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Early-life vancomycin treatment promotes airway inflammation and impairs microbiome homeostasis.

ABSTRACT: Several studies have reported that gut and lung microbiomes are involved in the process of asthma pathogenesis. However, it remains unclear how perinatal or early-life antibiotic intervention affect adult allergic airway inflammation. We assigned C57BL/6 mice randomly to four experimental groups: normal saline control (NS), ovalbumin (OVA), vancomycin pretreated NS (VAN-NS), and vancomycin pretreated OVA (VAN-OVA). The vancomycin groups were orally given the drug from gestational day 14 to 6 week. An OVA-induced asthma model was then established at 6 weeks of age, and airway inflammation was evaluated. In addition, total DNA was extracted from the feces and lung tissue and used for 16S rDNA gene sequencing, to detect the composition of the microbiome. In the VAN-OVA group, airway inflammation and Th2-related cytokines were found to be significantly increased versus the control groups. Gene sequencing showed that vancomycin treatment attenuated the richness and evenness, and altered the composition of the microbiome in the gut and lung. Micrococcaceae and Clostridiaceae-1 were potentially correlated to the severity of allergic airway inflammation. Our study suggests that perinatal and early-life vancomycin intervention aggravates allergic inflammation in adulthood, which might be correlated with imbalanced gut and lung microbiome homeostasis.

SUBMITTER: Yang X

PROVIDER: S-EPMC6503881 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Early-life vancomycin treatment promotes airway inflammation and impairs microbiome homeostasis.

Yang Xin X Feng Hanrong H Zhan Xueqin X Zhang Chao C Cui Rui R Zhong Lijia L Ying Songmin S Chen Zhimin Z

Aging 20190401 7

Several studies have reported that gut and lung microbiomes are involved in the process of asthma pathogenesis. However, it remains unclear how perinatal or early-life antibiotic intervention affect adult allergic airway inflammation. We assigned C57BL/6 mice randomly to four experimental groups: normal saline control (NS), ovalbumin (OVA), vancomycin pretreated NS (VAN-NS), and vancomycin pretreated OVA (VAN-OVA). The vancomycin groups were orally given the drug from gestational day 14 to 6 wee ...[more]

PMID: 30981206

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Project description:BackgroundChromodomain helicase DNA-binding protein 8 (Chd8) is a high-confidence risk gene for autism spectrum disorder (ASD). However, how Chd8 haploinsufficiency impairs gene expression in the brain and impacts behavior at different stages of life is unknown.MethodsWe generated a mutant mouse line with an ASD-linked loss-of-function mutation in Chd8 (V986*; stop codon mutation). We examined the behavior of Chd8 mutant mice along with transcriptional changes in the cerebral cortex as a function of age, with a focus on one embryonic (E14.5) and three postnatal ages (1, 6, and 12 months).ResultsChd8V986*/+ mutant mice displayed macrocephaly, reduced rearing responses and reduced center time in the open field, and enhanced social novelty preference. Behavioral phenotypes were more evident in Chd8V986*/+ mutant mice at 1 year of age. Pup survival was reduced in wild-type x Chd8V986*/+ crosses when the mutant parent was female. Transcriptomic analyses indicated that pathways associated with synaptic and neuronal projections and sodium channel activity were reduced in the cortex of embryonic Chd8V986*/+ mice and then equalized relative to wild-type mice in the postnatal period. At 12 months of age, expression of genes associated with endoplasmic reticulum (ER) stress, chaperone-mediated protein folding, and the unfolded protein response (UPR) were reduced in Chd8V986*/+ mice, whereas genes associated with the c-MET signaling pathway were increased in expression.LimitationsIt is unclear whether the transcriptional changes observed with age in Chd8V986*/+ mice reflect a direct effect of CHD8-regulated gene expression, or if CHD8 indirectly affects the expression of UPR/ER stress genes in adult mice as a consequence of neurodevelopmental abnormalities.ConclusionsCollectively, these data suggest that UPR/ER stress pathways are reduced in the cerebral cortex of aged Chd8V986*/+ mice. Our study uncovers neurodevelopmental and age-related phenotypes in Chd8V986*/+ mice and highlights the importance of controlling for age when studying Chd8 haploinsufficient mice.

Dataset Information

Early-life vancomycin treatment promotes airway inflammation and impairs microbiome homeostasis.

Publications

Early-life vancomycin treatment promotes airway inflammation and impairs microbiome homeostasis.

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