Associations among gut permeability, inflammatory markers, and symptoms in patients with irritable bowel syndrome - PubMed (original) (raw)

Associations among gut permeability, inflammatory markers, and symptoms in patients with irritable bowel syndrome

Robert J Shulman et al. J Gastroenterol. 2014 Nov.

Abstract

Background: Alterations in gastrointestinal (GI) permeability and immune measures are present in some patients with irritable bowel syndrome (IBS) but the relationship to symptoms is poorly defined. In adults with IBS, we compared permeability, unstimulated peripheral blood monocyte (PBMC) interleukin-10 (IL-10) levels, IBS life interference, and GI and psychological distress symptoms.

Methods: In 88 women and 18 men with IBS, GI permeability was quantitated as percent recovery of urinary sucrose and the lactulose/mannitol (L/M) ratio. IL-10 was measured in supernatants from 72-h incubated, unstimulated PBMCs. Participants completed a 4-week daily diary recording IBS life interference on daily activities and work, IBS symptoms, and psychological distress symptoms. They also completed the Brief Symptom Inventory.

Results: The L/M ratio but not percent sucrose recovery was significantly correlated with IBS interference with activities and work and retrospectively measured anxiety and depression. Unstimulated PBMC production of IL-10 correlated significantly with IBS interference with daily work, IBS symptom score, and abdominal pain. We identified a subgroup of IBS subjects with higher IL-10 and/or higher L/M ratio who had substantially higher IBS interference and IBS symptom scores.

Conclusions: Our findings suggest a distinct subgroup of IBS patients with alterations in gut barrier function. This subgroup is characterized by increased GI permeability and/or increased PBMC production of IL-10. These physiologic alterations reflect more severe IBS as measured by interference of IBS with daily activities and daily IBS symptoms.

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Figures

Figure 1

Figure 1

Scatterplots showing the relationship between IBS interference (percent of days on a 28 day daily diary when symptoms interfered with activities) and: gut permeability as measured by lactulose/mannitol ratio (Left Panel); production of IL-10 by non-stimulated peripheral blood mononuclear cells incubated for 72 hours (Right Panel). The vertical lines at 0.015 in A and at 250 pg/ml in B were chosen to be approximately in the middle of the transition from low to high mean IBS interference. Tables 2 and 3 are based on these thresholds.

Figure 2

Figure 2

Scatterplots showing the joint relationship of IL-10 production by incubated peripheral blood mononuclear cell (PBMC) and lactulose/mannitol ratio to clinical measures shown as colored symbols indicating: IBS interference (percent of days on a 28 day daily diary when symptoms interfered with activities) (Left Panel); Composite IBS symptom score defined by averaging the percent of days with each of the symptoms: abdominal pain or discomfort, abdominal pain or discomfort up to 2 hours after eating, abdominal distension, bloating, intestinal gas, constipation, diarrhea, and urgency (Right Panel). Subjects with low interference and low IBS symptom score predominate in the lower left corner of these plots, while subjects with higher IBS interference and higher IBS symptom score predominate in the rest of the plot, among those with either higher IL-10 or higher L/M ratio. See Table 4 for additional related results.

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