Increasing scientific data confirm that what have been called functional gastrointestinal (GI) disorders are in fact disturbances in the bidirectional interaction between the brain and the gut, according to a panel of experts at the American College of Gastroenterology (ACG) 2020 Virtual clinical meeting and postgraduate course.

Lin Chang, MD, FACG, from the David Geffen School of Medicine at the University of California at Los Angeles, explained that these disorders of the brain-gut interaction are “classified by GI systems related to any combination of motility disturbances, visceral hypersensitivity, altered mucosal and immune function, altered gut microbiota, and altered central nervous system (CNS) processing.” Such disorders include irritable bowel syndrome (IBS), chronic constipation, and functional dyspepsia, among others.

Evidence indicates that brain networks are altered functionally and structurally in patients with IBS. “Gut microbiota can communicate to the brain directly,” Dr Chang explained. “Disruptions can influence the communication between the gut and brain and contribute to pathogenesis of IBS, autism, anxiety, attention deficit-hyperactivity disorder, and obesity.”

Studies of the gut microbiome in IBS show reductions in types of microbiota that can reduce GI symptoms and depression, maintain gut health, and have anti-inflammatory effects. In contrast, the microbiome in IBS may have higher levels of organisms that produce toxins or reduce mucosal glycoproteins.

In a systems views, Dr Chang explained, stresses in the gut caused by diet, antibiotics, infections, and psychosocial stress on the brain, can alter the interaction between the brain connectome and gut connectome to create GI symptoms.

Therapies that can affect the brain-gut interactions include cognitive behavioral therapy, hypnotherapy, mindfulness meditation, and neuromodulators. Diet, antibiotics, and probiotics, among other options, also can target conditions in the gut.

Brian Lacy, MD, FACG, professor of medicine at Mayo Clinic-Jacksonville, noted that among patients with IBS, the pathophysiology of abdominal pain can be affected by the gut microbiome, certain genetic predispositions, immune activation, alterations in gut motility and permeability, and stress. “All of these combined can lead to the development of visceral hypersensitivity.”

Dr Lacy observed, “Pain is a modifiable experience. It’s felt and interpreted differently in different patients.” Genetics, cognitive factors, mood, psychosocial factors, chemical, and structural factors may all play a role.

A number of therapeutic options are available, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and atypical agents, which in GI practice are all considered neuromodulators.  “Many of these therapeutics have positive monoaminergic effects on the brain” that can improve pain-related brain circuits and mood.

Dr Lacy noted that these therapies have long track records of safety and success, including in some pain syndromes such as fibromyalgia, chronic headache, and diabetic neuropathy. These drugs are easily titrated in the clinic, and are very cost-effective.

Dr Lacy noted that he usually starts TCAs at a lower dose and titrates up as needed. A study in which he participated showed these therapies are quite effective in controlling pain. “I believe tricyclics should be considered first-line therapy for treating pain in patients with IBS and other painful functional GI disorders.”

All tricyclics are helpful in reducing diarrhea, he stated. While SSRIs are good for treatment of anxiety, phobias, and psychological distress, they are not generally helpful for control of pain.

However, SNRIs are effective in treating chronic pain. “We do not have large randomized placebo-controlled studies at present, but I think they are very reasonable course of action for treatment of chronic abdominal pain,” Dr Lacy stated. These therapeutics generally have fewer side effects than TCAs.

William Chey, MD, FACS, Nostrant Collegiate Professor and director of the Nutrition & Behavioral Medicine Program at the University of Michigan, discussed the role of diet in treating disorders of the brain-gut interaction, with a particular focus on IBS.

Dr Chey noted that patients who report wheat or gluten sensitivity look much like patients with IBS or functional dyspepsia, reporting very similar symptoms. Based on a meta-analysis of a gluten-free diet for IBS, “there is currently insufficient evidence to recommend a gluten-free diet for IBS symptoms.” However, he added, “we cannot exclude the possibility of a benefit and clearly, more research is needed.” Some research suggests that some patients with IBS may have atypical non-IgE-mediated food allergies, including allergies to wheat.

Fermentable oligo-, di- and monosaccharides and polyols (FODMAPs) are short-chain carbohydrates that the small intestine may have difficulty digesting, Dr Chey explained. “There are many foods in the Western diet that contain FODMAPs,” which can produce gas. Dr Chey and colleagues identified 7 trials that found the low FODMAP diet “was more likely to lead to a significant reduction in overall IBS symptoms” that other diets used for comparison.

Dr Chey and colleagues at University of Michigan conducted a comparison study of low FODMAP and the m-NICE Diet, and found significant improvements in quality of life for patients on the low FODMAP diet. “There was also a more than 2-fold increased likelihood benefit with the low FODMAP diet rather than the usual dietary recommendations for IBS.”

For a patient who is hesitant to pursue dietary therapy, Dr Chey said, “Don’t try to force it. It will be a waste of everybody’s time.”

What is effective, Dr Chey said, is an integrated care approach that involves the gastroenterologist, a registered dietitian, and behavioral therapist working together with the patient with IBS. “IBS treatment has to be multidisciplinary, it has to be holistic in approach.” One study revealed that 84% of patients who received integrated care showed significant improvement in symptoms of IBS compared with 57% of those who received usual standard of care.

Laurie Keefer, PhD, professor of medicine in psychiatry at the Icahn School of Medicine at Mount Sinai in New York, addressed the importance of psychological care for patients with IBS and other disorders of the gut-brain axis. She focused on positive psychology, which is “the study of how people thrive despite obstacles.” Positive psychology interventions can be delivered at the time of diagnosis, to help stave off depression and anxiety during the course of the disease.

Resilience—the ability to bounce back from negative circumstances—can be significantly lower among patients with IBS, but as one study revealed, patients with higher resilience had lower IBS symptom severity.

Gastroenterologists and their staffs can help patients develop a more positive outlook by discussing such factors as the patient’s social support structures, what they do that they enjoy, positive emotions the patient has recently experienced, diet and sleep patterns, and energy and activity levels.

Dr Keefer also encouraged practitioners to work with their patients on practicing gratitude, coaching on mindfulness and self-compassion, and encouraging the creation of strong social supports, which have significant positive effects on health.

“A well-being review of systems is a helpful way to start the conversation around patient goals and expectations,” she explained. “Gastroenterology practices can create a culture of well-being and resilience by focusing on programming that builds optimism, positive emotions, and social support for patients and their providers.”

--Rebecca Mashaw

Chang L. Brain-Gut Axis and Its Interaction with the Enteric Microbiome. Chey, WD. Dietary and CAM Approaches for the Management of IBS. Keefer, LA. Positive Psychology Interventions for Functional GI Disorders. Lacy, BE. A Practical Approach to the Use of Antidepressants for Functional GI Disorders. Talks presented at: American College of Gastroenterology Clinical Meeting and Postgraduate Course. October 25, 2020. Virtual.