Antal Bajor

Physical Activity Improves Symptoms in Irritable Bowel Syndrome: A Randomized Controlled Trial

OBJECTIVES:Physical activity has been shown to be effective in the treatment of conditions, such as fibromyalgia and depression. Although these conditions are associated with irritable bowel syndrome (IBS), no study has assessed the effect of physical activity on gastrointestinal (GI) symptoms in IBS. The aim was to study the effect of physical activity on symptoms in IBS.METHODS:We randomized 102 patients to a physical activity group and a control group. Patients of the physical activity group were instructed by a physiotherapist to increase their physical activity, and those of the control group were instructed to maintain their lifestyle. The primary end point was to assess the change in the IBS Severity Scoring System (IBS-SSS).RESULTS:A total of 38 (73.7% women, median age 38.5 (19–65) years) patients in the control group and 37 (75.7% women, median age 36 (18–65) years) patients in the physical activity group completed the study. There was a significant difference in the improvement in the IBS-SSS score between the physical activity group and the control group (−51 (−130 and 49) vs. −5 (−101 and 118), P=0.003). The proportion of patients with increased IBS symptom severity during the study was significantly larger in the control group than in the physical activity group.CONCLUSIONS:Increased physical activity improves GI symptoms in IBS. Physically active patients with IBS will face less symptom deterioration compared with physically inactive patients. Physical activity should be used as a primary treatment modality in IBS.

Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain

Aliment Pharmacol Ther 2011; 33: 1113–1122

Randomised clinical trial: the ileal bile acid transporter inhibitor A3309 vs. placebo in patients with chronic idiopathic constipation – a double‐blind study

Aliment Pharmacol Ther 2011; 34: 41–50

Increased colonic bile acid exposure: a relevant factor for symptoms and treatment in IBS

Objective Bile acids may play a role in the pathogenesis of IBS. We investigated the potential effects of bile acids entering the colon and its role in the symptom pattern in IBS. Design We measured 75Se-labelled homocholic acid-taurine (75SeHCAT) retention, and serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor (FGF) 19 in patients with IBS (n=141) and control subjects (75SeHCAT n=29; C4 and FGF19 n=435). In patients with IBS stool frequency and form, as well as GI symptom severity were registered, and in a proportion of patients colonic transit time and rectal sensitivity were measured (n=66). An 8-week open-label treatment with colestipol was offered to patients with 75SeHCAT <20%, and the effect of treatment was evaluated with IBS severity scoring system and adequate relief of IBS symptoms. Results Compared with controls, patients with IBS had lower 75SeHCAT values (p=0.005), higher C4c levels (C4 corrected for cholesterol) (p<0.001), but similar FGF19 levels. Abnormal 75SeHCAT retention (<10%) was seen in 18% of patients, whereas 23% had elevated C4c levels. Patients with IBS with 75SeHCAT retention <10% had more frequent stools, accelerated colonic transit time, rectal hyposensitivity, a higher body mass index, higher C4c and lower FGF19 levels. Colestipol treatment improved IBS symptoms (IBS severity scoring system 220±109 vs 277±106; p<0.01), and 15/27 patients fulfilled criteria for treatment response (adequate relief ≥50% of weeks 5–8). Conclusions Increased colonic bile acid exposure influences bowel habit and colonic transit time in patients with IBS. A high response rate to open label treatment with colestipol supports this, but placebo-controlled studies are warranted.

Review article: bile acid diarrhoea - pathogenesis, diagnosis and management.

Bile acid diarrhoea results from imbalances in the homoeostasis of bile acids in the enterohepatic circulation. It can be a consequence of ileal disease/dysfunction, associated with other GI pathology or can be idiopathic.

Anti-TNF Therapy Response in Patients with Ulcerative Colitis Is Associated with Colonic Antimicrobial Peptide Expression and Microbiota Composition

BACKGROUND AND AIMS Anti-tumour necrosis factor [TNF] therapy is used in patients with ulcerative colitis [UC], but not all patients respond to treatment. Antimicrobial peptides [AMPs] and the gut microbiota are essential for gut homeostasis and may be important for treatment outcome. The aim of this study was to determine AMP and microbiota profiles in patients with UC before anti-TNF therapy start and correlate these data to treatment outcome. METHODS Serum and biopsies were obtained from UC patients naïve to biological therapy [n = 56] before anti-TNF therapy start [baseline]. Fecal samples were taken at baseline and Weeks 2 and 6. Quantitative proteomic analysis was performed in mucosal biopsies. Expression of AMPs and cytokines was determined in biopsies and serum. Microbiota analysis of fecal samples was performed using GA-map™ Dysbiosis Test and real-time quantitative polymerase chain reaction [rtPCR]. Treatment response was evaluated 12-14 weeks after baseline. RESULTS At baseline, proteomic analysis of biopsies showed that treatment responders and non-responders had differential expression of AMPs. Eleven AMP and AMP-related genes were analysed by rtPCR in mucosal biopsies and could together discriminate responders from non-responders at baseline. The most important nominators for response were increased expression of defensin 5 and eosinophilic cationic protein. Microbiota analysis revealed lower dysbiosis indexes and higher abundance of Faecalibacterium prausnitzii in responders compared with non-responders at baseline. Also, abundance of F. prausnitzii increased during induction therapy in responders. CONCLUSIONS Anti-TNF therapy responders and non-responders display distinctly separate patterns of mucosal AMP expression and gut microbiota before treatment start. This indicates that intestinal antimicrobial/microbial composition can influence treatment outcome.

