Antibiotics versus probiotic treatments in the mdr1a −/− mouse model of colitis

Ulcerative colitis (UC) is achronic inflammatory disease of the gut whose etiology is multifactorial. Mdr1a knock out mice raised in conventional housing develop a chronic colitis similar to UC. We hypothesized that modulation of the microbiota with antibiotics, probiotics or a synbiotic treatment may alter the outcome of disease in this mouse model. Four‐ and 12‐week‐old mice, i.e., before and after onset of clinical colitis, were treated for 2 and 4 weeks with streptomycin‐neomycin‐amphotericin‐bacitracin (SNAB), with neomycin‐metronidazole (NM), with S. thermophilus‐L. acidophilus (ST/LA) or with ST/LA plus inulin (ST/LA/IN). At the end of treatment, colon tissue was tested for transepithelial resistance (TER) as well as baseline and stimulated ion transport (measured as short circuit current (I sc )) in Ussing chambers. Colitis was assessed histologically, and colonic segments were also tested for bacterial numbers, myeloperoxidase (MPO) activity, and cyclooxygenase‐2 (COX‐2) and inducible nitric oxide synthase (iNOS) levels. Probiotic or synbiotic treatment of 4 wk‐old mice significantly reduced subsequent diarrhea (100%, respectively; p<0.001) and weight loss (28.5 ±1.0, 30.5±1.5 vs . 21.5±0.5 g, respectively; p<0.01) vs . placebo, whereas antibiotics had limited effect. Similarly, probiotic or synbiotic treatment significantly ameliorated electrophysiological parameters and markers of inflammation in both age groups of mutant mice. Our results suggest the importance of restoring normal levels of lactic acid bacilli in the microbiota for the prevention and treatment of chronic colitis. Supported by grants NIH‐AT01180, CCFA Senior Research Award (KEB), and NIH‐ DK062096 (SRL)