Effects of Early Sub-Therapeutic Antibiotic Administration and its Subsequent Withdrawal on Body Composition, Gut Microbiota and Metabolite Profiles in a Pig Model

Abstract Background: Antibiotic exposure in early life has shown to be a significant risk factor for later fat accumulation in human. However, whether early sub-therapeutic antibiotic (STA) exposure affects body composition and its mechanisms remains unclear. The present study used a combination of comparative slaughter method, microbiota, and metabolomics measurement to investigate the effects of early STA administration and its subsequent withdrawal on body composition, colonic microbiota and metabolite profiles in a pig model. The piglets were fed the same basal starter diet added with STA (STA) or without STA (CON) for two weeks during the administration period, and then all piglets were switched to the same nursery diet without STA during the withdrawal period until they reached approximately 25 kg body weight. Results: Results showed that STA did not significantly improve piglet growth performance during the administration period and the withdrawal period. Piglets treated with the STA had a lower body water deposition (g/d) during the withdrawal period, and tended to have increased body lipid deposition (g/d) during the withdrawal period and the whole period than CON group. It was found that STA was initially effective in decreasing the abundance of pathogenic bacteria during the administration period, such as Alloprevotella, Bacteroides, Solobacterium, and Sutterella. However, they could not continue the effect during the withdrawal period, leading to the rebound of pathogenic bacteria such as Alloprevotella and the increase of the abundance of other pathogenic bacteria like Oscillibacter. Remarkably, STA treatment decreased the abundance of Blautia that play a potential protective role against obesity either during the administration period or the withdrawal period. Metabolomic analysis indicated that STA mainly altered amino acid metabolism, lipid metabolism, and carbohydrate metabolism during the two periods. Furthermore, Spearman's correlation analysis showed that the gut microbiota was highly correlated with microbial metabolites changes. Conclusion: These results suggest that STA administration may alter tissue deposition through reshaping the gut microbiota and their metabolite profiles.