Faecal microbiota transplantation alleviates early-life antibiotic-induced gut microbiota dysbiosis and mucosa injuries in a neonatal piglet model.

Faecal microbiota transplantation (FMT) is a promising approach to modulate the gut microbiota. Gut microbiota dysbiosis caused by antibiotic administration is a universal problem. This study aimed to evaluate the effect of FMT on the dysbiosis of gut microbiota and metabolic profiles and injury of the intestinal barrier induced by antibiotics and used a neonatal piglet model. Neonatal piglets were administered ampicillin for 3 days, and antibiotic-induced dysbiosis was evaluated by the occurrence of diarrhoea and alteration of gut microbiota. Then, FMT was conducted for 3 days to rebuild the gut microbiota. High-throughput sequencing and a mass spectrometry platform were used for integrated microbiome-metabolome analysis. The results showed that antibiotics led to a decline in the diversity of gut microbiota. Furthermore, there was an increase in the relative abundance of potential pathogenic bacteria, such as Oscillibacter, Pseudomonas and Eubacterium, and an increase in the relative abundance of tetracycline resistance genes (tet genes). FMT restored the diversity and promoted the relative abundance of beneficial bacteria, such as Parabacteroides, Dorea and Parasutterella, while decreasing the relative abundance of tet genes. Untargeted metabolomics analysis found that alpha linolenic acid and linoleic acid metabolism were the key metabolic pathways utilized in the FMT group, and targeted metabolomics analysis further verified the variation in the associated metabolites arachidonic acid and conjugated linoleic acid. FMT also significantly enhanced the relative expression of tight junction (ZO-1, claudin-1 and occludin) and adherens junction (β-catenin, E-cadherin) proteins and anti-inflammatory cytokines (IL-10, TGF-β1) and reduced the production of proinflammatory cytokines (IL-6, IL-1β, TNF-α and IFN-γ) in the colon. FMT not only modulated the gut microbiota composition and microbial metabolism but also reduced the relative abundance of tet genes, improving the intestinal barrier function and inflammatory responses in antibiotic-treated piglets.