Investigation of the change in blood glucose levels due to antibiotic induced microbiota damage in rats and the potential of probiotics to prevent this change

The gut microbiota, which plays a significant role in the host's physiology and the pathophysiology of certain diseases, has increasingly become a prominent area of study. One of the important relationships discovered in recent years is the connection between the gut microbiota and the host's glucose metabolism. Studies conducted on germ-free mice have shown that these mice tend to exhibit lower blood glucose levels compared to normal mice. Furthermore, similar results have been observed in animals whose microbiota was disrupted using combined antibiotics. The reduction in blood glucose levels has been reversible upon the recolonization of gut bacteria. This thesis investigates the effects of administering neomycin, metronidazole, and levofloxacin antibiotics via drinking water in rats, examining changes in blood glucose levels, body weights, and alterations in gut microbiota. Furthermore, it was planned to examine the potential of preventing antibiotic-induced changes by giving Lactobacillus plantarum type probiotics to some groups daily via oral gavage. Wistar albino rats were given antibiotics and probiotics for a duration of 10 days, during which fasting blood glucose levels were measured four times (on days 1, 4, 7, and 11), and body weights were recorded at the beginning and end of the experiment. Additionally, microbiota compositions were assessed through 16S rRNA sequencing of fecal samples collected at the end of the experiment. At the end of the study, no significant effect on blood glucose levels was seen with neomycin, while significant decreases in blood glucose levels were noticed with metronidazole and levofloxacin. In all groups given antibiotics, blood glucose levels were decreased while the reductions in metronidazole and neomycin groups were statistically significant. Analysis of microbiota data revealed a decrease in species diversity in all antibiotic-administered groups, with the least change observed in the neomycin group and the most significant changes in the levofloxacin group. In the metronidazole probiotic, levofloxacin and levofloxacin probiotic groups, where the most significant decreases in blood glucose levels were observed, phylogenetic diversity was found to decrease statistically significantly according to alpha diversity analysis. Our study indicated that neomycin increased the ratio of Bacteroidota and Cyanobacteria species in the gut microbiota while decreasing Firmicutes and Proteobacteria species; metronidazole increased the ratio of Bacteroidota and Proteobacteria species while decreasing Firmicutes; levofloxacin increased the ratio of Bacteroidota species while decreasing Firmicutes and completely eliminated Proteobacteria, Verrucomicrobiota, Cyanobacteria and Patescibacteria species. Although the Lactobacillus plantarum type probiotic affected the microbiota changes caused by antibiotics, it was shown that it could not sufficiently prevent the decrease in blood glucose levels. In addition, it was observed that body weights decreased in the group given only probiotics compared to the control group, and this effect was also prominent in the groups given probiotics together with metronidazole and levofloxacin. Our study is the first to investigate the combined effects of blood glucose levels and microbiota alterations for all three antibiotics used individually. Previous studies on levofloxacin-induced hypoglycemia have focused on potassium channels in the pancreas. Our findings suggest that the decrease in blood glucose levels associated with metronidazole and levofloxacin may be related to their effects on the gut microbiota. To examine this relationship in more detail, new studies with detailed parameters and evaluating data over a longer period after antibiotic administration may contribute to the literature.