COVID-19: Irritable bowel syndrome (IBS) have a connection to psychosocial factors


Patients’ irritable bowel syndrome (IBS) symptoms unexpectedly improved when they were under COVID-19 stay-at-home orders, reaffirming the gut-brain connection in functional gastrointestinal disorders, according to research that was selected for presentation at Digestive Disease Week (DDW) 2021.

“One of our main hypotheses was that these patients were going to be worse because of pressure and stress due to COVID-19,” said Juan Pablo Stefanolo, MD, a lead author on the study and a physician with the Neurogastroenterology and Motility section, Hospital de Clínicas José de San Martín, Buenos Aires University, Argentina.

“We think the results have something to do with people staying at home. They were not exposed to outside stress, and at home they were able to avoid food triggers.”

Pandemic lockdown orders in Argentina created a unique opportunity for researchers to study the impact of pandemic stressors and reduced social interaction on 129 IBS patients whose pre-pandemic data had already been collected through an earlier research project.

The patients were re-assessed during the lockdown with the same online survey that included multiple validated measures of IBS severity, anxiety and depression, along with questions about co-occurring illnesses, including heartburn, regurgitation, indigestion, chronic fatigue, fibromyalgia and nonmigraine headaches.

During the lockdown in Argentina – one of the longest lockdowns in the world—the number of patients experiencing severe IBS fell sharply from 65 to 39.

The mean Irritable Bowel Syndrome Severity Scale score for the group also fell 66 points, from 278 to 212 on a 500-point scale. IBS symptoms of pain, distention, stool consistency, anxiety, somatization, fibromyalgia and chronic fatigue symptoms all improved during the lockdown.

Patients with functional gastrointestinal disorders experience symptoms even though no structural or biochemical abnormalities are present. The gut-brain connection refers to the role of stress and psychological difficulties in triggering debilitating gut-related symptoms.

Headache, heartburn and regurgitation – all outside the category of functional disorders—became worse during the study, likely due to the increase in weight that nearly 60 percent of patients reported.

“Our results reinforce the concept that IBS, or functional gastrointestinal disorders, have a connection to psychosocial factors, as well as food and other factors,” Dr. Stefanolo said. “The gut-brain axis has a lot of facets.”

Irritable bowel syndrome (IBS) is a common disease with a high incidence rate that imposes enormous burdens on healthcare systems.1 According to the predominant stool form and bowel habits of patients there are four heterogeneous clinical phenotypes of IBS: diarrhea-predominant IBS (IBS-D), constipation-predominant IBS (IBS-C), mixed IBS and unclassifiable IBS.2 IBS features various symptom combinations including abdominal pain mainly, bloating, and altered stool frequency, in the absence of any detectable organic disease or available clinical tests and examinations.3

It has been reported that the worldwide prevalence of IBS is approximately 10–20%.4 The pathogenesis of IBS is unclear so far, however, multifactorial factors such as genetics, dietary intolerance, alterations in the gastrointestinal (GI) microbiota, visceral hypersensitivity, increased intestinal permeability, small intestinal overgrowth (SIBO), intestinal immune activation, disruption of the gut-brain axis, abnormal pain processing, behavioral pathways, and altered GI motility have been reported.5,6

Comorbidity of IBS and psychological disorders is known to be widespread. According to US statistics, 47% of patients with IBS have a variety of common mental diseases, including major depression, generalized anxiety disorder, panic disorder, somatization disorder and post-traumatic stress disorder, etc.7

Studies also confirmed that psychological stress can increase the visceral sensitivity in the gastrointestinal tract, thus playing an important role in the onset of functional gastrointestinal diseases such as IBS.8 What’s more, other researches further revealed that mental anxiety and depression, which may be regulated by some major tyrosine peptides, such as Neuropeptide Y (NPY),9 were closely associated with the onset of IBS-D and can be an effective target for its treatment.10 In fact antidepressants, antianxiety drugs, and some other psychotherapy (non-drug therapy) do exert exact effects on IBS to a certain extent.11

Neuropeptide S (NPS), a 20 amino acid peptide, which is highly conserved among mammals, works by binding to the NPS receptor selectively.12 The activation of the NPS system can lead to relief of anxiety.13 Another neuropeptide, NPY, as a 36-residue amidated peptide, is simultaneously existed in the central and peripheral nervous systems.14

Combining with the receptor, the NPY system can control memory retention, energy homeostasis, sleep regulation, regulation of food intake and vasoconstriction. Applied for the development of various kinds of agonists and antagonists, it plays a critical role in treating diseases such as epilepsy, neurodegenerative disorders, obesity, and psychiatric disorders.15

Protease-activated receptor 2 (PAR-2), also called trypsin receptor 1, belongs to a family of four G protein-coupled receptors, which is reported to be connected with visceral pain in the colon and results in increased recruitment of inflammatory cells, including mast cell (MC).16,17

Inflammatory molecules secreted by those activated cells, such as histamine and proteases, increase the synthesis of inflammatory mediators by MC, which promote visceral hypersensitivity in patients with IBS-D.18 Abnormal activation of PAR-2 by colonic MC, in turn, appears to induce visceral hypersensitivity in patients with IBS-D as well.

So far accumulated pieces of evidence have indicated that IBS pathophysiology has been linked to life stress, epithelial barrier dysfunction, and MC activation.19 Yet the role of mediators of stress responses in the gastrointestinal tract on IBS mucosal function remains largely unknown.

Therefore, we hypothesize that there might be a linked relationship between MC, PAR-2 and neuropeptide, which could cause relevant clinical symptoms and psychological negative changes in IBS patients.

This trial selected IBS-D patients, with the assessment of depression and anxiety, measuring the expression level of NPS, NPY, PAR-2, NPY2R, exploring the correlation of psychological stress, MC, PAR-2 and brain intestinal peptide in the occurrence and development of IBS, actively investigating representative and effective indicators for pathophysiology and clinical treatment of IBS.

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More information: Dr. Stefanolo will present data from the study, “Gut-brain axis and irritable bowel syndrome during SARS-CoV-2 pandemic. A survey-based study,” abstract Su093, on Sunday, May 23, at 1 p.m. EDT.


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