Short-term exposure to antibiotics begets long-term disturbance in gut microbial metabolism and molecular ecological networks.

Abstract

Background: Antibiotic exposure can occur in medical settings and from environmental sources. Long-term effects of brief antibiotic exposure in early life are largely unknown.

Results: Post a short-term treatment by ceftriaxone to C57BL/6 mice in early life, a 14-month observation was performed using 16S rRNA gene-sequencing technique, metabolomics analysis, and metagenomics analysis on the effects of ceftriaxone exposure. Firstly, the results showed that antibiotic pre-treatment significantly disturbed gut microbial α and β diversities (P < 0.05). Both Chao1 indices and Shannon indices manifested recovery trends over time, but they didn't entirely recover to the baseline of control throughout the experiment. Secondly, antibiotic pre-treatment reduced the complexity of gut molecular ecological networks (MENs). Various network parameters were affected and manifested recovery trends over time with different degrees, such as nodes (P < 0.001, R² = 0.6563), links (P < 0.01, R² = 0.4543), number of modules (P = 0.0672, R² = 0.2523), relative modularity (P = 0.6714, R² = 0.0155), number of keystones (P = 0.1003, R² = 0.2090), robustness_random (P = 0.79, R² = 0.0063), and vulnerability (P = 0.0528, R² = 0.28). The network parameters didn't entirely recover. Antibiotic exposure obviously reduced the number of key species in gut MENs. Interestingly, new keystones appeared during the recovery process of network complexity. Changes in network stability might be caused by variations in network complexity, which supports the ecological theory that complexity begets stability. Besides, the metabolism profiles of the antibiotic group and control were significantly different. Correlation analysis showed that antibiotic-induced differences in gut microbial metabolism were related to MEN changes. Antibiotic exposure also caused long-term effects on gut microbial functional networks in mice.

Conclusions: These results suggest that short-term antibiotic exposure in early life will cause long-term negative impacts on gut microbial diversity, MENs, and microbial metabolism. Therefore, great concern should be raised about children's brief exposure to antibiotics if the results observed in mice are applicable to humans. Video Abstract.