Effects Of Environmental Microbial Exposure In Early Life On Colonization Of Gut Microbiota And Immunity And Metabolism In Adulthood

This study intends to exploit high-throughput sequencing technology to analyze the different environmental microbial exposure and the colonization of gut microbiota in infants of one-month old both in urban and rural,and to explore the potential impact of different environmental microbial exposure on the colonization of infant gut microbiota.The microbial exposure models in different environments in early life were established to investigate the effects of microbial exposure in different stages and environments in early life on gut microbiota colonization via high-throughput sequencing technology,serum cytokines IFN-? and IL-4 level with ELISA which reflect immune function(Th1/Th2 balance)and the quantity of short-chain fatty acids(SCFAs)in BALB/c offspring during adulthood by gas chromatography.To explore the possible protective mechanism and “window of opportunity” of early life environmental microbial exposure which may provide a new method and theoretical basis for the prevention and treatment of allergic diseases such as asthma.The main results of this research are as follows:1.The different effects of microbial exposure on gut microbiota colonization in early period of infants who lived in urban and rural environments respectively.1)The colony abundance indices of Chao1 and ACE of rural group were higher than those of urban group.There were significant differences in bacterial community structure between the two groups.There was no significant difference between the two groups in the dominant phylum.LEf Se analysis showed that the dominant bacteria of microbial community in urban dust are Staphylococcus,Corynebacterium,Kocuria and Propionibacterium,while Psychrobacter,Massilia,Pseudoalteromonas,Salinivibrio are the dominant bacteria in rural dust.2)There were no significant differences in the dominant phylum,bacterial community diversity and structure between rural and urban groups.LEf Se analysis showed that the dominant bacteria in urban infants' feces were Clostridium,Lachnoclostridium and Comamonas.The dominant bacteria in rural group's feces were Chrysobacterium,Eisenbergiella,Betaproteobacteria,Lactococcus and Vibrio.3)Microflora diversity in environment were significantly higher than those in infant gut microbiota.However,Spearman correlation analysis investigated that there was no significant difference between environmental microbiota and gut microbiota.There are certain differences of dominant bacteria(at the level of phylum and genus)between the living environment and the gut of infants.The relative abundance of Proteobacteria in infant gut was positively correlated with that of the environment and negatively correlated with that of Cyanobacteria.The relative abundance of Streptococcus,Chloroplast-norank,Enterococcus,Escherichia-Shigella,Clostridium and Acinetobacter in infant gut microbiota was negatively correlated with that of environment.Source Tracker analysis showed that 65.77% of the gut microbiota in infants came from environmental microorganisms.In addition,gut microbiota from environmental microorganisms accounts for 76.43% in urban group and 55.10% in rural group,respectively.2.Effects of environmental microbial exposure in early life on gut microbiota colonization,immunity and metabolic function in offspring BALB/c mice.The results illustrated that there were significant differences in the composition and structure of gut microbiota in adulthood of BALB/c mice which exposed to microbial rich environment e in the different early stages of life.When continuously exposed to relatively "clean" environment,the relative abundance of Verrucomicrobia,Actinobacteria,Staphylococcus and Bifidobacterium was markedly increased.The relative abundance of Dorea increased significantly in adulthood when continuously exposed to relatively "dirty" environment in rich of microbial.The relative abundance of Corynebacterium and Akkermansia as significantly higher in adulthood when exposed to "clean" environments before breast feeding.The relative abundance of unclassified genus from Lachnospiraceae families,Adlercreutzia and Lactobacillus ruminis were obviously increased after adolescence when exposed to "dirty" environments since lactation period.In addition,persistent and abundant exposure to microbial environment could increase the production of IFN-?(Th1 type cytokines)and intestinal metabolites SCFAs in adulthood.These findings suggest that the dynamic interaction between environmental microorganisms and host gut microbiota in the early stages of life has a profound impact on the composition of gut microbiota,host immune function and intestinal metabolites in adulthood.In summary,there were remarkable differences in microbial exposure between urban and rural living environments in China,which have no obvious influence in diversity and structure of infants' gut microbiota in early life.Proteobacteria in the environment could affect the colonization of Proteobacteria in the gut during the early period of infants.In the urban environment,the proportion of gut microbiota from environmental microbes was higher than that of the rural environment.Early environmental microbial exposure during infant period can affect the diversity and structure of gut microbiota in adult mice,resulting in certain differences in composition of gut microbiota.The lower the environmental cleanliness was,the higher the diversity of gut microbiota was.Due to early environmental microbial exposure,Th0 could be induced to Th1,affecting the balance of Th1/Th2.Additionally,the reduction of SCFAs produced by gut microbiota would be found in adult rats which ever exposed under environmental microbial.In general,fetal and breast-feeding period may be important " window of opportunity " for gut microbiota colonization.