School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, Heilongjiang, China.
Dairy Nutrition and Function, Key Laboratory of Sichuan Province, New Hope Dairy Company Limited, Chengdu 610023, China; Sichuan Engineering Laboratory for High-quality Dairy Product Preparation and Quality Control Technology, Chengdu 610000, Sichuan, China; Chengdu Molecular Power Biotechnology Co., Ltd., Chengdu 611732, Sichuan, China.
Food Res Int. 2024 Dec;197(Pt 1):115164. doi: 10.1016/j.foodres.2024.115164. Epub 2024 Oct 9.
The prevalence and severity of gastrointestinal diseases were increased with age. In this study, the intestinal protective effects of Lactococcus lactis HF08 (HF08) and its derived postbiotic (P-HF08) on D-gal-induced aging mice and D-gal/DSS-induced aging colitis mice were investigated. In D-gal-induced aging mice, both HF08 and P-HF08 alleviated aging-related intestinal barrier dysfunction, inflammatory status, and gut microbiota disorder. The effects of probiotic HF08 were superior to those of postbiotic P-HF08, attributed to ability of HF08 to regulate the gut microbiota. However, in D-gal/DSS-induced aging colitis mice, the effects of P-HF08 on colitis surpassed that of HF08. Specifically, both HF08 and P-HF08 could reduce symptoms of age-related colitis, including reduction of lose weight, the DAI score, colonic shortening, and colon tissue damage. The inhibitory effects of P-HF08 on intestinal inflammation surpassed those of HF08, as evidenced by the levels of colon IL-6, IL-1β, and IL-10. Western blot results demonstrated that the anti-inflammatory effects of P-HF08 were attributed to the downregulation of key proteins in the TLR4/NF-κB pathway. And four potential TLR4 inhibitors were identified from HF08 metabolites (eplerenone, genistein, indoleacrylic acid, and turanose) by molecular docking. Nevertheless, HF08 could better regulate gut microbiota and metabolite in aging-related colitis than P-HF08, which was consistent with the results on aging mice. Overall, our finding revealed that when the intestinal barrier was intact (aging), probiotics showed superior regulation of intestinal microbiota, while postbiotics offered greater safety in case of intestinal barrier damage (aging colitis). This study offered a novel perspective into the applications of probiotics and their derivatives in the aging related gastrointestinal diseases adjuvant therapy.
胃肠道疾病的患病率和严重程度随年龄增长而增加。本研究旨在探讨乳球菌乳亚种 HF08（HF08）及其衍生后生元（P-HF08）对 D-半乳糖诱导的衰老小鼠和 D-半乳糖/葡聚糖硫酸钠（DSS）诱导的衰老结肠炎小鼠的肠道保护作用。在 D-半乳糖诱导的衰老小鼠中，HF08 和 P-HF08 均能缓解衰老相关的肠道屏障功能障碍、炎症状态和肠道微生物群紊乱。益生菌 HF08 的作用优于后生元 P-HF08，这归因于 HF08 调节肠道微生物群的能力。然而，在 D-半乳糖/DSS 诱导的衰老结肠炎小鼠中，P-HF08 对结肠炎的作用优于 HF08。具体而言，HF08 和 P-HF08 均可减轻与年龄相关的结肠炎症状，包括减轻体重减轻、DAI 评分、结肠缩短和结肠组织损伤。P-HF08 对肠道炎症的抑制作用优于 HF08，表现在结肠 IL-6、IL-1β 和 IL-10 水平降低。Western blot 结果表明，P-HF08 的抗炎作用归因于 TLR4/NF-κB 通路关键蛋白的下调。通过分子对接从 HF08 代谢物（依普利酮、染料木黄酮、吲哚丙烯酸和松三糖）中鉴定出四种潜在的 TLR4 抑制剂。然而，HF08 在衰老相关结肠炎中比 P-HF08 更好地调节肠道微生物群和代谢物，这与衰老小鼠的结果一致。总的来说，本研究结果表明，当肠道屏障完整时（衰老），益生菌对肠道微生物群的调节作用更好，而后生元在肠道屏障受损时（衰老结肠炎）具有更大的安全性。本研究为益生菌及其衍生物在衰老相关胃肠道疾病辅助治疗中的应用提供了新的视角。
