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Irritable bowel syndrome (IBS) is a gut-brain pain disorder that is classified according to bowel habits, even though non-gastrointestinal factors may influence clinical course and outcomes. In light of this discrepancy, Madhusudan Grover, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues conducted a survey-based case-control study to determine if IBS patients cluster according to various parameters, including clinical, dietary, lifestyle, and psychosocial factors. Their findings highlight the importance of recognizing clinical profiles that go beyond GI symptoms in clinical decision making and personalizing treatment for IBS.

Grover outlined the study, which recently appeared in , in the following interview with the Reading Room.

Why did your group feel it was important to look beyond the strictly bowel-related classifications among IBS patients?

Grover: It has been long known and prior studies have also shown that IBS patients have a higher prevalence of certain medical and psychosocial comorbidities, as well as impairment of functioning. More recently, it has been appreciated that IBS patients make significant dietary changes. Our hypothesis was that in a large cohort of IBS patients with detailed clinical metadata, we would identify unique subsets of IBS with variable levels of associations with pain, bowel dysfunction, comorbidities, and diet/lifestyle changes.

How was the study conducted?

Grover: From 2013 to 2020, we drew on the Mayo Clinic Biobank to survey patients and received 40,291 responses to a questionnaire incorporating Rome III criteria for IBS. We determined several factors associated with IBS, and using latent class analysis -- a model-based clustering -- we took a closer look at IBS cases with these in mind.

What was the composition of the study cohort?

Grover: We identified 4,021 older IBS patients with a mean age of 64 years, 75% female, and selected 12,063 non-IBS controls. Of the IBS patients, 1,280 had diarrhea-predominant IBS (32%), 1,021 had constipation-predominant IBS (25%), 1,597 had mixed IBS (40%), and 81 had unsubtyped IBS (2%).

What findings emerged from your analysis?

Grover: Using 26 variables separating cases from controls plus the Rome III variables, we found that the optimal clustering model revealed seven latent IBS clusters demonstrating varying degrees of GI symptoms, comorbidities, and dietary/lifestyle factors. These were characterized by disproportionately higher perceived impairment of health (moderate or severe), higher prevalence of psychoneurological factors (psychoneurological, psychiatric, neurological), and greater bowel dysfunction than the average (diarrhea or constipation predominance).

Health-impairment clusters (representing 33% of the IBS patients), for example, demonstrated more pain, with the severe cluster also entailing more psychiatric comorbidities and non-GI pain -- for example, fibromyalgia. The next three clusters (41% of IBS cases) showed unique enrichment of psychiatric comorbidities such as anxiety and depression, neurological comorbidities such as migraines, or both comorbidities. The cluster with increased psychiatric comorbidities constituted the largest cluster, with 20% of the IBS cases.

The bowel dysfunction clusters -- 24% of the overall IBS cohort -- demonstrated less abdominal pain, with the diarrhea cluster most likely to report pain improvement with defecation. The constipation cluster had the highest score for exercise and the consumption of fruits, vegetables, and alcohol. Patients in both of these clusters had less GI or non-GI pain and other comorbidities.

Interestingly, when we applied Rome IV criteria, the distribution of clusters remained similar. In physiologic tests available for a 6% subset, no significant differences between clusters emerged.

Were any of the findings unexpected?

Grover: We were surprised that a subset of IBS patients with greater bowel dysfunction had a much smaller burden of pain and other comorbidities.

We were also surprised that the subset reporting significant perceived impairment in health and pain only constituted 16% of the overall IBS cohort. This subset had a higher prevalence of psychiatric comorbidities. It was different from a larger cluster of patients with psychological diagnoses but not high scores for pain or impairment in perceived health.

This reflects that pain, both GI and non-GI, likely drives perceived impairment in health more than psychiatric comorbidities. Hence, clinicians should consider these as two unique groups of patients.

Do you foresee these results being integrated into clinical practice?

Grover: We believe these findings set the stage for distinction and appreciation of patients within the larger umbrella of IBS. We hope and anticipate that further studies will test underlying pathophysiology behind these clusters and determine if personalized care would be more beneficial, as well as cost-effective.

Could you sketch a potential scenario in which they might impact the care of an individual patient?

Grover: Multiple potential scenarios emerge from this analysis. It is likely that a subset of IBS patients have much greater bowel dysfunction and not significant pain or psychological comorbidities. Their perceived health impairment is also low. These patients can be targeted with education, reassurance, and peripherally acting therapies.

The clusters with significant neurological issues and migraines should be referred to a neurologist, and similarly those with overlap with fibromyalgia should be considered for co-management with a comprehensive pain management team. Lastly, patients in the severe health impairment cluster will need help from experts in pain management, in addition to centrally acting pharmacological and behavioral therapies.

What still remains to be done?

Grover: Further research is required to assess whether these unique clusters could be used to direct clinical trials and individualize patient management.

You can read the abstract of the study here, and about the clinical implications of the study here.