The Gut-brain Axis In Antibiotic-induced Disruption Of Gut Microbiota

Antibiotics are commonly prescribed drugs for bacterial infections in clinic,while long-term antibiotic use has been reported to exert collateral effects on gut microbiota composition and functionality within the host,which further lead to metabolic disorders,inflammatory diseases and impair brain development and functions as well.However,little is known about the implications of acute antibiotic use on gut health,microbiota,and the brain functions,as well as the underlying mechanisms.Our current work aims to investigate the transcriptional regulation within the gut and brain of the host induced by one-time high dose antibiotics with the mouse model,and trying to modulate the antibiotic effect with fecal microbiota transplantation(FMT).The results showed that one-time antibiotic(ampicillin,vancomycin,neomycin,metronidazole)treatment could induce dramatic decrease in the gut microbiota of the mice,which could last for 6-8 weeks,indicating long-term antibiotic treatment could exert lasting and severe effects on the host.Compared to the aged mice,the disruption induced by low dose antibiotic treatment could be recovered more quickly,indicating the age-related recovery competence in the gut microbiota and functions.Then,we investigated the transcriptional changes of certain brain regions 24 hours after one-time antibiotic treatment to explore the underlying mechanisms of gut-brain axis induced by antibiotic use.We collected tissues from the hippocampus,striatum,cerebellum as well as the proximal colon for transcription analysis.These specific brain regions have been shown to play important roles in cognition and emotions,and proximal colon receives massive neural control from the brain.Our results presented differentially expressed genes(DEGs)profiles which were diverse among regions/organs one day after antibiotic treatment.Most of the DEGs were only presented in certain single tissue,such as most of DEGs in the colon of young mice and in the striatum of aged mice and KEGG pathways mainly in the aged mice.The neuroactive ligand-receptor interaction pathway was shared in the colon and cerebella,indicating close relationship between them.Finally,we investigated the age difference between recipients and donors in the recovery to explore the beneficial effects on the gut microbiota and the transcriptome of the proximal colon.The results showed that FMT could facilitate the recovery of the gut microbiota,such as the increase in Muribaculaceae and the decrease in EsherichiaShigella.Transcriptional changes of the proximal colon could be seen in Gsdmc genes,associated with cell membrane permeability.Taken together,these data provide further understanding of the regulatory mechanisms of the host related to gut-brain axis implicated by antibiotic use.Further researches are needed to uncover the mechanisms in the long-term effects on the brain transcriptome and whether FMT could facilitate the recovery in regard of transcriptional changes of the brain by antibiotics.