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The view of irritable bowel syndrome (IBS) as a disorder of altered interactions within the brain-gut-microbiome system is supported today by “extensive clinical, brain and microbiome-derived evidence,” Emeran A. Mayer, MD, of the University of California, Los Angeles, said at the annual Gut Microbiota for Health World Summit.
A recently published genome-wide analysis from the United Kingdom of more than 53,000 people with IBS found shared genetic pathways with mood and anxiety disorders and “is one of the most convincing studies to date [showing] that we’re not dealing with separate disorders, but that we’re dealing with the brain-gut-microbiome system,” said Dr. Mayer, director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience, and codirector of the Cure: Digestive Diseases Research Center at UCLA.
Meanwhile, multi-omics analyses from his team have established significant differences in the composition and function of the gut microbiome between IBS and healthy controls and, significantly, between IBS subgroups, he reported.
The genome analysis, published in Nature Genetics, utilized the UK Biobank, which contains genome-wide SNP genotyping data and health data for a half a million individuals. People with IBS were identified with a digestive health questionnaire that included Rome III symptom criteria.
In their cohort of 53,400 IBS cases and 433,201 healthy controls, the researchers identified 6 genetic susceptibility loci for IBS, 3 of which have previously been shown to be associated with depression, neuroticism, and other psychiatric disorders. (Significant associations were replicated in a 23andMe panel.) “The study emphasizes that GI symptoms [of IBS] and mood and anxiety disorders are two sides of the same coin,” Dr. Mayer said.
Differences in IBS subtypes
The team’s multi-omics profiles of the intestinal microbiota in IBS and its subtypes, based on bowel habits, have shown that IBS is characterized by “altered abundances of certain bacterial taxa, transcripts, and metabolites,” he said.
The research, awaiting publication, has also shown that IBS metabolites, transcripts, and transcript/gene ratios differentiate IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C) with high accuracy. In addition, the IBS-D subtype is differentiated from IBS-C by “diverse functional shifts including increased polyamines, bile acids, glutamate synthesis, and ethanolamine utilization,” Dr. Mayer said.
In related multi-omics research incorporating brain imaging data, Dr. Mayer’s team has identified greater alterations in measures of brain connectivity in the IBS-D group, “just as we saw for the microbiome parameters as well,” he said at the meeting, which was sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology & Motility.
These “are all associations,” he noted. The microbiome is an established integral player in gut-brain communication, but “a casual role between the gut microbiome and IBS remains to be established.”
Although mechanistic studies are still in earlier stages, it’s clear that the microbiome is a potentially important site for therapeutic interventions. “Microbiome-targeted therapies are likely to be effective in subsets of IBS patients, based on their bowel habits, and on microbiome features,” said Dr. Mayer.
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.
The view of irritable bowel syndrome (IBS) as a disorder of altered interactions within the brain-gut-microbiome system is supported today by “extensive clinical, brain and microbiome-derived evidence,” Emeran A. Mayer, MD, of the University of California, Los Angeles, said at the annual Gut Microbiota for Health World Summit.
A recently published genome-wide analysis from the United Kingdom of more than 53,000 people with IBS found shared genetic pathways with mood and anxiety disorders and “is one of the most convincing studies to date [showing] that we’re not dealing with separate disorders, but that we’re dealing with the brain-gut-microbiome system,” said Dr. Mayer, director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience, and codirector of the Cure: Digestive Diseases Research Center at UCLA.
Meanwhile, multi-omics analyses from his team have established significant differences in the composition and function of the gut microbiome between IBS and healthy controls and, significantly, between IBS subgroups, he reported.
The genome analysis, published in Nature Genetics, utilized the UK Biobank, which contains genome-wide SNP genotyping data and health data for a half a million individuals. People with IBS were identified with a digestive health questionnaire that included Rome III symptom criteria.
In their cohort of 53,400 IBS cases and 433,201 healthy controls, the researchers identified 6 genetic susceptibility loci for IBS, 3 of which have previously been shown to be associated with depression, neuroticism, and other psychiatric disorders. (Significant associations were replicated in a 23andMe panel.) “The study emphasizes that GI symptoms [of IBS] and mood and anxiety disorders are two sides of the same coin,” Dr. Mayer said.
