Ammonia exposure causes the imbalance of the gut-brain axis by altering gene networks associated with oxidative metabolism, inflammation and apoptosis

Ammonia (NH3) is an acknowledged environment pollutant in atmosphere with irritating smell. Previous studies have shown that excessive NH3 has toxic effects on farm animals and humans. However, the detail toxicity mechanism of NH3 to pigs is still unknown so far. In order to clarify the mechanism of NH3 toxicity, we established a porcine exogenous NH3 poisoning model and assessed the effect of NH3 on the gut-brain axis by transcriptome sequencing, qRT-PCR validation, histological observation and chemical analysis. Our results showed that after 30 d of NH3 exposure, 578 DEGs and 407 DEGs were obtained in the hypothalamus and jejunum, respectively. These DEGs were enriched into Gene Ontology (GO) terms associated with inflammation, oxidative metabolism, and apoptosis, and the highly expressed genes among these DEGs were verified by qRT-PCR. The content of GSH and the activities of GSH-Px and SOD were significantly decreased, while MDA content was increased after NH3 exposure. CRF, SP, 5-HT and ghrelin content in serum elevated significantly. Furthermore, pathologic observation in the NH3 group revealed infiltration of lymphocytes in the hypothalamus and significant decrease of jejunal epithelial cells. Our results indicated that NH3 exposure could cause changes in transcriptional profiles, pathological damage, oxidative stress and brain-gut peptide of the pig jejunum and hypothalamus, and lead to the imbalance of the brain-gut axis through the 'oxidative stress-inflammation-apoptosis' interaction network. Our study not only provides a new perspective for the toxicity assessment of NH3, but also enriches the toxicology mechanism of NH3.