Hu Xiangdong, Han Xuebing, Liu Gang, Guan Guiping, Xia Chenmei
Department of Gastroenterology, The First People's Hospital of Wenling, Wenling, China.
Hunan Provincial Engineering Research Center of Applied Microbial Resources Development for Livestock and Poultry, College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, China.
Front Microbiol. 2025 Jul 22;16:1597774. doi: 10.3389/fmicb.2025.1597774. eCollection 2025.
Intestinal homeostasis depends critically on the dynamic interplay between gut microbiota, epithelial barriers, and host immunity, dysregulation of this triad can initiate inflammatory cascades. Ferulic acid and its derivative N-Feruloylserotonin demonstrate significant anti-inflammatory activity, though their intestinal protective effects and mechanisms require further elucidation. Therefore, this study examined how these compounds mitigate lipopolysaccharide (LPS)-induced acute inflammation through integrated modulation of the gut microbiome, serum metabolome, and transcriptional networks. Our findings reveal that both compounds, attenuated LPS-induced intestinal pathology in murine models, suppressed pro-inflammatory cytokine expression, elevated beneficial metabolites including 1-naphthalenesulfonic acid, enriched probiotic taxa (Ruminococcaceae, Muribaculaceae, Lachnospiraceae, Bifidobacteriaceae, Prevotellaceae, Roseburia, Blautia, and Butyricicoccus), and suppressed pathobionts (Proteobacteria, Gammaproteobacteria, Enterobacterales, and Bacillus). Transcriptomic profiling further implicated modulation of antigen processing and presentation, NF-κB signal pathway, MAPK signal pathway, and PI3K-Akt signal pathway. Key regulatory targets identified include: Pik3cd, H2-DMb1, H2-Oa, Kdr, Fgfr3, Il1r2, Rac, Irak4, Traf6, Ticam1, Rip1, and Rip3. This work establishes a mechanistic foundation for deploying ferulic acid and N-Feruloylserotonin in intestinal health preservation and inflammatory disease prevention, while providing novel insights into microbiota-homeostasis crosstalk.
肠道稳态关键取决于肠道微生物群、上皮屏障和宿主免疫之间的动态相互作用，这三者的失调会引发炎症级联反应。阿魏酸及其衍生物N-阿魏酰血清素具有显著的抗炎活性，但其肠道保护作用及机制仍需进一步阐明。因此，本研究探讨了这些化合物如何通过对肠道微生物组、血清代谢组和转录网络的综合调节来减轻脂多糖（LPS）诱导的急性炎症。我们的研究结果表明，这两种化合物均可减轻小鼠模型中LPS诱导的肠道病理变化，抑制促炎细胞因子表达，提高有益代谢产物（包括1-萘磺酸）水平，富集益生菌类群（瘤胃球菌科、毛螺菌科、螺旋体科、双歧杆菌科、普雷沃氏菌科、罗斯氏菌属、布劳特氏菌属和丁酸球菌属），并抑制致病共生菌（变形菌门、γ-变形菌纲、肠杆菌目和芽孢杆菌属）。转录组分析进一步表明其对抗抗原加工和呈递、NF-κB信号通路、MAPK信号通路和PI3K-Akt信号通路的调节作用。确定的关键调控靶点包括：Pik3cd、H2-DMb1、H2-Oa、Kdr、Fgfr3、Il1r2、Rac、Irak4、Traf6、Ticam1、Rip1和Rip3。这项工作为在肠道健康维护和炎症性疾病预防中应用阿魏酸和N-阿魏酰血清素奠定了机制基础，同时为微生物群-稳态相互作用提供了新的见解。
