炎症相关结直肠癌癌症中的肠道微生物代谢产物：机制和治疗意义
Gut microbial metabolites in inflammation-associated colorectal cancer: mechanisms and therapeutic implications.
摘要(中文译文)
结肠炎相关结直肠癌（CAC）是炎症性肠病（IBD）最严重的恶性并发症，以高侵袭性、频繁复发和预后不良为特征。近年研究表明，肠道微生物代谢物通过“代谢物—信号通路—表观遗传”调控网络参与CAC的发生与进展，呈现出显著的双重调控作用。保护性代谢物，如短链脂肪酸（SCFAs）、色氨酸衍生物（如吲哚类化合物）和维生素B2，发挥抗炎、抗氧化、增强肠道屏障及抑制致癌通路的作用。相反，致病性代谢物促进癌变。此类代谢物中较为突出的包括次级胆汁酸[如脱氧胆酸（DCA）]、氧化三甲胺（TMAO）和高浓度硫化氢（H₂S）。这些代谢物激活核因子κB（NF-κB），刺激促炎细胞因子释放，诱导DNA损伤，并破坏免疫稳态。反之，血浆TMAO水平升高与不良生存结局密切相关，高危个体的全因死亡和复发风险显著增加。本综述系统总结了多种关键肠道菌群来源代谢物的微生物来源、在CAC中的双重机制及潜在治疗价值，包括SCFAs、琥珀酸、次级胆汁酸、TMAO、色氨酸代谢物、多胺、H₂S和维生素B2。基于现有证据，干预策略主要集中于通过益生菌/益生元调节微生物代谢平衡，通过膳食纤维补充增加有益代谢物的前体供给，通过菌群移植重建肠道稳态，以及开发代谢物类似物或螯合剂进行靶向干预。尽管肠道微生物代谢物为CAC的早期诊断生物标志物和靶向治疗提供了新范式，但临床转化仍面临诸多挑战，包括个体间微生物异质性、代谢物与疾病之间因果关系的建立以及临床干预途径的优化，这些均有待进一步研究突破。
Abstract
Colitis-associated colorectal cancer (CAC) represents the most severe malignant complication of inflammatory bowel disease (IBD), characterized by high invasiveness, frequent recurrence, and poor prognosis. Recent studies have revealed that gut microbial metabolites are involved in the initiation and progression of CAC through a "metabolite-signaling pathway-epigenetics" regulatory network, demonstrating a remarkable dual modulatory role. Protective metabolites, such as short-chain fatty acids (SCFAs), tryptophan derivatives (e.g., indole compounds), and vitamin B2, exert anti-inflammatory, antioxidant, intestinal barrier-enhancing, and oncogenic pathway-suppressing effects. In contrast, pathogenic metabolites promote carcinogenesis. Prominent among such metabolites are secondary bile acids [e.g., deoxycholic acid (DCA)], trimethylamine N-oxide (TMAO), and high concentrations of hydrogen sulfide (HS). These metabolites activate nuclear factor κB (NF-κB), stimulate the release of pro-inflammatory cytokines, induce DNA damage, and disrupt immune homeostasis. Conversely, elevated plasma TMAO levels are closely associated with poor survival outcomes, with high-risk individuals showing significantly increased risks of all-cause mortality and recurrence. This review systematically summarizes the microbial origins, dual mechanisms in CAC, and potential therapeutic value of several key gut microbiota-derived metabolites, including SCFAs, succinate, secondary bile acids, TMAO, tryptophan metabolites, polyamines, HS, and vitamin B2. Based on current evidence, intervention strategies are primarily focused on regulating microbial metabolic balance via probiotics/prebiotics, increasing precursor supply of beneficial metabolites through dietary fiber supplementation, reconstructing gut homeostasis via microbiota transplantation, and developing metabolite analogs or chelators for targeted intervention. Although gut microbial metabolites offer new paradigms for early diagnostic biomarkers and targeted therapies in CAC, clinical translation still faces several challenges, including interindividual microbial heterogeneity, establishment of causal relationships between metabolites and disease, and optimization of clinical intervention pathways, which require further research breakthroughs.
如何引用
AMA
Yafang Li, Qinglong Wu, Jing Zhang, Qingqing Xun. Gut microbial metabolites in inflammation-associated colorectal cancer: mechanisms and therapeutic implications.. Frontiers in microbiology. 2026; doi:10.3389/fmicb.2026.1802686.
APA
Yafang Li, Qinglong Wu, Jing Zhang, Qingqing Xun (2026). Gut microbial metabolites in inflammation-associated colorectal cancer: mechanisms and therapeutic implications.. Frontiers in microbiology. https://doi.org/10.3389/fmicb.2026.1802686
GB/T 7714
Yafang Li, Qinglong Wu, Jing Zhang, Qingqing Xun. Gut microbial metabolites in inflammation-associated colorectal cancer: mechanisms and therapeutic implications.[J]. Frontiers in microbiology, 2026 doi:10.3389/fmicb.2026.1802686.
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