Pang Bing, Jin Han, Liao Ning, Li Junjun, Jiang Chunmei, Shao Dongyan, Shi Junling
Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 Youyi West Road, Xi'an, Shaanxi Province 710072, China.
Food Funct. 2021 Jun 8;12(11):5171-5186. doi: 10.1039/d0fo03479g.
Gut microbiota imbalance is one of the major causes of ulcerative colitis (UC). L. rhamnosus SHA113 (LRS), a strain isolated from healthy human milk, influences the regulation of gut flora. This study aims to determine whether this strain can ameliorate UC by modulating gut microbiota. Mouse models of UC were established using C57BL/6Cnc mice with intragastric administration of 3.0% (w/v) dextran sodium sulfate (DSS). LRS was used to treat the mouse models of UC with 109 cfu mL-1 cell suspension via intragastric administration. To verify the effect of gut microbiota on UC, fecal microbiota collected from the mice after the treatment with LRS were also used to treat the UC mouse models (FMT). The severity of UC was evaluated based on body weight, colon length, disease activity index (DAI), and hematoxylin-eosin staining. The microbial composition was analyzed by 16S rRNA sequencing. The mRNA expression levels of cytokines, mucins, tight junction proteins, and antimicrobial peptides in the gastrointestinal tract were detected by quantitative real-time polymerase chain reaction. The short-chain fatty acid (SCFAs) in the cecal contents of all mice were quantitatively detected by gas chromatography and mass spectrometry. Both LRS and FMT exerted excellent therapeutic effects on UC, as evidenced by the reduction in body weight loss, colon length, and colon structural integrity, as well as the increase in the DAI (disease activity index). LRS and FMT treatments showed similar effects: (1) an increase of total SCFA production in the cecal contents and the abundance of gut microbial diversity and flora composition; (2) decreases in two genera (Parabacteroides and Escherichia/Shigella) related to the DAI and the enhancement of SCFAs and IL-10 positively related genera in the gut microbiota (Bilophila, Roseburia, Akkermansia, and Bifidobacterium); (3) downregulation of the expression of tumor necrosis factor-α, interleukin IL-6, and IL-1β, and upregulation of the expression of the anti-inflammatory cytokine IL-10; and (4) upregulation of the expression of mucins (Muc1-4) and tight junction protein ZO-1. Overall, L. rhamnosus SHA113 relieves UC via the regulation of gut microbiota: increases in SCFA-producing genera and decreases in UC-related genera. In addition, a single strain is sufficient to induce a significant change in the gut microbiota and exert therapeutic effects on UC.
肠道微生物群失衡是溃疡性结肠炎（UC）的主要病因之一。从健康人乳中分离出的鼠李糖乳杆菌SHA113（LRS）会影响肠道菌群的调节。本研究旨在确定该菌株是否能通过调节肠道微生物群来改善UC。通过对C57BL/6Cnc小鼠进行胃内给予3.0%（w/v）葡聚糖硫酸钠（DSS）来建立UC小鼠模型。使用浓度为109 cfu mL-1的细胞悬液通过胃内给药的方式用LRS治疗UC小鼠模型。为了验证肠道微生物群对UC的影响，还使用从LRS治疗后的小鼠收集的粪便微生物群来治疗UC小鼠模型（粪菌移植，FMT）。基于体重、结肠长度、疾病活动指数（DAI）和苏木精-伊红染色来评估UC的严重程度。通过16S rRNA测序分析微生物组成。通过定量实时聚合酶链反应检测胃肠道中细胞因子、粘蛋白、紧密连接蛋白和抗菌肽的mRNA表达水平。通过气相色谱和质谱法定量检测所有小鼠盲肠内容物中的短链脂肪酸（SCFA）。LRS和FMT对UC均具有出色的治疗效果，体重减轻、结肠长度和结肠结构完整性的降低以及DAI（疾病活动指数）的增加都证明了这一点。LRS和FMT治疗显示出相似的效果：（1）盲肠内容物中总SCFA产量增加，肠道微生物多样性和菌群组成的丰度增加；（2）与DAI相关的两个属（副拟杆菌属和埃希氏菌属/志贺氏菌属）减少，以及肠道微生物群中与SCFAs和IL-10呈正相关的属（嗜胆菌属、罗斯氏菌属、阿克曼氏菌属和双歧杆菌属）增加；（3）肿瘤坏死因子-α、白细胞介素IL-6和IL-1β的表达下调，以及抗炎细胞因子IL-10的表达上调；（4）粘蛋白（Muc1-4）和紧密连接蛋白ZO-1的表达上调。总体而言，鼠李糖乳杆菌SHA113通过调节肠道微生物群来缓解UC：增加产生SCFA的属并减少与UC相关的属。此外，单一菌株足以引起肠道微生物群的显著变化并对UC发挥治疗作用。
