Cytokine and clinical response to Saccharomyces boulardii therapy in diarrhea-dominant irritable bowel syndrome: a randomized trial Zaigham Abbas a , Javed Yakoob a , Wasim Jafri a , Zubair Ahmad b , Zahid Azam a , Muhammad W. Usman b , Sara Shamim a and Muhammad Islam c Introduction This preliminary study aimed to investigate the effects of the probiotic Saccharomyces boulardii on proinflammatory and anti-inflammatory cytokines in patients with diarrhea-dominant irritable bowel syndrome (IBS-D). The other objectives were to document any clinical improvement as judged by symptoms, quality of life, and histology. Patients and methods This was a randomized, double blind, placebo-controlled trial in which S. boulardii, 750 mg/ day, or placebo was administered for 6 weeks in IBS-D patients, in addition to ispaghula husk standard treatment. Results Thirty-seven patients received S. boulardii and 35 patients received the placebo. As compared with placebo, the S. boulardii group showed a significant decrease in blood and tissue levels of proinflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor-a (P < 0.001) and an increase in anti-inflammatory IL-10 levels, as well as an increase in the tissue IL-10/IL-12 ratio (P < 0.001). No significant change in the blood and tissue levels of cytokines was found in the placebo group. Bowel-related IBS-D symptoms reported in the patients’ daily diary improved in both groups. However, overall improvement in the quality of life was more marked in the S. boulardii group. Although baseline histological findings were mild, an improvement was observed in the probiotic group in the lymphocyte and neutrophil infiltrates (P = 0.017 and 0.018), epithelial mitosis (P = 0.003), and intraepithelial lymphocytes (P = 0.024). No serious adverse events were found in either group. Conclusion S. boulardii with ispaghula husk was superior to placebo with ispaghula husk in improving the cytokine profile, histology, and quality of life of patients with IBS-D. These preliminary results need to be confirmed in a well-powered trial. Eur J Gastroenterol Hepatol 26:630–639  c 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. European Journal of Gastroenterology & Hepatology 2014, 26:630–639 Keywords: cytokine, irritable bowel syndrome, probiotic, Saccharomyces boulardii Departments of a Medicine, b Pathology and c Community Health Sciences, The Aga Khan University Hospital, Karachi, Pakistan Correspondence to Zaigham Abbas, MD, FCPSP, FACP, FACG, FRCP, Department of Medicine, The Aga Khan University, Karachi 74800, Pakistan Tel: + 92 321 200 0482; fax: + 92 213 493 4294; e-mail: zaigham.abbas@aku.edu Received 1 January 2014 Accepted 5 March 2014 Introduction Irritable bowel syndrome (IBS) is a chronic condition characterized by intermittent abdominal pain, altered bowel habits (diarrhea and/or constipation), and other gastrointestinal symptoms, such as bloating and flatulence, all occurring in the absence of structural abnormalities in the intestine [1]. The prevalence of IBS in the general population ranges between 3 and 25%, and a significant impact on patients’ quality of life (QOL) has been described [2,3]. The pathophysiology of IBS is not well understood, but the syndrome is associated with a dysregulation of the brain–gut axis, which involves abnormal function in the enteric, autonomic, and/or central nervous systems, or disturbed interplay between the two systems [4]. These alterations are considered to lead to abnormal gastrointestinal sensitivity, motility, and secretion, which in turn contribute toward the hallmark IBS symptoms. Some studies have evidenced an important role of low- grade inflammation and immunological alterations in the development of symptoms compatible with IBS [4,5]. Mild infiltration of immune cells (mainly T cells and mast cells) and increased levels of plasma/serum proinflamma- tory cytokines, including interleukin-1b (IL-1b), tumor necrosis factor-a (TNF-a), IL-6, and IL-8, have been observed in IBS patients compared with controls [5]. One of the events considered to induce the immunological response impacting the generation of IBS symptoms is alterations in the gut microflora (bacterial overgrowth) [4]. Significant differences have been described in the gut microbiota of IBS patients compared with healthy individuals [6,7] and infectious gastroenteritis has been associated with increased chances of developing IBS symptoms [8,9]. It remains unclear whether changes in the intestinal microbiota are a cause or a consequence of IBS [10]. Probiotics are defined as ‘live microorganisms which when administered in adequate amount confer a health benefit on the host’ [11]. Saccharomyces boulardii is a probiotic yeast that has been used successfully to prevent 630 Original article 0954-691X  c 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/MEG.0000000000000094 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.