ABSTRACT
A simple model of alternative microbiota in the developing intestinal environment has been highly desirable for the study of health and disease in the gut. The pattern of antibiotic depletion of natural gut microbes is necessary for this model. However, the effects and loci of antibiotic deletion of gut microbes remain unclear. In this study, a mixture of three proven broad-spectrum antibiotics was selected to study their effects on microbial deletions in the jejunum, ileum, and colon of mice. The 16S rRNA sequencing results showed that antibiotics significantly reduced colonic microbial diversity, with limited effects on the jejunum and ileum. At the level of microbial genera, only 93.38% of Burkholderia-Caballeronia-Paraburkholderia and 5.89% of Enterorhabdus were present in the colon after antibiotic treatment. However, such changes were not observed in the microbial composition of the jejunum and ileum. Our results suggest that the antibiotics depleted intestinal microorganisms by acting primarily in the colon and not in the small intestine (jejunum and ileum). IMPORTANCE Many studies have applied antibiotics to delete intestinal microbes to shape pseudosterile mouse models and further used for fecal microbial transplantation. However, few studies have explored the spatial location of antibiotic action in the intestine. This study shows that the selected antibiotics effectively deleted microbiota in the colon of mice, with limited effects on microbes in the jejunum and ileum. Our study provides guidance for the application of a mouse model of antibiotic deletion of intestinal microbes.
Subject(s)
Anti-Bacterial Agents , Gastrointestinal Microbiome , Animals , Mice , Anti-Bacterial Agents/pharmacology , RNA, Ribosomal, 16S/genetics , Intestine, Small , ColonABSTRACT
Reputed as a significant metabolic disorder, non-alcoholic fatty liver disease (NAFLD) is characterized by high-fat deposits in the liver and causes substantial economic challenges to any country's workforce. Previous studies have indicated that some lactic acid bacteria may effectively prevent or treat NAFLD. Overall, L. acidophilus KLDS1.0901 protected against HFD-induced NAFLD by improving liver characteristics and modulating microbiota composition, and thus could be a candidate for improving NAFLD. This study aimed to assess the protective effects of L. acidophilus KLDS1.0901 on a high-fat diet(HFD)-induced NAFLD. First, hepatic lipid profile and histological alterations were determined to study whether L. acidophilus KLDS1.0901 could ameliorate NAFLD. Then, the intestinal permeability and gut barrier were explored. Finally, gut microbiota was analyzed to elucidate the mechanism from the insights of the gut-liver axis. The results showed that Lactobacillus KLDS1.0901 administration significantly decreased body weight, Lee's index body, fat rate, and liver index. L. acidophilus KLDS1.0901 administration significantly improved lipid profiles by decreasing the hepatic levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) and by increasing the high-density lipoprotein cholesterol (HDL-C) levels. A conspicuous decrease of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum was observed after L. acidophilus KLDS1.0901 administration. Meanwhile, the H&E and Oil Red O-stained staining showed that L. acidophilus KLDS1.0901 significantly reduced liver lipid accumulation of HFD-fed mice by decreasing the NAS score and lipid area per total area. Our results showed that L. acidophilus KLDS1.0901 administration decreased the interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-alpha (TNF-α) concentrations accompanied by the increase of interleukin-10 (IL-10). L. acidophilus KLDS1.0901 administration could improve the intestinal barrier function by upregulating the mRNA levels of occludin, claudin-1, ZO-1, and Muc-2, which were coupled to the decreases of the concentration of LPS and D-lactic acid. Notably, L. acidophilus KLDS1.0901 administration modulated the gut microbiota to a near-normal pattern. Hence, our results suggested that L. acidophilus KLDS1.0901 can be used as a candidate to ameliorate NAFLD.
