Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824, USA.
Food Funct. 2021 Jun 21;12(12):5591-5606. doi: 10.1039/d1fo00166c.
Colitis caused by non-typhoidal Salmonella (NST) infection is increasingly serious and widespread, so new effective treatment strategies with little or no side-effects are urgently needed. Our previous research found that phenyl lactic acid (PLA) derived from Lactobacillus plantarum ZJ316 can effectively inhibit Salmonella enterica Typhimurium (S. Typhimurium). In this study, we further investigated the protective effects of this PLA against S. Typhimurium-induced colitis in mice. An infection model was established using female C57BL/6J mice by oral administration of 109 CFU mL-1 of S. Typhimurium, and PLA was supplied for 10 days after infection. In colitic mice, PLA administration reduced the disease activity index, prevented the colon shortening and spleen enlargement, decreased liver enzyme (AST and ALT) activities, and alleviated the colonic tissue damage. RT-qPCR analysis showed that PLA significantly down-regulated the levels of NF-κB, TLR4 and pro-inflammatory cytokines (IFN-γ, IL-1β and TNF-α), but stimulated the mRNA expression of the anti-inflammatory cytokine IL-10. Changes in intestinal microecology were analyzed by 16S rRNA sequencing. PLA modulated colonic microbiota dysbiosis by increasing the abundance of Lactobacillus, Butyricicoccus and Roseburia, and reducing Salmonella and Alloprevotella at the genus level. In addition, PLA significantly increased the concentrations of short-chain fatty acids (SCFAs) in the colon, especially propionic acid and butyric acid. These findings revealed that PLA has potential benefits on alleviating S. Typhimurium-induced colitis mainly through intestinal microbiota regulation and inflammation elimination, providing a new perspective for the NTS infection treatment strategy.
非伤寒沙门氏菌（NTS）感染引起的结肠炎越来越严重且广泛，因此迫切需要新的有效治疗策略，且副作用小或无副作用。我们之前的研究发现，植物乳杆菌 ZJ316 衍生的苯乳酸（PLA）可有效抑制肠炎沙门氏菌（S. Typhimurium）。在这项研究中，我们进一步研究了 PLA 对 S. Typhimurium 诱导的结肠炎小鼠的保护作用。通过口服给予 109 CFU mL-1 的 S. Typhimurium 建立感染模型，在感染后 PLA 给药 10 天。在结肠炎小鼠中，PLA 给药降低了疾病活动指数，防止了结肠缩短和脾脏肿大，降低了肝酶（AST 和 ALT）活性，并缓解了结肠组织损伤。RT-qPCR 分析显示，PLA 显著下调 NF-κB、TLR4 和促炎细胞因子（IFN-γ、IL-1β 和 TNF-α）的水平，但刺激抗炎细胞因子 IL-10 的 mRNA 表达。通过 16S rRNA 测序分析肠道微生物组变化。PLA 通过增加乳杆菌、丁酸梭菌和罗斯伯里氏菌的丰度，降低属水平的沙门氏菌和 Alloprevotella，调节结肠微生物群失调。此外，PLA 显著增加了结肠中短链脂肪酸（SCFAs）的浓度，特别是丙酸和丁酸。这些发现表明，PLA 通过调节肠道微生物群和消除炎症，对缓解 S. Typhimurium 诱导的结肠炎具有潜在益处，为 NTS 感染治疗策略提供了新视角。
