and Metabolic Functions in Metabolic Syndrome Patients: Follow‐Up of a Double Blind, Controlled, Crossover Intervention

Background/Aim Metabolic syndrome (MetS) afflicts 34% of American adults who are at increased risk for cardiovascular diseases. Resistant starch type 4 (RS4) is protective against MetS despite its limited digestion and absorption. However, the suggested prebiotic mechanism of action of RS4 through modulation of the gut‐microbiome has not been established, particularly in MetS patients. Here we aimed to elucidate the influence of RS4‐enriched diet on the gut microbial composition of MetS patients in association with improvements in body composition, immune, and metabolic functions. Methods/Results Twenty men and women with MetS received RS4‐enriched (30%, v/v in flour) or control‐flour diet (CF) for 12 weeks during a 26‐week double‐blind crossover study. No significant variation ( p >0.05) was observed in macronutrient and calorie intake between the intervention groups. RS4, compared with CF, reduced % body fat ( p =0.05), waist circumference (WC, p =0.06), hemoglobinA1C ( p =0.08), non‐high‐density lipoprotein (non‐HDL, p =0.003), total cholesterol (TC, p <0.001) but also HDL ( p =0.005). RS4 intake attenuated proinflammatory interleukin 6 ( p =0.04, compared to baseline), TNFα ( p =0.08) and increased beneficial circulatory adiponectin ( p =0.002, compared to baseline) levels. Differential alteration ( p <0.05) of 71 bacterial taxa by 16S‐rRNA gene‐sequencing were observed in the RS4‐group compared with the CF‐group. Parabacteroides distasonis ( q <0.001), Bifidobacterium adolescentis ( q =0.087), Bacteroides ovatus ( q =0.087), Ruminococcus lactaris ( q <0.001), Eubacterium oxidoreducens ( q <0.001), Clostridium leptum ( q =0.02), Bacteroides xylanisolvens ( q =0.037), Bacteroides acidifaciens ( q =0.038), and Christensenella minuta ( q =0.038) were enriched after RS4 intervention. Microbial changes associated ( p <0.05) with WC, body and fat masses, TC, non‐HDL, postprandial glucose, using abundance and binary metrics for 5,949 taxa. Bivariate analyses showed that RS4‐intervention established ( p <0.05) direct and inverse correlations among bacterial species and metabolic markers: adiponectin with two Bacterioides species (r>0.82) as well as TC‐ Oscillospira spp. (r=−0.60), TC‐ Parabacteroides distasonis (r=−0.57), TC‐ Odoribacter spp. (r=−0.55), and TC‐ Bacteroides plebius (r=−0.52). RS4 intervention generally enriched bacteroidetes that help with degradation and fermentation of dietary starch. Analyses by gas chromatography‐ mass spectrometry revealed increased fecal short chain fatty acids (SCFA) from bacterial fermentation: butyrate ( p =0.001), propionate ( p =0.005), valerate ( p =0.001), isovalerate ( p =0.012), and acetate ( p =0.07). Conclusion These data suggest that the biological activity of RS4 is derived from its prebiotic actions in the intestine through selective changes in the gut microbial and SCFA compositions in MetS patients. The RS4‐induced improvements in the host metabolic functions have important implications for cardiometabolic disease prevention. Trial registered as NCT01887964 at clinicaltrials.gov Support or Funding Information This work is supported by MGP Ingredients, Atchison KS, USDA National Institute of Food and Agriculture Hatch project [1004817], National Institutes of Health [R00AT4245], Sanford Health – South Dakota State University Collaborative Research program [SA1500625] and by the SD Board of Regents R&D Innovation program [SA1500624].