State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, 130062, China.
Institute of Special Animal and Plant Sciences of Chinese Academy of Agricultural Sciences, Changchun, 130112, Jilin, China.
J Transl Med. 2024 Mar 25;22(1):308. doi: 10.1186/s12967-024-05026-9.
Ulcerative colitisis (UC) classified as a form of inflammatory bowel diseases (IBD) characterized by chronic, nonspecific, and recurrent symptoms with a poor prognosis. Common clinical manifestations of UC include diarrhea, fecal bleeding, and abdominal pain. Even though anti-inflammatory drugs can help alleviate symptoms of IBD, their long-term use is limited due to potential side effects. Therefore, alternative approaches for the treatment and prevention of inflammation in UC are crucial.
This study investigated the synergistic mechanism of Lactobacillus plantarum SC-5 (SC-5) and tyrosol (TY) combination (TS) in murine colitis, specifically exploring their regulatory activity on the dextran sulfate sodium (DSS)-induced inflammatory pathways (NF-κB and MAPK) and key molecular targets (tight junction protein). The effectiveness of 1 week of treatment with SC-5, TY, or TS was evaluated in a DSS-induced colitis mice model by assessing colitis morbidity and colonic mucosal injury (n = 9). To validate these findings, fecal microbiota transplantation (FMT) was performed by inoculating DSS-treated mice with the microbiota of TS-administered mice (n = 9).
The results demonstrated that all three treatments effectively reduced colitis morbidity and protected against DSS-induced UC. The combination treatment, TS, exhibited inhibitory effects on the DSS-induced activation of mitogen-activated protein kinase (MAPK) and negatively regulated NF-κB. Furthermore, TS maintained the integrity of the tight junction (TJ) structure by regulating the expression of zona-occludin-1 (ZO-1), Occludin, and Claudin-3 (p < 0.05). Analysis of the intestinal microbiota revealed significant differences, including a decrease in Proteus and an increase in Lactobacillus, Bifidobacterium, and Akkermansia, which supported the protective effect of TS (p < 0.05). An increase in the number of Aspergillus bacteria can cause inflammation in the intestines and lead to the formation of ulcers. Bifidobacterium and Lactobacillus can regulate the micro-ecological balance of the intestinal tract, replenish normal physiological bacteria and inhibit harmful intestinal bacteria, which can alleviate the symptoms of UC. The relative abundance of Akkermansia has been shown to be negatively associated with IBD. The FMT group exhibited alleviated colitis, excellent anti-inflammatory effects, improved colonic barrier integrity, and enrichment of bacteria such as Akkermansia (p < 0.05). These results further supported the gut microbiota-dependent mechanism of TS in ameliorating colonic inflammation.
In conclusion, the TS demonstrated a remission of colitis and amelioration of colonic inflammation in a gut microbiota-dependent manner. The findings suggest that TS could be a potential natural medicine for the protection of UC health. The above results suggest that TS can be used as a potential therapeutic agent for the clinical regulation of UC.
溃疡性结肠炎(UC)被归类为炎症性肠病(IBD)的一种形式,其特征为慢性、非特异性和反复发作,预后较差。UC 的常见临床表现包括腹泻、粪便出血和腹痛。尽管抗炎药可以帮助缓解 IBD 的症状,但由于潜在的副作用,其长期使用受到限制。因此,治疗和预防 UC 炎症的替代方法至关重要。
本研究探讨了植物乳杆菌 SC-5(SC-5)和酪醇(TY)联合(TS)在鼠结肠炎中的协同作用机制,特别研究了它们对葡聚糖硫酸钠(DSS)诱导的炎症途径(NF-κB 和 MAPK)和关键分子靶标(紧密连接蛋白)的调节作用。通过评估 DSS 诱导的结肠炎小鼠模型中结肠炎发病率和结肠黏膜损伤(n=9),评估 SC-5、TY 或 TS 治疗 1 周的效果。为了验证这些发现,通过将接受 TS 处理的小鼠的微生物群接种到接受 DSS 处理的小鼠中,进行粪便微生物群移植(FMT)(n=9)。
结果表明,所有三种治疗方法均能有效降低结肠炎发病率并预防 DSS 诱导的 UC。联合治疗 TS 对 DSS 诱导的丝裂原激活蛋白激酶(MAPK)的激活具有抑制作用,并负调控 NF-κB。此外,TS 通过调节 zona-occludin-1(ZO-1)、Occludin 和 Claudin-3 的表达来维持紧密连接(TJ)结构的完整性(p<0.05)。肠道微生物组的分析显示出显著差异,包括变形菌属数量减少和乳杆菌属、双歧杆菌属和阿克曼菌属数量增加,这支持了 TS 的保护作用(p<0.05)。曲霉菌属数量的增加会导致肠道炎症,并导致溃疡形成。双歧杆菌属和乳杆菌属可以调节肠道微生态平衡,补充正常生理细菌并抑制有害肠道细菌,从而缓解 UC 症状。阿克曼菌属的相对丰度与 IBD 呈负相关。FMT 组表现出减轻的结肠炎、出色的抗炎作用、改善的结肠屏障完整性以及阿克曼菌属等细菌的富集(p<0.05)。这些结果进一步支持了 TS 通过肠道微生物群依赖性机制改善结肠炎症的作用。
总之,TS 以肠道微生物群依赖性的方式表现出对结肠炎的缓解和对结肠炎症的改善。研究结果表明,TS 可能是一种保护 UC 健康的潜在天然药物。上述结果表明,TS 可作为临床调节 UC 的潜在治疗剂。