CHICAGO — Probiotics modulated brain activity in people with irritable bowel syndrome (IBS), and these changes were associated with symptom improvement in a small, randomized controlled trial comparing probiotics with placebo. 

“Most mechanistic studies on probiotics have focused on the gut-level changes, especially on the microbiota, the barrier function, and so on. By contrast, much less is known about whether probiotics can modulate the central nervous system,” said Tao Bai, MD, a gastroenterologist at Huazhong University of Science and Technology, Tongji Medical College Union Hospital in Wuhan, Hubei, China. 

The current study adds to what is known about probiotics in IBS by “providing direct neurobiological evidence for the probiotic's mechanism of action via the brain-gut axis,” Bai said here at Digestive Disease Week (DDW) 2026. 

Although people with IBS often take probiotics, little is known about the potential effect of changing the gut microbiota on brain function and structure. 

The heterogeneity of IBS in clinical practice and the heavy reliance on patient self-reports to guide diagnosis and treatment are additional challenges, Bai said. There is a need for more objective measures, he added. 

Study Methodology 

To learn more, researchers randomly assigned 33 eligible participants with Rome III IBS to 4 weeks of bifidobacterium quadruple viable tablets and 33 others to placebo. A third group of 38 healthy controls without IBS were matched for age, sex, and BMI. 

Bai and colleagues imaged the brain before and after the intervention in both groups. All participants had multimodal 3-Tesla magnetic resonance imaging (Philips Ingenia CX) at baseline and at study completion. Resting-state functional MRI (rs-fMRI) metrics including amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and diffusion kurtosis imaging (DKI) metrics were obtained. 

Study investigators also measured serum metabolite changes, assessed fecal samples, and asked participants about improvements in symptoms of IBS and any anxiety or depression. 

“In addition to IBS symptoms, many patients have psychological comorbidities such as anxiety and depression, which substantially reduce the quality of life and increase the healthcare burden,” Bai said.

Clinical assessments included the IBS-Severity Scoring System (IBS-SSS), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7).

It Is Brain Science

Previous imaging studies have shown that several brain regions, particularly the insula and the medial prefrontal cortex, are relevant in IBS. In addition, the abnormal organization of the large-scale functional brain networks has also been described, Bai said. 

In addition, the researchers integrated multimodal MRI data with gut microbiome and plasma metabolomics data to investigate the potential mechanism by which probiotics influence brain structure and function changes.

The rs-fMRI revealed that the probiotics induced significant neuromodulation. There was a normalization effect, where pathologically elevated ReHo in regions like the right cuneus and supramarginal gyrus was reduced toward levels in healthy controls (all P < .05). There was also an independent modulation effect associated with specific ALFF decreases in the right amygdala and ReHo increases in the bilateral pallidum in regions without baseline abnormalities (all P < .05).

DKI analysis revealed microstructural alterations. These changes included normalization of axial kurtosis in the bilateral pallidum and decreased fractional anisotropy and kurtosis fractional anisotropy in the left cuneus, which were significantly different from placebo (P < .05). The assessment also showed complex remodeling in temporal regions. 

Clinical Improvements

Clinically, the probiotics group achieved significantly higher IBS-SSS response rates at 66.7% compared to 42.4% with placebo (P = .048). However, changes in GAD-7 and PHQ-9 scores were not significantly different between groups over the 4-week period. 

The observed neuroimaging changes correlated with symptom improvement. For example, reductions in pallidal and cuneus ReHo were associated with improvements in IBS-SSS and anxiety scores (P < .05). At the same time, placebo-treated patients showed positive correlations between insula ALFF increases and symptom worsening (P < .05).

A meeting attendee asked how Bai and colleagues selected the probiotics. The choice of probiotics was based on their previous work that demonstrated short-term efficacy of a specific combination of bifidobacterium probiotics in diarrhea-predominant IBS. 

More Research Needed

“Tao Bai presented a double-blind, randomized, controlled trial of a quadruple bifidobacterium probiotic in IBS, in which there was a better global response compared with placebo,” DDW session co-moderator Heidi Staudacher, PhD, an advanced accredited practicing dietitian and researcher specializing in the gut-brain axis at Monash University in Melbourne, Australia, said when asked to comment. 

Interestingly, it also examined potential mechanisms underlying response and is one of the few studies to do so, Staudacher said. The results showed “normalization of regional brain activity in the probiotic group, which was associated with symptom improvement.” 

“This points toward potential neurobiological effects of this specific probiotic,” she added. 

Staudacher noted the study size was modest with 72 participants. For this reason, she said, further studies are warranted to confirm the findings.

The study was supported by Hangzhou Grand Biologic Pharmaceutical Inc. Bai and Staudacher had no relevant financial disclosures.

Damian McNamara is a freelance contributor to Medscape Medical News. He worked full-time for Medscape and WebMD from 2018 to 2024. Damian has a BA in chemistry and an MA in science, health, and environmental reporting/journalism.