Distinctive gut antibiotic resistome, potential health risks and underlying pathways upon cerebral ischemia-reperfusion injury.

Antibiotic resistance genes (ARGs) as emerging pollutants pose health risks to humans and the environment. Gut microbiota is an important reservoir for ARGs and hotspot for ARG acquisition and dissemination. Non-antibiotic factors (such as disease pathophysiology) affect ARG emergence and dissemination. Cerebral ischemia-reperfusion injury (I/R) commonly occurs in stroke patients. However, effects of I/R on ARG emergence and dissemination are unknown. Therefore, metagenomics was used to unveil selective collection of gut antibiotic resistome and its health risks, key ARG hosts and underlying pathways upon I/R. Changes in gut antibiotic resistome upon I/R were characterized by tetracycline ARG accumulation and decreases in aminoglycoside and glycopeptide ARGs. Besides, changes in gut antibiotic resistome were corrected with those in gut microbiota from phylum to species, serum lipid accumulation and glucose depletion upon I/R. Additionally, health risks of gut microbial multidrug ARGs (such as abem, adek and TolC), macA, aph(3')-I and carO, co-localized with mobile gene elements, were increased upon I/R. Moreover, phyla Firmicutes (especially order Eubacteriales, class Clostridia) and Bacteroidota were key ARG hosts in gut microbiota of I/R gerbils. Furthermore, suppression of vancomycin resistance, and lantibiotic biosynthesis and immunity, disturbances in peptidoglycan biosynthesis and hydrolysis, activation of antimicrobial peptide resistance, lipopolysaccharide biosynthesis, teichoic acid biosynthesis, arabinogalactan biosynthesis, aromatic compound degradation, oxidative phosphorylation, the tricarboxylic acid cycle and its anaplerotic pathways were observed in upon I/R. This study provides novel insights and intervention targets related to selective collection of gut antibiotic resistome and its potential health risks upon I/R.