The Mitigative Effects Of Blautia Producta On The Acute Inflammation Induced By Lipopolysaccharide And Its Safety Research

Blautia is a genus of anaerobic microorganism incluing 20 species which occurs widely in the intestines and feces of mammals.Recently,studies have shown that the amelioration effects of Blautia on inflammatory and metabolic diseases were strongly associated with its relative abundance.However,direct evidence for specific efficacy of Blautia is still lacking.Few studies have assessed the genome of Blautia and comparative genomic analysis of Blautia has not been performed.Therefore,it is necessary to understand the strain characteristics from the genome.In this study,we performed comparative genomic analysis of Blautia to elucidate the correlation between probiotic properties and genes,explored its alleviating effect on acute inflammation by constructing a lipopolysaccharide(LPS)induced acute inflammation model,further combined with a comprehensive safety assessment to lay the theoretical foundation for the development of novel functional microorganisms with probiotic properties.The main results are as follows:Comparative genomic analysis revealed that Blautia genomes differ greatly between species;Blautia has an open genome with the largest proportion of core gene functions for translation,ribosome structure and biosynthesis;clusters of genes responsible for NRPs and Sactipeptide biosynthesis are present in all Blautia strains.B.producta D4 was isolated from mouse feces,which possessed a faster growth rate and stronger acid production capacity in GAM medium.Acute inflammation model was constructed by intraperitoneal injection of LPS(5 mg/kg)to evaluate the alleviating effects of B.producta on acute inflammation.The results showed that B.producta D4 and B.producta DSM2950 could alleviate inflammation by reducing the levels of inflammatory factors(TNF-?,IL-1? and IL-6),increasing the levels of short-chain fatty acids and regulating the structure of the intestinal microbiota.The intervention of both B.producta strains reduced LPS-induced damage in liver,lung,and colon tissue,especially the acute liver injury.Further analysis revealed that B.producta D4 and B.producta DSM2950 could alleviate liver injury by decreasing the levels of ALT and AST,increasing the activities of antioxidant enzymes in liver tissue,and decreasing the transcript levels of inflammation and apoptosis-related genes and protein levels of key regulators(TLR4,My D88 and Caspase-3).Most of the virulence genes identified by B.producta are related to regulation and iron ion uptake;in both strains of B.producta D4 and B.producta DSM2950,one gene island carrying a toxin gene and 9 different types of antibiotic resistance genes were identified.The in vitro experiment concluded that the strains were not hemolytic and sensitive to most of the antibiotics tested.The results of the acute toxicity test showed that different doses of B.producta strains had no side effect on body weight,food intake,water intake and organ index of mice,and the hematogical and biochemical parameters did not show the significant differences from the control group.In addition,histopathology of mice liver,spleen and kidney showed no abnormal changes,indicating that B.producta is safe.