Autonomic Modulation May Benefit Patients with Constipation-Predominant IBS

New research suggests the potential value of modulating autonomic outflow in patients with constipation-predominant irritable bowel syndrome (IBS-C), highlighting the presence of systemic and local autonomic imbalance in this patient population.1

Findings from the study, coined by investigators as the first to assess both systemic autonomic function and localized intestinal blood flow dynamics in patients with IBS while also accounting for predominant bowel habits and controlling for psychological comorbidity, point to a greater fasting superior mesenteric artery end-diastolic velocity (SMA-EDV) and a lower pulse transit time (PTT) in patients with IBS-C.1

According to the American College of Gastroenterology, IBS affects approximately 10% to 15% of people in the United States. In the absence of a cure, IBS treatment is largely focused on lifestyle modifications relating to diet and stress.2 Pharmacologic options for IBS remain limited, underscoring the importance of research in this area to aid drug development.

“Autonomic dysfunction may contribute to symptom generation in IBS, possibly driven by psychological morbidity and activation of the hypothalamic-pituitary-adrenal axis,” Allison Malcolm, MBBS, a gastroenterologist at Royal North Shore Hospital in Australia, and colleagues wrote.1 “Previous data are conflicting, perhaps due to lack of accounting for differential bowel patterns in IBS or by diverse methodologies used to measure autonomic function.”

To examine differences in systemic autonomic function and intestinal blood flow dynamics in the fasting and postprandial states between IBS subtypes and healthy controls, investigators recruited patients with IBS (n = 20) and healthy controls (n = 20) from the gastroenterology outpatient clinic at a tertiary Australian hospital and through public advertising, respectively. Of note, investigators only included female patients in the present study to eliminate possible gender-associated differences previously suggested in IBS.1

All participants completed the following validated questionnaires: the Center for Epidemiologic Studies Depression Scale (CES-D); the State and Trait Anxiety Inventory (STAI); the Eysenck Personality Questionnaire subscales of neuroticism and extraversion (EPQ); the hypochondriasis subscale of the Illness Behavior Questionnaire (IBQ); and the mature coping style subscale of the Defense Style Questionnaire (DSQ). An additional nonvalidated extraintestinal symptom questionnaire was also administered.1

Among the participants with IBS, the mean age was 35 years, 10 had IBS-C, and 10 had diarrhea-predominant IBS (IBS-D). Investigators noted age and body mass index were well-matched across the IBS and control groups, although they pointed out patients with IBS-C and IBS-D had elevated scores in certain psychological measures and for extraintestinal symptoms.1

In addition to the questionnaires, participants were subject to laboratory testing after an overnight fast, including PTT and US-Doppler blood flow measurements (SMA and aorta). Assessments were conducted concurrently, before and at 10, 20, 30, 40, 60, and 90 minutes after ingestion of the test meal.1

Acknowledging the potential influence of the rate of gastric emptying and food arrival in the small intestine on mesenteric blood flow, investigators also performed gastric emptying studies in the postprandial state. At the end of these tests, a subgroup of patients and controls underwent cold pressor challenges (sympathomimetic) and deep-breathing exercises (parasympathomimetic).1

Compared with healthy controls, SMA-EDV and PTT were lower in patients with IBS-C but not those with IBS-D. Additional regression analyses indicated both SMA-EDV and PTT in IBS-C remained lower relative to controls even after adjusting for most psychological variables. However, investigators noted gastric emptying parameters did not differ between the IBS-C, IBS-D, and matched control groups.1

Further analysis revealed PTT values significantly decreased in all IBS patients and matched controls, with the exception of a nonsignificant decrease observed in a subgroup of IBS-D patients. No difference in PTT postprandial AUC was seen between the IBS-C and IBS-D subgroups and their matched controls, with no changes observed after adjusting for differences in gastric emptying or baseline psychological factors.1

Investigators called attention to a smaller increase in postprandial aortic PSV in patients with IBS-C compared with controls (Coef, −1.13 for comparison of AUCs; 95% CI, –2.05 to −0.21; P = .02), which remained significant after adjusting for the gastric emptying indices as well as various indicators of baseline psychological state. While patients with IBS-C also showed a trend toward a larger increase in SMA-EDV compared to matched controls (Coef, 3.34; 95% CI, –0.42 to 7.09; P = .08), this effect was no longer evident after adjusting for baseline psychological differences.1

All healthy volunteers and IBS patients had a significant reduction in PTT following cold pressor challenge and an increase in PTT following deep breathing exercises. US measurements of SMA blood flow following cold pressor challenge revealed a reduction in SMA diameter and SMA-EDV, the latter of which was significant only in IBS and IBS-C patients. A numerical reduction in SMA-PSV was also observed, although this did not reach statistical significance. Investigators did not observe any differences in the magnitude of changes in all physiology parameters following both challenges between IBS-C or IBS-D and their matched controls.1

“Our findings provide some support for recently suggested therapeutic options modulating autonomic, specifically parasympathetic, outflow, especially in constipation-predominant IBS, yet also provide valuable insight into the likely multifactorial pathophysiology of these bowel-related DGBI,” investigators concluded.1 “Future studies could incorporate pretreatment autonomic function testing for identifying and targeting specific IBS patients more likely to benefit from these treatment modalities.”

References

1. Mazor Y, Leach MM, Jones M, et al. Prospective Evaluation of Autonomic Function and Intestinal Blood Flow in Health and Irritable Bowel Syndrome Shows Differences Limited to Patients With Constipation Predominance. Neurogastroenterology and Motility. https://doi.org/10.1111/nmo.14975
2. American College of Gastroenterology. Irritable Bowel Syndrome (IBS). Accessed December 9, 2024. https://gi.org/topics/irritable-bowel-syndrome/#tabs1