PDF(Pubmed)
Abstract：
D-amino acids, the chiral counterparts of protein L-amino acids, were primarily produced and utilized by microbes, including those in the human gut. However, little was known about how orally administered or microbe-derived D-amino acids affected the gut microbial community or gut disease progression.
The ratio of D- to L-amino acids was analyzed in feces and blood from patients with ulcerative colitis (UC) and healthy controls. Also, composition of microbe was analyzed from patients with UC. Mice were treated with D-amino acid in dextran sulfate sodium colitis model and liver cholangitis model.
The ratio of D- to L-amino acids was lower in the feces of patients with UC than that of healthy controls. Supplementation of D-amino acids ameliorated UC-related experimental colitis and liver cholangitis by inhibiting growth of Proteobacteria. Addition of D-alanine, a major building block for bacterial cell wall formation, to culture medium inhibited expression of the ftsZ gene required for cell fission in the Proteobacteria Escherichia coli and Klebsiella pneumoniae, thereby inhibiting growth. Overexpression of ftsZ restored growth of E. coli even when D-alanine was present. We found that D-alanine not only inhibited invasion of pathological K. pneumoniae into the host via pore formation in intestinal epithelial cells but also inhibited growth of E. coli and generation of antibiotic-resistant strains.
D-amino acids might have potential for use in novel therapeutic approaches targeting Proteobacteria-associated dysbiosis and antibiotic-resistant bacterial diseases by means of their effects on the intestinal microbiota community.
The ratio of D- to L-amino acids was analyzed in feces and blood from patients with ulcerative colitis (UC) and healthy controls. Also, composition of microbe was analyzed from patients with UC. Mice were treated with D-amino acid in dextran sulfate sodium colitis model and liver cholangitis model.
The ratio of D- to L-amino acids was lower in the feces of patients with UC than that of healthy controls. Supplementation of D-amino acids ameliorated UC-related experimental colitis and liver cholangitis by inhibiting growth of Proteobacteria. Addition of D-alanine, a major building block for bacterial cell wall formation, to culture medium inhibited expression of the ftsZ gene required for cell fission in the Proteobacteria Escherichia coli and Klebsiella pneumoniae, thereby inhibiting growth. Overexpression of ftsZ restored growth of E. coli even when D-alanine was present. We found that D-alanine not only inhibited invasion of pathological K. pneumoniae into the host via pore formation in intestinal epithelial cells but also inhibited growth of E. coli and generation of antibiotic-resistant strains.
D-amino acids might have potential for use in novel therapeutic approaches targeting Proteobacteria-associated dysbiosis and antibiotic-resistant bacterial diseases by means of their effects on the intestinal microbiota community.
摘要：
目标：D-氨基酸，蛋白质L-氨基酸的手性对应物，主要由微生物产生和利用，包括人类肠道中的那些。然而,我们对口服或微生物来源的D-氨基酸如何影响肠道微生物群落或肠道疾病进展知之甚少.
方法：分析溃疡性结肠炎（UC）患者和健康对照者的粪便和血液中D-与L-氨基酸的比例。此外，分析了UC患者的微生物组成。用D-氨基酸处理小鼠右旋糖酐硫酸钠结肠炎模型和肝胆管炎模型。
结果：UC患者粪便中D-与L-氨基酸的比例低于健康对照组。补充D-氨基酸通过抑制变形杆菌的生长改善UC相关的实验性结肠炎和肝胆管炎。添加D-丙氨酸，细菌细胞壁形成的主要组成部分，培养基抑制了大肠杆菌和肺炎克雷伯菌中细胞分裂所需的ftsZ基因的表达，从而抑制生长。即使当存在D-丙氨酸时,ftsZ的过表达也恢复了大肠杆菌的生长。我们发现D-丙氨酸不仅通过肠上皮细胞中的孔形成抑制病理性肺炎克雷伯菌对宿主的侵袭，而且还抑制大肠杆菌的生长和抗生素抗性菌株的产生。
结论：D-氨基酸通过对肠道微生物群落的影响，可能具有用于针对变形杆菌相关菌群失调和抗生素耐药性细菌疾病的新型治疗方法的潜力。
方法：分析溃疡性结肠炎（UC）患者和健康对照者的粪便和血液中D-与L-氨基酸的比例。此外，分析了UC患者的微生物组成。用D-氨基酸处理小鼠右旋糖酐硫酸钠结肠炎模型和肝胆管炎模型。
结果：UC患者粪便中D-与L-氨基酸的比例低于健康对照组。补充D-氨基酸通过抑制变形杆菌的生长改善UC相关的实验性结肠炎和肝胆管炎。添加D-丙氨酸，细菌细胞壁形成的主要组成部分，培养基抑制了大肠杆菌和肺炎克雷伯菌中细胞分裂所需的ftsZ基因的表达，从而抑制生长。即使当存在D-丙氨酸时,ftsZ的过表达也恢复了大肠杆菌的生长。我们发现D-丙氨酸不仅通过肠上皮细胞中的孔形成抑制病理性肺炎克雷伯菌对宿主的侵袭，而且还抑制大肠杆菌的生长和抗生素抗性菌株的产生。
结论：D-氨基酸通过对肠道微生物群落的影响，可能具有用于针对变形杆菌相关菌群失调和抗生素耐药性细菌疾病的新型治疗方法的潜力。
