| Objective: To investigated the structure and diversity of the intestinal flora in rats exposed to high altitude hypoxia.To predicted the phenotypic abundance and gene functional of the intestinal flora in rats exposed to high altitude hypoxia.To clarified the relationship between intestinal flora and high altitude hypoxia.The project provide a theoretical basis for further research on the initiation and development of diseases and drug metabolism under high altitude hypoxia.Methods: 24 SPF male SD rats were randomly divided into the control group,the moderate altitude hypoxia group and the high altitude hypoxia group.The p H value of feces and peripheral blood of rats were measured.The pathological morphological changes of kidney,liver and small intestine were observed by HE staining.The plasma concentration of HIF-1?,TNF-?,IL-1?,IL-4,IL-6,and IL-10 were detected by ELISA.The structure of intestinal flora of rats were characterized by 16 S r DNA high-throughput sequencing technology.The Alpha and Beta diversity of the intestinal flora of rats were analyzed,and the phenotypic abundance and gene function were predicted by bioinformatics.Results: Compared with the control group,the p H value of feces of rats were significantly decreased in the moderate altitude hypoxia group and the high altitude hypoxia group.The value of HGB,MCV and MCH were significantly increased by 9.55%,8.78% and 6.97%,respectively,and the WBC and MPV were significantly decreased by 54.81% and 14.77% in the moderate altitudes hypoxia group,respectively,than that in the control group.The value of RBC,HGB and MCHC were significantly increased by 7.69%,11.76% and 11.96%,respectively,and the WBC and MCV were significantly decreased by 50.76% and 7.10%,respectively,than that in the control group.Compared with the control group,the pathological morphology of kidney,liver and small intestinal of rats in the moderate altitude hypoxia group had no significant change as well as the kidney and liver in the high altitude hypoxia group.The capillary of lamina propria of the small intestine mucosa were slightly dilated.The concentration of HIF-1? in plasma of rats was increased,and the concentration of TNF-?,IL-1?,IL-4,IL-6 and IL-10 were decreased in the moderate altitude hypoxia group,but there was no statistical significance,compared with the control group.The concentrations of TNF-?and IL-6 were increased,and the concentration of IL-1? and IL-10 were decreased in the high altitude group than that in the control group,but there was no statistical significance.The concentration of HIF-1? was significantly increased by 171.30%,and the concentration of IL-4 was significantly decreased in the high altitude group by 25.51%,compared with the control group.The results showed that the structure of intestinal flora of rats significantly changed on the 30 th day under high altitude hypoxia environment.A total of 34 phylum,80 classes,196 orders,314 families,574 genus,and 208 species were annotated in three groups of rats,including Firmicutes,Bacteroidetes,Bacteroidia,Muribaculaceae,Lactobacillus and Lactobacillus?murinus.The indicator species were Microflora Verrucomicrobia and Akkermansia in the control group.The indicator species were Spirochaetes and Treponema?2 in the moderate altitude hypoxia group,and the indicator species were Patescibacteria and Eubacterium?coprostanoligenes?group in the high altitude hypoxia group.A total of 33 different microbiota of gut microorganisms were detected on the 30 days under hypoxia,there were 10 different microbiota of gut microorganisms with higher relative abundance in the control group,of which SAR86?clade bacteria was the most commont.There were 11 different microbiota of gut microorganisms with higher relative abundance in the moderate altitude hypoxia group,of which Prevotellaceae?UCG?003 bacteria was the most common.There were 12 different microbiota of gut microorganisms with higher relative abundance in the high altitude hypoxia group,of which Lactobacillus?gasseri bacteria was the most common.The results of the Alpha diversity of the intestinal flora showed that the amount of sequencing tends to be saturated,which can basically reflect the diversity of the intestinal flora of the three groups of rats.The moderate altitude hypoxia group and high altitude hypoxia group displayed higher richness,lower uniformity,and lower diversity of intestinal flora of rats,compared with the control group.The results of Beta diversity analysis showed that there were significant differences of the microbial structure of rats in different groups.The similarity of intestinal flora of rats in the same group is higher,and vice versa.The prediction of phenotypic abundance showed that the aerobic,mobile element containing and gram negative exhibited higher phenotypic abundance in the control group.The anaerobic,gram positive and pathogenic exhibited higher phenotypic abundance in the moderate altitude hypoxia group.The pathogenic,facultatively anaerobic and oxidative stress tolerant exhibited higher phenotypic abundance in the high altitude hypoxia group.The prediction of gene function showed that the intestinal flora of rats were mainly involved in the process of pantothenate and Co A biosynthesis,ABC transporter transport,PPAR signaling pathway,etc,in the control group.The gene functions of the intestinal flora of rats were mainly involved in the RNA transport,oxidative phosphorylation,glycosaminoglycan degradation,etc,in the moderate altitude hypoxia group.The gene functions of the intestinal flora of rats were mainly involved in the pentose phosphate pathway,drug metabolism cytochrome P450,MAPK signaling pathway,etc,in the high altitude hypoxia group.Conclusion: The high altitude hypoxia environment caused certain damage to the intestinal tract by affecting the p H value of feces,peripheral blood,cytokines and small intestinal histomorphology in rats.At the same time,the high altitude hypoxia environment altered the structure and diversity of the intestinal flora of rats,which mainly manifested in increasing of the relative abundance of anaerobic bacteria and pathogenic bacteria in the indicator species and different microbiota of gut microorganisms.This result lead to the change of phenotypic abundance and gene function prediction of intestinal flora.The research indicated the relationship of the intestinal flora with high altitude hypoxia,and provided the possibility to study the mechanism of intestinal flora mediated high altitude hypoxia environment affecting drug metabolism. |
PDF Full Text Request