Do Nutritional Supplements Targeting the Gut Microbiota Improve IBS Symptoms?

Key Highlights

• Four nutritional supplements did not increase fecal Bifidobacterium abundance or short-chain fatty acid levels compared with placebo.
• Improvements in irritable bowel syndrome (IBS) symptom severity and quality of life were observed within some groups but were not superior to placebo.
• No significant effects were seen on stool frequency, stool consistency, anxiety, or depression scores.
• Findings underscore the challenge of demonstrating microbiota-targeted benefits beyond placebo in IBS.

A randomized, double-blind, placebo-controlled trial published in Journal of Nutritional Science evaluated whether 4 nutritional supplements with hypothesized microbiota-modulating properties could alleviate symptoms of irritable bowel syndrome (IBS), including its subtypes: IBS with constipation, IBS with diarrhea, IBS with mixed bowel habits, and IBS unclassified. The study found no significant benefit of any supplement over placebo for key microbiota or clinical outcomes in adults with IBS.

Irritable bowel syndrome is a prevalent functional gastrointestinal disorder for which patients frequently adopt restrictive diets or over-the-counter supplements to control symptoms. While such strategies may reduce symptom burden, they also carry risks of nutritional inadequacy and inconsistent efficacy, highlighting the need for controlled evidence to guide clinical recommendations.

To fill this gap in knowledge, researchers conducted a 4-week, parallel-group randomized controlled trial in the Netherlands involving 70 adults (69 completed; 58 women, 11 men) aged 18 to 65 years who met Rome IV criteria for IBS. Participants were randomly assigned to receive resistant starch type 4, pea inner fiber, chondroitin sulfate, a cow’s milk–derived protein hydrolysate containing α-casozepine, or placebo (Table 1).

Table 1. Daily dosages of nutritional supplements and placebo evaluated in adults with IBS

The primary outcome was change in relative abundance of fecal Bifidobacterium. Secondary outcomes included fecal microbiota composition, fecal short-chain fatty acid concentrations, IBS symptom severity, stool pattern, quality of life, and anxiety and depression scores. Stool samples and validated questionnaires were collected at baseline and after the intervention.

Study Findings

After 4 weeks, none of the nutritional supplements significantly increased fecal Bifidobacterium abundance compared with placebo. Alpha and beta diversity of the gut microbiota and concentrations of total short-chain fatty acids, including acetate, propionate, and butyrate, also did not differ between groups.

Within-group reductions in IBS Symptom Severity Score were observed with chondroitin sulfate and resistant starch; however, similar improvements occurred in the placebo group, and between-group differences were not significant. Quality-of-life scores improved modestly in the chondroitin sulfate and placebo groups, again without significant differences between interventions.

No significant changes were detected in stool frequency, stool consistency, anxiety, or depression scores across treatment arms. Mild to moderate gastrointestinal adverse events were reported, with no serious adverse events.

Clinical Implications

According to the study authors, the findings suggest that the tested nutritional supplements, at the given dosages and duration, do not provide measurable benefits over placebo for microbiota modulation or symptom improvement in IBS. The results highlight the substantial placebo response observed in IBS trials and the complexity of targeting the gut microbiome in this population.

This study had limitations. For example, the authors acknowledged that high placebo responsiveness in IBS, along with substantial inter-individual variability in symptoms and baseline microbiome composition, may have limited the detection of treatment effects. Relatively high baseline Bifidobacterium levels and heterogeneity across IBS subtypes may have further reduced the potential for measurable change. They also noted that although the study was powered for microbiota outcomes, the sample size may have been insufficient to detect differences in subjective measures, and the authors noted that future studies should incorporate larger cohorts, subtype stratification, a run-in period, positive controls, and potentially higher supplement dosages.

Expert Commentary

“We conclude that the nutritional supplements, at the dosages tested in the current study, were not able to increase the relative abundance of Bifidobacterium in subjects with IBS within a 4-week intervention,” the researchers concluded.

Reference
van den Belt M, Liu Z, Janssen Duijghuijsen L, et al. Randomised controlled trial: nutritional supplements to relieve irritable bowel syndrome symptoms by targeting the gut microbiota. J Nutr Sci. 2025;14:e46. doi:10.1017/jns.2025.10021