School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, China.
Appl Microbiol Biotechnol. 2022 Sep;106(18):6181-6194. doi: 10.1007/s00253-022-12124-5. Epub 2022 Aug 13.
Probiotics have the potential to be used in the prevention of Clostridioides difficile infection (CDI). In this study, selenium (Se)-enriched Bifidobacterium breve YH68-Se was obtained under optimal culture conditions with single-factor and response surface optimization. The overall environmental resistance of YH68-Se was superior to that of the parental strain YH68, mainly reflected in the substantial improvement of antioxidant activity and gastrointestinal tolerance. YH68-Se dramatically inhibited C. difficile growth, spore, biofilm, toxin production, and virulence gene expression, rapidly disrupted C. difficile cell membrane permeability and integrity, and altered the membrane proton motive force (PMF), induced a large outflow of intracellular substances and eventually caused bacterial death. The main factor inducing this process originated from the lactic acid (LD) in YH68-Se. In addition, the LD production of YH68 increased with increasing selenite concentration and was accompanied by enhanced activities of thioredoxin reductase (TrxR), glutathione peroxidase (GSH-Px), and increased concentration of autoinducer-2 (AI-2), which may be the crucial factors contributing to the outstanding probiotic properties of YH68-Se and their potent antagonism of C. difficile. KEY POINTS: • Compared with the parental strain B. breve YH68, the environmental resistance of YH68-Se was improved. • YH68-Se was able to produce more lactic acid, which suppressed the important physiological activities of C. difficile and rapidly disrupted their cell membrane structures. • Sodium selenite in the suitable concentration range gradually increases the yield of lactic acid and phenylacetic acid, increased the concentration of autoinducer-2, and enhanced the activities of antioxidant enzymes TrxR and GSH-Px in YH68.
益生菌具有预防艰难梭菌感染(CDI)的潜力。在这项研究中,通过单因素和响应面优化,在最佳培养条件下获得了富硒短双歧杆菌 YH68-Se。YH68-Se 的整体环境抗性优于亲本菌株 YH68,主要表现在抗氧化活性和胃肠道耐受性的显著提高。YH68-Se 可显著抑制艰难梭菌的生长、孢子、生物膜、毒素产生和毒力基因表达,迅速破坏艰难梭菌细胞膜的通透性和完整性,并改变膜质子动势(PMF),导致大量细胞内物质外流,最终导致细菌死亡。引起这一过程的主要因素来源于 YH68-Se 中的乳酸(LD)。此外,随着亚硒酸钠浓度的增加,YH68 的 LD 产量增加,同时硫氧还蛋白还原酶(TrxR)、谷胱甘肽过氧化物酶(GSH-Px)的活性增强,内源性诱导物-2(AI-2)的浓度增加,这可能是 YH68-Se 表现出优异的益生菌特性及其对艰难梭菌的有效拮抗作用的关键因素。关键点:
与亲本菌株短双歧杆菌 YH68 相比,YH68-Se 的环境抗性得到了提高。
YH68-Se 能够产生更多的乳酸,抑制艰难梭菌的重要生理活性,并迅速破坏其细胞膜结构。
适宜浓度范围内的亚硒酸钠逐渐增加乳酸和苯乙酸的产量,增加内源性诱导物-2 的浓度,增强抗氧化酶 TrxR 和 GSH-Px 在 YH68 中的活性。