Leech Poecilobdella manillensis protein extract ameliorated hyperuricemia by restoring gut microbiota dysregulation and affecting serum metabolites

BACKGROUND Hyperuricemia(HUA)is a public health concern that needs to be solved urgently.The lyophilized powder of Poecilobdella manillensis has been shown to significantly alleviate HUA;however,its underlying metabolic regulation remains unclear.AIM To explore the underlying mechanisms of Poecilobdella manillensis in HUA based on modulation of the gut microbiota and host metabolism.METHODS A mouse model of rapid HUA was established using a high-purine diet and potassium oxonate injections.The mice received oral drugs or saline.Additionally,16S rRNA sequencing and ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry-based untargeted metabolomics were performed to identify changes in the microbiome and host metabolome,respectively.The levels of uric acid transporters and epithelial tight junction proteins in the renal and intestinal tissues were analyzed using an enzyme-linked immunosorbent assay.RESULTS The protein extract of Poecilobdella manillensis lyophilized powder(49 mg/kg)showed an enhanced anti-trioxypurine ability than that of allopurinol(5 mg/kg)(P<0.05).A total of nine bacterial genera were identified to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder,which included the genera of Prevotella,Delftia,Dialister,Akkermansia,Lactococcus,Escherichia_Shigella,Enterococcus,and Bacteroides.Furthermore,22 metabolites in the serum were found to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder,which correlated to the Kyoto Encyclopedia of Genes and Genomes pathways of cysteine and methionine metabolism,sphingolipid metabolism,galactose metabolism,and phenylalanine,tyrosine,and tryptophan biosynthesis.Correlation analysis found that changes in the gut microbiota were significantly related to these metabolites.CONCLUSION The proteins in Poecilobdella manillensis powder were effective for HUA.Mechanistically,they are associated with improvements in gut microbiota dysbiosis and the regulation of sphingolipid and galactose metabolism.

Potential of traditional Chinese medicine lyophilized powder of Poecilobdella manillensis in the treatment of hyperuricemia

Traditional Chinese medicine has a long and illustrious history,and with the development of modern science and technology,the research and application of traditional Chinese medicines have continued to progress significantly.Many traditional Chinese medicinal herbs have undergone scientific validation,reinvi-gorating with new life and vitality,and contributing unique strengths to the advancement of human health.Recently,the discovery that leech total protein extracted from Poecilobdella manillensis lyophilized powder reduces blood uric acid(UA)levels by inhibiting the activity of xanthine oxidase to decrease UA synthesis and promotes UA excretion by regulating different UA transporters in the kidney and intestine has undoubtedly injected new vitality and hope into this field of research.The purpose of this editorial is to comment on this study,explore its strengths and weaknesses,and there is a hope to treat a range of metabolic-related syndromes,including hyperuricemia,by targeting the gut microbiota.