Antibiotic induced Klebsiella spp. overgrowth treatment by probiotics Ermolenko E. 1,2, Klimina K.3, E. Tarasova1, 4, A. Eliseev 4, M. Kotyleva 1,2 Borschev Y.1, A., Danilenko V.3, Suvorov 1,2 1Institute of experimental medicine, 2 St. Petersburg State University, St. Petersburg, 3Vavilov Institute of General Genetics, Moscow, 4SRL Explana, St. Petersburg, Russsia

Introduction It was revealed using all the methods that the Bacteriological study Design of study maximal number of Klebsiella spp. (Routella spp.) was found in groups L, E and C1 (Fig.2.) The After administration of antibiotics during Enterococcus spp. content elevation in the gut was 3 days the following changes in gut The continuing emergence of infections due to Groups 1-3 days 3-8 days observed using MetG only in groups B and M. microbiota of rats were registered: of rats multidrug resistant bacteria is a serious public health decrease (1-2 lg CFU/ml) of bacteria L. L. rhamnosus K32 80,00 problem. Klebsiella pneumoniae, which commonly belonging to the genera Bifidobacterium, E. faecium L3 70,00 acquires resistance to different antibiotics, is a prime E. Lactobacillus, Escherichia coli and B.longum GT15 60,00 example if opportunistic bacteria capable for causing Enterococcus; appearance or increase (2- B. Ampicillin+ L. rhamnosus K32+ 50,00 5.5 lg CFU/ml) in the quantity of serious human infections as result of antibiotic therapy metronidazole E. faecium L3 + 40,00 putative opportunistic bacteria such as M. (Gazin M . et al., 2012, Li B. еt al., 2014). Probiotics B.longum GT15 30,00 Klebsiella spp. The quantity of last one could be applied as the drugs of choice in case of Control 1 Sucrose and gelatin 20,00 was decreased only in groups M, B and Klebsiella spp. overgrowth. However little is known about 10,00 E, in contrast of groups L and C1. The Control 2 Water Sucrose and gelatin 0,00 the specific antimicrobial activity of various probiotics in Lactobacillus Enterococcus Raoultella Bacteroides least amount of Enterococcus spp., was reveled in groups C1. vivo. The aim of this study was to reveal the differences L E B M С1 С2 between the influence of different probiotic strains and Results Figure 2. The diversity of different bacterial genera (%). 7 their mixture on the microbiota of rats in condition of the in the rat gut microbiota after the probiotic correction intestinal dysbiosis associated with overgrowth of Metagenomic analysis of dybiosis ( by MetG). 6 RT-PCR Klebsiella spp. 5 CFU/g

MetG showed that the content, in lg Proteobacteria Klebsiella spp. was not determined by RT- particular members of family was 4 Enterobacteriaceae PCR in microbiota of rats treated with probiotic less prevalent in group C2 than in other groups. The 3 Material and methods bifidobacteria, enterococci and their mixture It maximal values of these parameters were found in was found bacteriologically and by RT-PCR that 2 groups L, E and C1 (Figure 1). In groups L and C1 the the quantity of Lactobacillus spp. increased in Male Wistar rats with high content of Klebsiella spp. in quantity of was less represented than in 1 Firmacutes groups E, B and M than in groups L and C2 feces (>105 CFU/g) after consumption of antibiotics other animals. 0 (Fig.3). In the groupe E. F. prausnitzii was more (ampicillin® and metronidazole® for 3 days) were used in Klebsiella spp. Enterococcus spp. prevalent relatively to the other groups. L B E M C1 C2 this study. The animals were divided into 4 experimental 100 Bacteroides fragilis in this group was detected groups and were getting different probiotic strains determined to a lesser extent. Figure 4. The diversity of different genera (%). intragastrically for 5 days: Lactobacillus rhamnosus K32 80 in the rat gut microbiota after the probiotic correction of dybiosis ( by MetG). (L), Bifidobacterium longum GT15 (B), Enterococcus 60 The gut microbiota study being faecium L3 (E) or their mixture (M). Rats from the first 40 control group (C1) didn`t receive probiotics. The animals performed by several methods provides from the second control group (C2) didn`t receive both 20 more detailed and complementary antibiotics and probiotics. Study of fecal samples, 0 information about its content. Probiotics collected on the 9th day of the experiment, was performed Firmicutes Proteobacteria can significantly decrease the Klebsiella L E B M С1 C2 by real time PCR (RT-PCR), metagenomic analysis MetG) spp. overgrowth in strain dependent manner. The complex of probiotic strains using GS Junior, Roche 454 and bacteriologically. Figure 1. The diversity of different bacterial phylums Figure 3. The quantitative content of different bacteria in can be more efficient than its individual (%). in the rat gut microbiota after the probiotic the rat gut microbiota after the probiotic correction of correction of dybiosis (by MetG). dybiosis (by RT-PCR) components in normalization of intestinal microbiota. Work was supported by grant 13-04-01861 and the Ministry of Education and Science of the Russian Federation (State grant 14.N08.12.0021).