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Immune-mediated Effects of Lactitol in Animals with Antibiotic-induced Dysbiosis after Infection with Clostridium Difficile

Abstract

A. A. Sergeev1*, N. A. Mnafki, E. A. Ryabenko, A. A. Nikitina, C. Shammas, E. Nikolaou, A.V. Dikovskiy, T.I.Kombarova, O. V. Korobova, E. A. Ganina, I. P. Mitsevits, A. I. Borzilov3, M. V. Khramov and L. C. Zacharia

The research objective was to study the effect of dysbiosis in mice and hamsters caused by the treatment with combination of amoxicillin trihydrate and potassium clavulanate on the colonization with Clostridium difficile (C. difficile) and course of C. difficile infection (CDI), to estimate the effect of the prebiotic lactitol when was administered with antibiotic for prevention and therapy of the CDI. CDI is a current public health problem. The combination of amoxicillin and clavulanic acid is considered an antibiotic with high risk of adverse CDI. Meanwhile, prebiotics as a substrate for bacteria, are able to normalize the composition of the microbiota damaged by antibiotics and could prevent CDI. It was found that lactitol in animals led to a significant 10-fold decrease in excretion of C. difficile from mice feces, and 2.5-fold decrease in feces of infected hamsters, compared with animals who weren’t administered prebiotic. Besides, in mice with CDI, when lactitol was administered, a 53% decrease in the response of lymphocytes and 1.5-fold increase in level of immunoglobulin G was observed 10 days after infection in comparison with animals without lactitol administration. In hamsters, lactitol normalized ratio between granulocytes and lymphocytes at first day after infection. Analysis of the mice intestinal microbiota by 16s rRNA sequencing showed positive trends in a shift of the microbiota profile for the bacterial families Lactobacilliaceae, Erysipelotrichaceae. Thus, we demonstrated that of co-administration lactitol with Amoxicillin and Clavulanate reduce development of CDI, and maintain the immune system of animals to increase effectiveness of host response.

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