TBA (16S114)

Gut permeability and inflammation in irritable bowel syndrome and inflammatory bowel disease: implications for pregnancy complications

Author(s)

Sabra Z 1,2,3, Kennedy PJ 3, 4, Cryan JF 3,5, Dinan TG 3,4, Quigley EMM 3,6, Khashan AS 1, 2, Kenny LC 1, Clarke G 3, 4

Department(s)/Institutions

1 Irish Centre for Fetal and Neonatal Translational Research (INFANT), Department of Obstetrics and Gynaecology, Cork, Ireland. 2 Department of Epidemiology and Public Health, University College Cork, Cork, Ireland. 3 APC Microbiome Institute, University College Cork, Cork, Ireland 4 Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland 5 Department of Anatomy and Neuroscience 6 Lynda K and David M Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital, 6550 Fannin St, SM 1001, Houston, TX 77030, USA.

Introduction

Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) are gastrointestinal disorders that are very prevalent in women of reproductive age. Both conditions are associated with an increased risk for adverse outcomes from pregnancy but the biological basis of this risk is poorly understood.

Aims/Background

This study is based on the hypothesis that IBD subjects who are in remission and IBS may share a common deficit in intestinal permeability leading to chronic low grade inflammation which may have implications for pregnancy complications. This hypothesis was assessed using lipopolysaccharide-binding protein (LBP) as a circulating marker of intestinal permeability. The pro-inflammatory consequences of any increase in intestinal permeability was determined by assessing cytokine levels. We also assessed the impact of these biological features on the availability of tryptophan, a precursor to a number of neuroactive agents whose metabolism is immunoresponsive.

Method

This study was conducted on 29 healthy females (control), 33 IBS patients, and 16 IBD patients in remission, matched on the basis of age. Plasma levels of LBP were assayed in duplicate using a commercially available immunoassay. Plasma levels of IL-8 were measured using an electrochemiluminescence-based assay. Tryptophan and kynurenine pathway metabolites were measured using high performance liquid chromatography (HPLC).

Results

LBP was significantly elevated in IBD patients compared to controls (p<0.05). This was associated with increased concentrations of TNF-a (p<0.05) and altered tryptophan metabolism (p<0.001). Although not significantly different from controls, IBS subjects displayed an intermediate physiological signature between healthy controls and IBD.

Conclusions

Women with IBD in remission and IBS share a graded biological scar indicative of increased gut permeability and an associated pro-inflammatory profile that impacts on tryptophan metabolism. This may have implications for the mechanism underpinning the pregnancy complications associated with both gastrointestinal disorders but it is currently unknown whether these biological features are further exacerbated during gestation. Future studies are thus required to understand how these biomarkers alter during pregnancy and the associated implications for fetal neurodevelopment.