Impact of probiotics
In reviewing key research, Dr. Mayer also pointed to interventional studies that support bidirectional relationships between the brain and the gut microbiome.
Studies of gut microbiome-targeted therapies in patients with IBS have shown mixed results – both positive and negative findings – and have been of variable quality. However, a couple of well-done small studies “have shown that probiotics can modulate brain activity and affect psychiatric symptoms,” Dr. Mayer said.
One of these studies, a randomized, double-blind placebo-controlled study of 44 adults with IBS, found reductions in depression scores and changes in brain activation patterns in those who took the probiotic Bifidobacterium longum.
Studies in healthy women are also telling. One of his team’s studies looked at the impact of 4 weeks of a fermented milk product with a 5-strain probiotic consortium on brain intrinsic connectivity and responses to emotional attention tasks.
“We saw significant changes in the connectivity of multiple brain regions ... networks related to emotional regulation circuits within the brain,” he said. “We have to assume that the perturbation happened at the gut-microbiome level.”
A study from Germany demonstrated that the probiotic Bifidobacterium longum modulated brain activity of healthy individuals during social stress.
Impact of cognitive-behavioral therapy
Emanating from the brain, nonpharmaceutical brain-targeted therapies have been shown to reduce IBS symptom severity, he said. In one randomized controlled trial of more than 400 patients with refractory IBS, a primarily home-based version of cognitive behavioral therapy (CBT) produced significant and sustained improvement in symptoms compared with education.
And a study published last year by Dr. Mayer and coinvestigators demonstrated that a positive clinical response to CBT was associated with changes in both the brain (changes in functional and structural connectivity) and the gut microbiota.
Eighty-four IBS patients underwent multimodal brain imaging and psychological assessments before and after CBT, and 34 of the participants underwent microbiome assessments with 16S rRNA A gene sequencing, untargeted metabolomics, and measurement of short-chain fatty acid from fecal samples collected at baseline and post treatment.
In comparing responders (58) and nonresponders (26), the researchers found that response to CBT could be predicted from baseline microbiota composition (including increased Clostridiales and decreased Bacteroides), and that responders had microbial shifts after therapy – including expansion of Bacteroides – in addition to distinct brain changes. “We know which brain networks [in patients with IBS] are sensitive to CBT,” said Dr. Mayer.
Eugene B. Chang, MD, the Martin Boyer Distinguished Professor of Medicine at the University of Chicago and director of the university’s Microbiome Medicine Program, said in an interview after the meeting that the brain-gut-microbiome system “is a very important area for investigation” not only for IBS but for hepatic encephalopathy and other problems and disorders such as neurodegenerative disorders (e.g., Alzheimer’s and Parkinson’s) and circadian disruption, “where gut dysbiosis has been implicated as causative or contributory.”
The specialty still has very little understanding of IBS, and “clinical practice remains largely empirical,” he said, noting that his program is embarking on studies of the brain-gut microbiome system.
Dr. Mayer reported that he serves on the advisory board of Axial Biotherapeutics, Pendulum, Bloom Science, and several other companies. Dr. Chang reported that he has no relevant disclosures.