糖尿病药物那格列奈促进嗜酸乳杆菌生长的作用

The effect of diabetes drug Nateglinide on the growth of Lactobacillus acidophilus

目的系统评价糖尿病药物对乳杆菌属微生物生长的影响,并进一步探讨糖尿病药物促进乳杆菌属微生物生长的作用机制。方法利用体外纯培养法评估糖尿病药物对乳杆菌属微生物生长的影响,筛选出具有促进作用的“药菌组合”,并进一步采用非靶向代谢组学技术检测“药菌组合”培养液上清中的代谢物组;采用结晶紫染色法和RT-qPCR法分别检测特定乳杆菌生物膜形成和细菌素生物合成基因的表达。结果10种常见糖尿病药物对乳杆菌的生长主要表现为抑制作用,仅那格列奈可在低浓度下刺激嗜酸乳杆菌的生长,促进率达48.30%。“那格列奈―嗜酸乳杆菌组合”培养液上清中共注释到584种已知代谢物,其中差异代谢物有42个,主要富集在氨基酸代谢和生物合成、氨酰t-RNA生物合成和次生代谢产物生物合成等代谢通路上;同时,那格列奈还促进了嗜酸乳杆菌生物膜的形成以及增加了生物膜的黏附性,并上调细菌素合成结构基因的表达(t=2.373,P=0.033)。结论糖尿病药物对乳杆菌生长普遍具有抑制作用,但那格列奈可通过调节氨基酸代谢和生物合成、促进生物膜的分泌和细菌素的生物合成来刺激嗜酸乳杆菌的生长。

Objective To systematically review the effects of diabetes drugs on the growth of Lactobacillus microorganisms,and further explore the mechanism of diabetes drugs that significantly promote the growth of Lactobacillus microorganisms.Methods The effect of diabetes drugs on the growth of Lactobacillus was evaluated with in vitro pure culture method,and the"drug-bacteria combination"with significant promoting effect was screened.The metabolites in the supernatant of the"drug-bacteria combination"culture medium were further detected using non-targeted metabolomics technology.Crystal violet staining and RT-qPCR were used to detect the expression of specific Lactobacillus biofilm formation and bacteriocin biosynthesis genes,respectively.Results The growth of Lactobacillus was mainly inhibited by 10 common diabetes drugs.Only Nateglinide stimulated the growth of Lactobacillus acidophilus at low concentration,with a promotion rate of 48.30%.A total of 584 known metabolites were annotated in the supernatant of"Nateglinide-Lactobacillus acidophilus combination",among which 42 were differential metabolites.These differential metabolites were mainly enriched in metabolic pathways such as amino acid metabolism and biosynthesis,aminoacyl t-RNA biosynthesis and secondary metabolite biosynthesis.At the same time,Nateglinide also significantly promoted the formation of Lactobacillus acidophilus biofilm and increased the adhesion of biofilm,and up-regulated the expression of bacteriocin synthesis structural genes(t=2.373,P=0.033).Conclusion Diabetes drugs generally inhibit the growth of Lactobacillus,but Nateglinide can stimulate the growth of Lactobacillus acidophilus by regulating amino acid metabolism and biosynthesis,promoting the secretion of biofilm and bacteriocin biosynthesis.