Eugene Campbell

Abnormal Intestinal Permeability in Subgroups of Diarrhea-Predominant Irritable Bowel Syndromes

OBJECTIVES:Irritable bowel syndrome (IBS) is a heterogeneous condition and defined according to symptoms. Low-grade inflammation has been associated with IBS, particularly that following infection, but whether altered intestinal permeability profiles relate to irritable bowel subtype or onset is uncertain. Our aim was to compare small and large intestinal permeability in various subtypes of IBS to healthy controls.METHODS:Intestinal permeability was measured using 1.8 MBq of 51Cr-EDTA and collecting urine over 24 h; Study 1: patients with diarrhea-predominant postinfectious IBS (N = 15), constipation-predominant IBS (N = 15), and healthy controls (N = 15); Study 2: two groups of diarrhea-predominant IBS (D-IBS), one with a history of onset after acute gastroenteritis (postinfectious) (N = 15) and the other without such a history (nonpostinfectious) (N = 15) both compared with healthy controls (N = 12).RESULTS:Permeability expressed as percentage of total dose excreted in urine (median [inter-quartile range]). Study 1: Proximal small intestinal permeability was increased in postinfectious IBS (0.19 [0.12–0.23]) in contrast to constipated IBS (0.085 [0.043–0.13]) and controls (0.07 [0.035–0.19]) (p = 0.02). IBS patients with eczema, asthma, or hayfever had increased proximal small intestinal permeability compared with IBS patients without atopy (p = 0.02). Study 2: Small intestinal permeability was greater in nonpostinfectious diarrhea-predominant IBS (0.84 [0.69–1.49]) compared with postinfectious IBS (0.43 [0.29–0.63], p = 0.028) or controls (0.27 [0.2–0.39]), p = 0.001).CONCLUSIONS:Small intestinal permeability is frequently abnormal in diarrhea-predominant IBS. Those without a history of infectious onset appear to have a more severe defect.

Identifying and testing candidate genetic polymorphisms in the irritable bowel syndrome (IBS): association with TNFSF15 and TNFα

Objectives The postinfectious irritable bowel syndrome (PI-IBS) suggests that impaired resolution of inflammation could cause IBS symptoms. The authors hypothesised that polymorphisms in genes whose expression were altered by gastroenteritis might be linked to IBS with diarrhoea (IBS-D) which closely resembles PI-IBS. Design Part 1: 25 healthy volunteers (HVs), 21 patients 6 months after Campylobacter jejuni infection, 37 IBS-D and 19 IBS with constipation (IBS-C) underwent rectal biopsy for gene expression analysis and peripheral blood mononuclear cell cytokine production assessment. Part 2: Polymorphisms in genes whose expression was altered in Part 1 were assessed in 179 HV, 179 IBS-D, 122 IBS-C and 41 PI-IBS. Results Part 1: Mucosal expression of seven genes was altered in IBS: CCL11, CCL13, Calpain 8 and TNFSF15 increased while NR1D1, GPR161 and GABRE decreased with similar patterns after infection with C jejuni. Part 2: The authors assessed 21 known single nucleotide polymorphisms (SNPs) in these seven genes and one SNP in each of the TNFα and IL-10 genes. Three out of five TNFSF15 SNPs (rs6478108, rs6478109 and rs7848647) showed reduced minor allele frequency (MAF) (0.28, 0.27 and 0.27) in subjects with IBS-D compared with HV (0.38, 0.36 and 0.37; p=0.007, 0.015 and 0.007, respectively) confirming others recent findings. The authors also replicated the previously reported association of the TNFα SNP rs1800629 with PI-IBS which showed an increase in the MAF at 0.30 versus 0.19 for HV (p=0.04). Conclusion IBS-D and PI-IBS patients are associated with TNFSF15 and TNFα genetic polymorphisms which also predispose to Crohns disease suggesting possible common underlying pathogenesis.

Post-infectious irritable bowel syndrome.

