A Bifidogenic Prebiotic Supplement Beneficially Alters Gut Microbial Composition, Activity, and Plasma Metabolites in Healthy Individuals Consuming Low Fiber Diets

A randomized order, double-blinded, placebo-controlled cross-over intervention study was conducted to test the effectiveness of a prebiotic supplement in healthy participants consuming a diet low in fiber. This clinical trial was registered at clinicaltrials.gov as NCT03785860. Fecal microbial DNA was extracted and sequenced with shallow shotgun sequencing for metagenomics. Plasma metabolites were analyzed with untargeted liquid chromatography-mass spectrometry for metabolomics. Statistical analyses were performed with the package edgeR in R version 4.0.2. For each outcome, linear mixed models were used with fixed effects of treatment, treatment order, and their interaction and random effect of individual participants. From the metagenomic analysis, the relative abundance of the genus Bifidobacterium and several bifidobacterial species increased after prebiotic supplementation compared to the placebo. Additionally, gene counts of genes sacA, xfp, xpk associated with prebiotic utilization significantly increased after the prebiotic supplement. Other genes that increased in counts were poxB and ackA, which are related to acetate metabolism. Changes in bifidobacteria abundance were positively correlated with changes in genes related to fructose and choline metabolism, and negatively correlated with a gene that encodes for acetate kinase. Plasma concentrations of indolepropionate significantly increased whereas choline and several acylcholines such as stearoylcholine, dihomo-linolenoyl-choline, linoleoylcholine, arachidonoylcholine, palmitoylcholine, and oleoylcholine significantly decreased after the prebiotic compared to the placebo arm. The results of this study demonstrate that a convenient, easy to use bifidogenic prebiotic supplement beneficially altered gut microbial composition and activity, which was reflected in changes in plasma metabolites in healthy individuals consuming low fiber diets.