中等海拔低压低氧环境暴露对中国健康人群肠道菌群的影响

Effects of moderate-altitude exposure on intestinal flora of Chinese healthy population

目的:分析中等海拔低压低氧环境暴露对健康人群肠道菌群的影响。方法:招募2018年~2019年由广东省广州市(平均海拔<50 m)派驻西藏林芝市八一区(平均海拔约2900 m)进行援藏建设工作的健康成人,基线组(base组)42例,入藏6个月组(暴露组,six组)34例。收集人群的粪便样本,提取肠道微生物DNA,对肠道菌群16S rDNA V3~V4区进行高通量测序并进行生物信息学分析。结果:(1)两组人群门水平的优势菌类别相同,但门、属菌群比例不同。与base组相比,暴露组菌群α多样性增加(P=4.00×10^(-4)),β多样性下降(P=1.00×10^(-3)),菌群分布存在显著差异。(2)差异分析显示,与base组相比,six组与代谢综合征发生、机体炎症正相关的变形菌门(Pro-teobacteria)(|LDA|>4,P<0.05),有害菌埃希氏-志贺氏菌属(Escherichia-Shigella)、粪肠球菌(Enterococcus_faecalis)、流感嗜血杆菌(Haemophilus_influenzae)和幽门螺杆菌(Helicobacter_sp._UNSW1.7sp)丰度下降(adjusted P<0.05);而拟杆菌门(Bacteroidetes)(|LDA|>4,P<0.05),有益菌丁酸梭菌属(Butyricimonas)、乳酸杆菌[Lactobacillus_sp._RA2113(s)]和丁酸梭菌[Butyricimonas_sp._Marseille-P2440(s)]丰度增加(adjusted P<0.05)。(3)PICRUSt功能预测显示,中等海拔低压低氧暴露后的人群肠道菌群外源物质生物降解与代谢、膜运输、氨基酸代谢功能显著性降低(adjusted P<0.05),其它次生代谢物的生物合成、核苷酸代谢功能显著性增强(adjusted P<0.05)。(4)BugBase表型预测分析表明,中等海拔低压低氧环境暴露后人群的肠道菌群表型发生显著变化,与base组相比,six组革兰氏染色阳性菌和厌氧菌的比例增加(adjusted P<0.05);革兰氏染色阴性、兼性厌氧、氧化胁迫耐受和生物膜形成特征的菌比例下降(adjusted P<0.05)。结论:中等海拔低压低氧暴露后健康人群肠道菌群组成及多样性改变;菌群门、属水平的物种丰度发生变化;肠道菌群的功能基因丰度存在显著差异,表明中等海拔低压低氧暴露对人体肠道菌群存在一定影响。

AIM:To explore the effects of moderate-altitude exposure on intestinal flora in healthy individuals.METHODS:The aid-Tibet cadres,who were sent to work from Guangdong(average altitude<50 m)to Nyingchi(average altitude of 2900 m),were recruited.A total of 76 samples were collected,including 42 samples from healthy adults with plateau living for 0 day and 34 samples from healthy adults with plateau living for 6 months.Fecal samples DNA were ex-tracted,sequenced by the 16S rDNA high-throughput sequencing technology and analyzed bioinformatically.RESULTS:Compared with the base group,αdiversity was increased(P=4.00×10^(-4))andβdiversity was decreased(P=1.00×10^(-3)).After moderate altitude exposure,the relative abundance of phylum Proteobacteria(|LDA|>4,P<0.05),genus Escherich-ia-Shigella,species Enterococcus_faecalis,Haemophilus_influenzae and Helicobacter_sp._UNSW1.7sp decreased(adjust-ed P<0.05),wheras the relative abundance of phylum Bacteroidetes(|LDA|>4,P<0.05),genusButyricimona,species Lactobacillus_sp._RA2113(s)and Butyricimonas_sp._Marseille-P2440(s)increased(adjusted P<0.05).The function-al prediction by PICRUSt showed a decrease in the relative abundance of pathway related to xenobiotics biodegradation and metabolism,membrane transport and amino acid metabolism(adjusted P<0.05).Conversely,the relative abundance of pathway related to biosynthesis of other secondary metabolites and nucleotide metabolism was increased(adjusted P<0.05).Finally,the results of microbiome phenotype prediction by BugBase showed that moderate altitude exposure im-proves the gut microbiota functions involving anaerobic oxygen tolerance and gram positive(adjusted P<0.05).And bacte-ria containing facultatively anaerobic oxygen tolerance,oxidative stress tolerance,gram negative and biofilm formation in the six-group decreased significantly compared with those in base group(adjusted P<0.05).CONCLUSION:Moderate altitude exposure impacts the diversity,abundance and function of intestinal flora in healthy population,suggesting that al-titude factors may have some influence on gut microbiota.