Response to infliximab therapy in ulcerative colitis is associated with decreased monocyte activation, reduced CCL2 expression and downregulation of Tenascin C.

BACKGROUND AND AIMS The cellular mechanisms leading to infliximab therapy response in patients with ulcerative colitis (UC) are incompletely known. We therefore investigated early effects of infliximab therapy on monocytes and associated chemokines linked to clinical therapy response in UC patients. METHODS Blood and biopsies were obtained from anti-TNF therapy-naïve UC patients (n = 43) before (baseline) and during induction therapy with infliximab. Therapy response was evaluated at Week 14. Expression of monocyte activation markers and levels of chemokines in serum and biopsies were determined. Quantitative proteomic analysis was performed in cultured mucosal biopsies, and obtained data was validated in serum. RESULTS In therapy responders, but not in non-responders, infliximab reduced blood monocyte expression of CD14 and CD86, 2 weeks after therapy commenced, relative to baseline. Serum CCL2 levels were decreased only among therapy responders at Week 2 and Week 14, relative to baseline. These data corresponded with lower levels of CD14, CD86 and CCL2 in intestinal tissue in responders as compared with non-responders at Week 14. Proteomic analysis of cultured biopsies showed that infliximab induced a reduction in Tenascin C that predicted downregulation of CCL2. Therapy responders, but not non-responders, had decreased serum Tenascin C levels at Week 2 and Week 14, relative to baseline. CONCLUSIONS Infliximab therapy response in UC patients is associated with reduced monocyte activation and serum levels of CCL2 2 weeks after therapy commencement. In therapy responders, infliximab influenced Tenascin C, which might be a regulator of CCL2 expression and important for induction of the clinical therapy response.

Global mucosal and serum cytokine profile in patients with ulcerative colitis undergoing anti-TNF therapy.

Abstract Background and objective. The knowledge of the effects of anti-tumour necrosis factor (TNF) treatment on the global cytokine profile in patients with ulcerative colitis (UC) is limited. A better understanding of these mechanisms could improve the ability to select patients that should undergo the therapy. Therefore, the aim was to determine the global mucosal and serum cytokine profile before and during induction therapy with anti-TNF in UC patients. Materials and methods. In total, mucosal biopsies (n = 28) and serum samples (n = 42) were collected from UC patients (total n = 48) before anti-TNF therapy. At week 14 response to the therapy was evaluated and again mucosal biopsies (n = 14) and serum samples (n = 42) were collected. Quantitative real-time PCR was used to determine mucosal cytokine mRNA expression and the MSD MULTI-ARRAY assay system platform was used for analysis of cytokines in serum. The global cytokine profile was evaluated by multivariate factor analysis. Results. At baseline, the global profile of mucosal cytokine mRNA expression and serum cytokines discriminated therapy responders from non-responders. Responders had lower mucosal mRNA expression of interleukin 1β (IL-1β), IL-17A, IL-6 and interferon γ (IFN-γ) than non-responders. Fourteen weeks after therapy start mucosal IL-1β and IL-6 were down-regulated in therapy responders but not in non-responders. At week 14, serum levels of IL-6 were decreased in therapy responders whereas IFN-γ and IL-12p70 were increased in non-responders. Conclusions. Our data suggest that patients with a therapy failure have a more severe pro-inflammatory cytokine profile before start of anti-TNF treatment, which is less well suppressed by the treatment as compared to therapy responders.

Indirect evidence for increased mechanosensitivity of jejunal secretomotor neurones in patients with idiopathic bile acid malabsorption

Aim:  The interdigestive motor rhythm, the migrating motor complex (MMC), is accompanied by active secretion of chloride during periods of distally propagating maximal motor activity (MMC phase III). We studied the behaviour of this system in bile acid malabsorption (BAM), a relative common cause of chronic diarrhoea. We measured motor activity and transmucosal potential difference (PD, reflecting active chloride secretion), in the proximal jejunum in healthy controls (n = 18) and in a group of patients with BAM (n = 11). The phase III‐generated voltage was related to the degree of BAM quantified by the 75SeHCAT test.

CD25 and TNF receptor II reflect early primary response to infliximab therapy in patients with ulcerative colitis

Background Although infliximab treatment is an option for patients with ulcerative colitis (UC), not all patients do respond to therapy, and cellular mechanisms leading to therapy response are incompletely known. Objective The objective of this article is to determine early effects of infliximab therapy on T cells in the blood of UC patients and if effects differed in therapy responders and nonresponders. Methods: Blood samples were obtained before and two weeks post-treatment start from 34 anti-tumor necrosis factor (TNF) therapy-naïve UC patients undergoing infliximab therapy. Response to therapy was evaluated prior to the fourth treatment dose. Expression of T cell surface markers and levels of soluble receptors and cytokines in serum were determined. Results At baseline, there were no differences in cellular, biochemical or clinical parameters between therapy responders and nonresponders. Infliximab therapy reduced frequencies of CD25+ T cells and increased frequencies of annexin V+ T cells in patients responding to infliximab, but not in nonresponding patients, two weeks after therapy start. Only therapy responders had decreased serum levels of sCD25 and sTNFRII two weeks after treatment start. In contrast, clinical parameters did not reflect therapy outcome already two weeks after therapy start. Conclusion Soluble and membrane-bound T cell receptors may be early indicators of infliximab therapy response in UC, which can be of clinical importance for the decision when to continue or to stop the treatment.