Intestinal microbiota dysbiosis and liver metabolomic changes during brain death

Background Whether a causative link exists between brain death(BD)and intestinal microbiota dysbiosis is unclear,and the distortion in liver metabolism associated with BD requires further exploration.Methods A rat model of BD was constructed and sustained for 9 h(BD group,n=6).The sham group(n=6)underwent the same procedures,but the catheter was inserted into the epidural space without ballooning.Intestinal contents and portal vein plasma were collected for microbiota sequencing and microbial metabolite detection.Liver tissue was resected to investigate metabolic alterations,and the results were compared with those of a sham group.Resultsα-diversity indexes showed that BD did not alter bacterial diversity.Microbiota dysbiosis occurred after 9 h of BD.At the family level,Peptostreptococcaceae and Bacteroidaceae were both decreased in the BD group.At the genus level,Romboutsia,Bacteroides,Erysipelotrichaceae_UCG_004,Faecalibacterium,and Barnesiella were enriched in the sham group,whereas Ruminococcaceae_UCG_007,Lachnospiraceae_ND3007_group,and Papillibacter were enriched in the BD group.Short-chain fatty acids,bile acids,and 132 other microbial metabolites remained unchanged in both the intestinal contents and portal vein plasma of the BD group.BD caused alterations in 65 metabolites in the liver,of which,carbohydrates,amino acids,and organic acids accounted for 64.6%.Additionally,80.0%of the differential metabolites were decreased in the BD group livers.Galactose metabolism was the most significant metabolic pathway in the BD group.Conclusions BD resulted in microbiota dysbiosis in rats;however,this dysbiosis did not alter microbial metabolites.Deterioration in liver metabolic function during extended periods of BD may reflect a continuous worsening in energy deficiency.

Uncover landfilled antimicrobial resistance:a critical review of antibiotics flux,resistome dynamics and risk assessment

Municipal solid waste(MSW)landfill is one of the most important reservoirs of antimicrobial resistance(AMR)in urban environments.By reviewing~120 published cases worldwide,we found that leachate-borne antibiotics were at theμg/L level,and meanwhile,around 8 tons of antibiotics(including the clinically relevant ones)annually leached from the MSW landfills in China.During a decade-long landfilling process,the leachate-borne bacteria mainly originating from humanassociated waste(>40%)formed a community network being versatile to the drastic environmental changes.Among them,the keystone species(Proteobacteria subtaxa)functioned for metabolizing the most available substrate in leachates and were also the hosts of mobile antibiotic resistance genes(ARGs),which suggested the enduring and close associations between bacterial community and resistome.These leachate-borne ARGs were highly mobile via plasmid-mediated horizontal gene transfer,especially in less aged leachates(<10 yr).MetaCompare showed that the AMR-hazard index of landfill-specific airborne particles(index=20.5)was significantly higher than that of drinking water(index=17.81,P<0.01).Human daily exposure of ARGs amounted to an inhalation of(5.83±0.16)×105 copies of ARGs,being tenfold higher than that ingestion of drinking water,which implies landfills as a non-ignorable AMR source.