Prolonged efficacy of Bifidobacterium lactis in the treatment of functional dyspepsia

Abstract Background Current treatment for functional dyspepsia (FD) has limited and unsustainable efficacy. Probiotics have the potential to alleviate FD; However, the underlying mechanism remains unclear. This study aimed to evaluate the effect and mechanism of probiotics in alleviating FD. Methods A randomized, positive-drug and placebo-controlled clinical trial was conducted; 200 FD patients were randomly divided into four groups (placebo, positive control [proton pump inhibitors, PPI] or Bifidobacterium lactis BL-99 [low, high doses]). The clinical response rates in 8-week treatment, 2-week follow-up and 6-week questionnaire survey periods were recorded. Faecal microbiota and metabolites were assessed by metagenomics, un-target and target metabolomics technology. Results The clinical response rate for BL-99_high [43 (95.6%) of 45] group was significantly higher than that for placebo [28 (62.2%) of 45, P = 0.001], BL-99_low [36 (76.6%) of 47, P = 0.019] or positive control group [34 (70.8%) of 48, P = 0.006] after an 8-week treatment. In particular, BL-99_high group was still higher than that for placebo or positive control group after 2-week follow-up and 6-week questionnaire survey periods. Further metagenomic and metabolomics studies found that PPI significantly decreased the gut microbiota diversity, induced the cluster of Escherichia enterotype and decreased butyrate contents. Interestingly, BL-99 converted the gut microbiota enterotype from Bacteroidetes ( Alistipes finegoldii , Alistipes shahii ) to Firmicutes c ( Roseburia intestinalis , Roseburia inulinivorans ) and Escherichia enterotype was not clustered after 8-week treatment, which activates carbohydrate esterase activity, and increases faecal and serum butyrate levels. Conclusion BL-99 sustainably alleviated FD symptoms by altering the taxonomic composition and functional potential of the FD microbiome. Trial registration Chictr.org.cn ChiCTR2000041430.