Rectal Administration of Lactobacillus casei DG Modifies Flora Composition and Toll-Like Receptor Expression in Colonic Mucosa of Patients with Mild Ulcerative Colitis

Abstract

An imbalance in gut microbiota seems to contribute to the development of chronic inflammatory disorders of the gastrointestinal tract, such as ulcerative colitis (UC). Although it has been suggested that probiotic supplementation is an effective approach to colitis, its effects on intestinal flora and on mucosal cytokine balance have never been explored. To evaluate the effect of Lactobacillus casei (L.casei) DG, a probiotic strain, on colonic-associated microbiota, mucosal cytokine balance, and toll-like receptor (TLR) expression. Twenty-six patients with mild left-sided UC were randomly allocated to one of three groups for an 8-week treatment period: the first group of 7 patients received oral 5-aminosalicylic acid (5-ASA) alone, the second group of 8 patients received oral 5-ASA plus oral L.casei DG, and the third group of 11 patients received oral 5-ASA and rectal L.casei DG. Biopsies were collected from the sigmoid region to culture mucosal-associated microbes and to assess cytokine and TLR messenger RNA (mRNA) levels by quantitative real-time polymerase chain reaction (RT-PCR). 5-ASA alone or together with oral L.casei DG failed to affect colonic flora and TLR expression in a significant manner, but when coupled with rectally administered L.casei DG, it modified colonic microbiota by increasing Lactobacillus spp. and reducing Enterobacteriaceae. It also significantly reduced TLR-4 and interleukin (IL)-1β mRNA levels and significantly increased mucosal IL-10. Manipulation of mucosal microbiota by L.casei DG and its effects on the mucosal immune system seem to be required to mediate the beneficial activities of probiotics in UC patients.