Epidemiological studies revealed that antibiotics exposure increases a risk of inflammatory bowel diseases (IBD) development. It remained largely unknown how antibiotic-induced dysbiosis confers the risk for enhanced inflammatory response. The aim of the present study was to test the hypothesis that SCFAs, their receptors and transporters mediate the antibiotic long-term effects on the functional state of colonic mucosa and susceptibility to the experimental colitis. Male Wistar rats were treated daily for 14 days with antibiotic ceftriaxone (300 mg/kg, i.m.) or vehicle; euthanized by CO 2 inhalation followed by cervical dislocation in 1, 14 or 56 days after antibiotic withdrawal. We found increased cecum weight and sustained changes in microbiota composition after ceftriaxone treatment with increased number of conditionally pathogenic enterobacteria, E . coli , Clostridium , Staphylococcus spp . and hemolytic bacteria even at 56 days after antibiotic withdrawal. The concentration of SCFAs was decreased after ceftriaxone withdrawal. We found decreased immunoreactivity of the FFA2, FFA3 receptors, SMCT1 and increased MCT1 & MCT4 transporters of SCFAs in colon mucosa. These changes evoked a significant shift in colonic mucosal homeostasis: the disturbance of oxidant-antioxidant balance; activation of redox-sensitive transcription factor HIF1α and ERK1/2 MAP kinase; increased colonic epithelial permeability and bacterial translocation to blood; morphological remodeling of the colonic tissue. Ceftriaxone pretreatment significantly reinforced inflammation during experimental colitis 56 days after ceftriaxone withdrawal, which was confirmed by increased histopathology of colitis, Goblet cell dysfunction, colonic dilatation and wall thickening, and increased serum levels of inflammatory cytokines (TNF-α and IL-10). Since the recognition of the importance of microbiota metabolic activity rather than their composition in the development of inflammatory disorders, e.g. IBD, the present study is the first report on the role of the SCFA system in the long lasting side effects of antibiotic treatment and its implication in IBD development.

Short-chain fatty acids (SCFAs) T he interchange of low molecular weight metabolites between gut microorganisms and macroorganism have attracted a lot of attention during last years [1][2][3]. The gut microbiota affects predominantly host physiology by the production of short-chain fatty acids (SCFAs). SCFAs are saturated aliphatic organic acids that consist of one to six carbons of which acetate (C2), propionate (C3), and butyrate (C4) are most abundant (≥95%). Acetate, propionate, and butyrate are present in an approximate molar ratio of 60:20:20 in the colon and stool [4]. Depending on the diet, the total maximum concentration of SCFAs decreases from 70 to 140 mM in the proximal colon from 20 to 70 mM in the distal colon [5].These metabolites, especially butyrate, serve as an important source of energy for the intestinal epithelial cells, providing about 60-70% of their ener gy demand. Colonocytes from germ-free mice are in an energy-deprived state and exhibit decreased expression of enzymes that catalyze key steps in intermediary metabolism including the tricarboxylic acid cycle. Consequently, there is a marked decrease in NADH/NAD + , oxidative phosphorylation, and ATP levels, that results in AMP-activated protein kinase activation, cyclin-dependent kinase inhibitor 1B phosphorylation and autophagy. When butyrate is added to germ-free colonocytes, it rescues their deficit in mitochondrial respiration and prevents them from undergoing autophagy [6].

Osteoarthritis is a most widespread chronic degenerative joint disease that causes pain, cartilage deformation, and joint inflammation. Adverse alterations of intestinal microbiota like dysbiosis may lead to metabolic syndrome and inflammation, two important components of osteoarthritis progression. Aim. In this study we investigated the effect of chondroitin sulfate and probiotics on the gut microbiome in monoiodoacetate-induced osteoarthritis model in rats. Methods. The species and quantitative composition of feces were determined using diagnostic media with selective properties. Further identification of isolated microorganisms was carried out according to morphological, tinctorial, physiological and metabolic parameters. The results are presented in the form of lg CFU/g. Results. Induction of osteoarthritis caused significant increasing the number of opportunistic enterobacteria and lactose-negative Escherichia coli against the decreasing of lacto- and bifidobacteria that may indicate a dysbiotic condition. Coadministration of chondroitin sulfate and probiotic bacteria has led to improvement the quantitative composition of the gut microbiota in experimental animals, the numerous of Bifidobacterium, Lactobacillus were increasing against decreasing the quantitative composition of opportunistic microorganisms. Conclusions. Monoiodoacetate-induced osteoarthritis caused dysbiosis of gut in rat. We observed beneficial effect of combined administration of chondroitin sulfate and probiotics on gut microbiota composition in rats with experimental osteoarthritis. Thus, adding of supplements like probiotics to standard treatment of osteoarthritis may have potentials to prevent and treat this disease.