Purpose of review Irritable bowel syndrome patients form a heterogeneous group with a variable contribution of central and peripheral components. The peripheral component is prominent in irritable bowel syndrome developing after infection (post-infectious irritable bowel syndrome) and this has proved a profitable area of research. Recent findings Recent studies have overthrown the dogma that irritable bowel syndrome is characterized by no abnormality of structure by demonstrating low-grade lymphocytic infiltration in the gut mucosa, increased permeability and increases in other inflammatory components including enterochromaffin and mast cells. Furthermore, increased inflammatory cytokines in both mucosa and blood have been demonstrated in irritable bowel syndrome. While steroid treatment has proved ineffective, preliminary studies with probiotics exerting an anti-inflammatory effect have shown benefit. Summary The study of post-infectious irritable bowel syndrome has revealed the importance of low-grade inflammation in causing irritable bowel syndrome symptoms. It has suggested novel approaches to irritable bowel syndrome including studies of serotonin and histamine metabolism which may be relevant to other subtypes of of the disease.

The Patient Health Questionnaire 12 Somatic Symptom scale as a predictor of symptom severity and consulting behaviour in patients with irritable bowel syndrome and symptomatic diverticular disease

Background  Anxiety, depression and nongastrointestinal symptoms are often prominent in irritable bowel syndrome (IBS), but their relative value in patient management has not been quantitatively assessed. We modified the Patient Health Questionnaire 15 (PHQ‐15) by excluding three gastrointestinal items to create the PHQ‐12 Somatic Symptom (PHQ‐12 SS) scale.

Non-invasive quantification of small bowel water content by MRI: a validation study

Substantial water fluxes across the small intestine occur during digestion of food, but so far measuring these has required invasive intubation techniques. This paper describes a non-invasive magnetic resonance imaging (MRI) technique for measuring small bowel water content which has been validated using naso-duodenal infusion. Eighteen healthy volunteers were intubated, with the tube position being verified by MRI. After a baseline MRI scan, each volunteer had eight 40 ml boluses of a non-absorbable mannitol and saline solution infused into their proximal small bowel with an MRI scan being acquired after each bolus. The MRI sequence used was an adapted magnetic resonance cholangiopancreatography sequence. The image data were thresholded to allow for intra- and inter-subject signal variations. The MRI measured volumes were then compared to the known infused volumes. This MRI technique gave excellent images of the small bowel, which closely resemble those obtained using conventional radiology with barium contrast. The mean difference between the measured MRI volumes and infused volumes was 2% with a standard deviation of 10%. The maximum 95% limits of agreement between observers were -15% to +17% while measurements by the same operator on separate occasions differed by only 4%. This new technique can now be applied to study alterations in small bowel fluid absorption and secretion due to gastrointestinal disease or drug intervention.

Characterization of the time course of the superior mesenteric, abdominal aorta, internal carotid and vertebral arteries blood flow response to the oral glucose challenge test using magnetic resonance imaging

Blood flow to the splanchnic circulation increases postprandially which may cause a reduction in systemic and cerebral perfusion leading to postprandial syncope in the elderly who lack adequate cardiovascular reserve. We used multi-station 2D phase contrast cine magnetic resonance imaging (PC-MRI) with the aim of characterizing the time course of the haemodynamic response to an oral glucose challenge test (OGCT) in the large arteries perfusing the splanchnic, systemic and cerebral circulations (superior mesenteric artery SMA, abdominal aorta AA, internal carotid arteries, ICA and vertebral arteries VA). In this study nine fasted healthy volunteers were studied. Separate cine PC-MRI scans were acquired in the neck and in the abdomen every 88 s, these two measurements being interleaved for ten baseline scans at each station with the scanner automatically moving the subject between the two stations. After ingestion of the OGCT, a further 30 cine PC-MRI scans were acquired at each station. Using this technique we were able to characterize with frequent sampling of volumetric blood flow the time course of blood flow response to the OGCT of the SMA, AA and both VA and ICA. We found a substantial variation between individuals in the amplitude and the time to the peak of the SMA blood flow response to the OGCT which correlated positively with body mass index. MRI provides a robust, non-invasive method of studying normal physiology that could be valuable in studies of diseases such as postprandial hypotension.