Therapeutic Modulation of the Gut Microbiome by Supplementation with Probiotics (SCI Microbiome Mix) in Adults with Functional Bowel Disorders: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Functional bowel disorders (FBDs) are chronic gastrointestinal conditions characterized by recurrent symptoms associated with gut microbiota dysbiosis. Although accumulating evidence suggests that probiotics can improve symptoms in patients with FBD, the underlying mechanisms remain to be fully elucidated. In this randomized, double-blind, placebo-controlled clinical trial, 38 adults meeting the Rome IV diagnostic criteria of functional constipation (FC) and functional diarrhea (FD) received either a multi-strain probiotic complex or placebo for 8 weeks. Clinical outcomes were evaluated using the Irritable Bowel Syndrome Severity Scoring System (IBS-SSS), bowel habits questionnaire, and IBS Quality of Life (IBS-QoL) instrument. Fecal samples were collected at baseline and at week 8 for gut microbiota profiling via 16S rRNA gene sequencing and metabolomic analysis using gas chromatography-mass spectrometry. Probiotic supplementation significantly reduced the severity of abdominal bloating and its interference with quality of life, and improved the body image domain of the IBS-QoL. Beta diversity analysis showed significant temporal shifts in the probiotic group, while 16S rRNA sequencing revealed an increased relative abundance of Faecalibacterium prausnitzii and Blautia stercoris. Fecal metabolomic analysis further indicated elevated levels of metabolites implicated in the gut-brain axis. Multi-strain probiotic supplementation alleviated gastrointestinal symptoms and improved aspects of psychosocial well-being in adults with FBDs, potentially through modulation of the human gut microbiome.

Keywords: Blautia stercoris; Faecalibacterium prausnitzii; clinical trial; functional bowel disorders; human gut microbiome; probiotics; serotonin.

Figure 1

Flow diagram of participant progression through the study. Thirty-nine individuals were screened for eligibility; 1 was excluded due to withdrawal of consent, and 38 participants were randomized into probiotic and placebo groups. During the study, nine participants discontinued for reasons including prohibited medication use and protocol deviations. A total of 15 participants in the probiotic group and 14 in the placebo group completed the trial and were included in the per-protocol analysis. n refers to the sample size.

Figure 2

Improvements in gastrointestinal symptoms and quality of life in the probiotic group during the 8-week intervention. (A) Interference with quality of life and (B) abdominal bloating severity were measured using the IBS-SSS, whereas (C) the body image domain score was derived from the IBS-QOL. Data are presented as mean ± SD at baseline, week 4, and week 8. Significant differences between the probiotic and placebo groups are indicated (* p < 0.05; Mann–Whitney U test).

Figure 3

Gut microbiota diversity dynamics in placebo and probiotic groups over time. (A) Alpha diversity indices (Chao1, Shannon, Simpson) remained stable across groups. Panels correspond to week 0, 4, and 8 (top to bottom). (B) Beta diversity was visualized using Non-metric Multidimensional Scaling plots based on Bray–Curtis dissimilarity. Each point represents the microbial community of an individual participant; closer points indicate higher similarity. Plots correspond to week 0, 4, and 8 (left to right), with temporal clustering observed in the probiotic group, reflecting changes in microbial composition.

Figure 4

Species-level comparison of gut microbiota between placebo and probiotic groups. Box plots illustrate significantly different species abundances at week 4 and week 8. Blautia stercoris and F. prausnitzii were notably increased in the probiotic group, suggesting enhanced anti-inflammatory potential (* p < 0.05; Mann–Whitney U test).

Figure 5

Distinct fecal metabolomic signatures between placebo and probiotic groups. (A) PCA and (B) PLS-DA showed group separation at weeks 4 and 8. (C) VIP plots identified key discriminatory metabolites. (D) Heatmaps and (E) volcano plots highlighted significantly altered metabolites, with red and blue dots indicating increased and decreased levels in the probiotic group, respectively.

Figure 6

Enrichment of neuroactive and immunomodulatory metabolites in the probiotic group at week 8. Violin plots depict relative abundances of L-alanine, DABA, L-norvaline, nonanoic acid, L(+)-2-aminobutyric acid, and serotonin levels. These metabolites are implicated in gut–brain axis signaling and immune modulation. Significance was determined using the Mann–Whitney U test (* p < 0.05; ** p < 0.01).