Changes in the composition of intestinal microbiota, namely the reduction of microorganisms capable of metabolizing oxalates, is one of the main factors in the development of hyperoxaluria. The purpose of this study was to determine the quantity of oxalate-degrading bacteria in fecal biopsy of different species of laboratory animals and to investigate the relationship between the amount of oxalate in the diet and the level of oxalate-degrading bacteria. The object of the study was the content of oxalate-degrading bacteria in fecal biopsy of experimental animals: nonbreeding rats (n = 12); Wistar rats (n = 12); mice Balb C line (n =12); сhinchilla rabbits (n= 10). The quantity of oxalate-degrading bacteria was determined by culture method on a highly selective Oxalate Medium. Current data shows that the content of oxalate-degrading bacteria in fecal biopsy depends on the species of the animals and the high content of oxalates in the diet. In Wistar line rats, oxalate-degrading bacteria were found in 100 % of the animals, in non-breeding rats – 58 %, in mice Balb C line – 42 %, in сhinchilla rabbits – 7 %. The highest quantity of oxalatedegrading bacteria in grams of fecal biopsy was found in Wistar rats – lg 6,12 ± 0,63 CFU/g, in non-breeding rats – lg 2,97 ± 0,34 CFU/g, in mice lg 2,4 ± 0,41 CFU/g. The least quantity of oxalate-degrading bacteria was detected in rabbits (lg 2,1 ± 0,5 CFU/g). A 14-day administration of Na2C2O4 to non-breeding rats has led to an increase in the quantity of oxalate-degrading bacteria in fecal biopsy. During the first seven days of the high-oxalate diet 57 % animals had increased the quantity of oxalate-degrading bacteria in a gram of feces. After 14 days, the further increase of oxalatedegrading bacteria in a gram of feces was observed in 25 % animals. In general, the quantity of oxalate-degrading bacteria during high-oxalate diet has increased by two orders. Animals with non-detectable level of oxalate-degrading bacteria in feces might be attributed to the potential risk group of hyperoxaluria and the formation of oxalate stones.

n the aspect of the existence of the gut brain axis are considered quantitative changes of the distal part of colon's microbiota (Mb) under conditions of experimental parkinsonism. Studies were done on laboratory non-linear male rats (140–160 g, n = 7). Parkinsonism was modeled by onesided destruction of the dopaminergic neurons of a compact part of the substantia nigra of brain, causing by stereotaxic microinjections 12 mg neurotoxin 6-OHDA (Sigma-Aldrich, Germany) in the left lateral ascending bundle. Changes in the quantitative Mb composition were determined bacteriologically by sowing 10-fold dilutions of fecal biopsy on differential diagnostic media (HiMedia, India) in 1, 1.5, 2 months after induced parkinsonism. Research has been shown that within the fecal Mb of rats, within 2 months from the beginning of the experiment, significant changes were detected only for E.coli. The amount of lac(+) E.coli increased from 1,5 months to 2 folds (from lg 4,65 ± 0,80 CFU/g to lg 6,08 ± 0,70 CFU/g (1,5 months), after 2 months – from lg 4.39±0.55 CFU/g to lg 6.24±1.26 CFU/g. At the same time, the amount of E.coli lac(-) decreased by 2-3 folds. The number of the genus Bifidobacterium and Lactobacillus remained within the control values. After 2 months after induced parkinsonism, there was a tendency to increase the number of Clostridium species. These results suggest minor microbiota changes of 6-OHDA-induced parkinsonism in rats. These results are preliminary and require more detailed study.