Differences in IBS subtypes
The team’s multi-omics profiles of the intestinal microbiota in IBS and its subtypes, based on bowel habits, have shown that IBS is characterized by “altered abundances of certain bacterial taxa, transcripts, and metabolites,” he said.
The research, awaiting publication, has also shown that IBS metabolites, transcripts, and transcript/gene ratios differentiate IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C) with high accuracy. In addition, the IBS-D subtype is differentiated from IBS-C by “diverse functional shifts including increased polyamines, bile acids, glutamate synthesis, and ethanolamine utilization,” Dr. Mayer said.
In related multi-omics research incorporating brain imaging data, Dr. Mayer’s team has identified greater alterations in measures of brain connectivity in the IBS-D group, “just as we saw for the microbiome parameters as well,” he said at the meeting, which was sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology & Motility.
These “are all associations,” he noted. The microbiome is an established integral player in gut-brain communication, but “a casual role between the gut microbiome and IBS remains to be established.”
Although mechanistic studies are still in earlier stages, it’s clear that the microbiome is a potentially important site for therapeutic interventions. “Microbiome-targeted therapies are likely to be effective in subsets of IBS patients, based on their bowel habits, and on microbiome features,” said Dr. Mayer.
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.
The view of irritable bowel syndrome (IBS) as a disorder of altered interactions within the brain-gut-microbiome system is supported today by “extensive clinical, brain and microbiome-derived evidence,” Emeran A. Mayer, MD, of the University of California, Los Angeles, said at the annual Gut Microbiota for Health World Summit.
A recently published genome-wide analysis from the United Kingdom of more than 53,000 people with IBS found shared genetic pathways with mood and anxiety disorders and “is one of the most convincing studies to date [showing] that we’re not dealing with separate disorders, but that we’re dealing with the brain-gut-microbiome system,” said Dr. Mayer, director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience, and codirector of the Cure: Digestive Diseases Research Center at UCLA.
Meanwhile, multi-omics analyses from his team have established significant differences in the composition and function of the gut microbiome between IBS and healthy controls and, significantly, between IBS subgroups, he reported.
The genome analysis, published in Nature Genetics, utilized the UK Biobank, which contains genome-wide SNP genotyping data and health data for a half a million individuals. People with IBS were identified with a digestive health questionnaire that included Rome III symptom criteria.
In their cohort of 53,400 IBS cases and 433,201 healthy controls, the researchers identified 6 genetic susceptibility loci for IBS, 3 of which have previously been shown to be associated with depression, neuroticism, and other psychiatric disorders. (Significant associations were replicated in a 23andMe panel.) “The study emphasizes that GI symptoms [of IBS] and mood and anxiety disorders are two sides of the same coin,” Dr. Mayer said.
Differences in IBS subtypes
The team’s multi-omics profiles of the intestinal microbiota in IBS and its subtypes, based on bowel habits, have shown that IBS is characterized by “altered abundances of certain bacterial taxa, transcripts, and metabolites,” he said.
The research, awaiting publication, has also shown that IBS metabolites, transcripts, and transcript/gene ratios differentiate IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C) with high accuracy. In addition, the IBS-D subtype is differentiated from IBS-C by “diverse functional shifts including increased polyamines, bile acids, glutamate synthesis, and ethanolamine utilization,” Dr. Mayer said.
In related multi-omics research incorporating brain imaging data, Dr. Mayer’s team has identified greater alterations in measures of brain connectivity in the IBS-D group, “just as we saw for the microbiome parameters as well,” he said at the meeting, which was sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology & Motility.
These “are all associations,” he noted. The microbiome is an established integral player in gut-brain communication, but “a casual role between the gut microbiome and IBS remains to be established.”
Although mechanistic studies are still in earlier stages, it’s clear that the microbiome is a potentially important site for therapeutic interventions. “Microbiome-targeted therapies are likely to be effective in subsets of IBS patients, based on their bowel habits, and on microbiome features,” said Dr. Mayer.
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.
FROM GMFH 2022