基于色氨酸代谢的溃疡性结肠炎相关研究进展

doi:10.3877/cma.j.issn.1674-1358.2025.06.001

溃疡性结肠炎（UC）是一种慢性炎症性肠道疾病，发病部位主要局限于结直肠的黏膜和黏膜下层，多表现为腹泻、黏液脓血便、腹痛，发作与缓解交替，其发病机制尚不明确，与环境、遗传、肠道微生物以及免疫等多种因素有关。色氨酸作为人体的必需氨基酸，其分解代谢主要通过犬尿氨酸、吲哚和5-羟色胺3条途径进行。色氨酸的多种代谢产物可调节肠道屏障功能、免疫应答、炎症反应以及肠道菌群等，进而影响UC疾病进程。探索色氨酸代谢紊乱与UC的相关性，有望开发UC新型辅助治疗方法。本文对色氨酸代谢的3条途径、色氨酸代谢紊乱与UC的病理机制、基于色氨酸代谢的UC治疗策略相关进展进行综述。

关键词: 色氨酸, 溃疡性结肠炎, 代谢, 治疗

Ulcerative colitis (UC) is a chronic inflammatory bowel disease primarily localized to the mucosa and submucosa of the colorectal region. It is clinically characterized by diarrhea, bloody mucopurulent stools, abdominal pain, alternating periods of flare-ups and remission. Although its pathogenesis remains incompletely understood, it is associated with multiple factors including environment, genetics, gut microbiota and immunity. Tryptophan, an essential amino acid in humans, undergoes catabolism via three major pathways: the kynurenine, indole and 5-hydroxytryptamine pathways. Diverse tryptophan metabolites modulate intestinal barrier integrity, immune responses, inflammatory processes and microbial homeostasis, thereby influencing UC progression. Investigating the interplay between tryptophan metabolic disturbances and UC may facilitate the development of novel adjuvant therapeutic strategies. This article reviews the research progress on the three pathways of tryptophan metabolism, the pathological mechanisms linking tryptophan metabolism disorders to UC, and the UC treatment strategies targeting tryptophan metabolism.

Key words: Tryptophan, Ulcerative colitis, Metabolism, Treatment

表1 色氨酸代谢产物及其在UC中的生物学作用与机制

代谢途径	代谢物	涉及受体或通路	作用	参考文献
KP	KYN	AhR	调节免疫反应	^[20-21]
	KYNA	AhR	改善肠道屏障功能、调节细胞能量代谢	^[22]
	XANA	AhR	改善肠道屏障功能、调节细胞能量代谢	^[22]
吲哚途径	ILA	AhR、Nrf2信号通路、NF-κB信号通路、HIF信号通路	改善肠道屏障功能、抗炎、调节免疫反应	^[23-24]
	IAA	AhR、ERK信号通路	改善肠道屏障功能、抗炎	^[25,26,27]
	IPA	AhR	改善肠道菌群失调、抗炎、调节免疫反应	^[28]
	I3Ald	AhR	改善肠道屏障功能	^[27]
	I3A	AhR、TLR4、NF-κB信号通路、p38 MAPK信号通路	改善肠道屏障功能、抗炎、平衡氨基酸代谢	^[29-30]
	I3E	AhR	改善肠道屏障功能	^[31]
	I3P	AhR	改善肠道屏障功能	^[31]
5-HT途径	5-HT	5-HT₃R	促炎、增强肠道蠕动和分泌	^[32-33]
		5-HT₄R	促炎、改善肠道屏障功能	^{[32, 34]}
		5-HT₇R	促炎	^[32]

表1 色氨酸代谢产物及其在UC中的生物学作用与机制

代谢途径	代谢物	涉及受体或通路	作用	参考文献
KP	KYN	AhR	调节免疫反应	^[20-21]
	KYNA	AhR	改善肠道屏障功能、调节细胞能量代谢	^[22]
	XANA	AhR	改善肠道屏障功能、调节细胞能量代谢	^[22]
吲哚途径	ILA	AhR、Nrf2信号通路、NF-κB信号通路、HIF信号通路	改善肠道屏障功能、抗炎、调节免疫反应	^[23-24]
	IAA	AhR、ERK信号通路	改善肠道屏障功能、抗炎	^[25,26,27]
	IPA	AhR	改善肠道菌群失调、抗炎、调节免疫反应	^[28]
	I3Ald	AhR	改善肠道屏障功能	^[27]
	I3A	AhR、TLR4、NF-κB信号通路、p38 MAPK信号通路	改善肠道屏障功能、抗炎、平衡氨基酸代谢	^[29-30]
	I3E	AhR	改善肠道屏障功能	^[31]
	I3P	AhR	改善肠道屏障功能	^[31]
5-HT途径	5-HT	5-HT₃R	促炎、增强肠道蠕动和分泌	^[32-33]
		5-HT₄R	促炎、改善肠道屏障功能	^{[32, 34]}
		5-HT₇R	促炎	^[32]

[1]	Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies[J]. Lancet,2017,390(10114):2769-2778.
[2]	Kaplan GG. The global burden of IBD: from 2015 to 2025[J]. Nat Rev Gastroenterol Hepatol,2015,12(12):720-727.
[3]	Voelker R. What is ulcerative colitis?[J]. JAMA,2024,331(8):716.
[4]	Le Berre C, Honap S, Peyrin-Biroulet L. Ulcerative colitis[J]. Lancet,2023,402(10401):571-584.
[5]	屈霄, 王靓, 陆萍, 等. 外周血炎症因子及肠道菌群特征与活动性溃疡性结肠炎患者病情的相关性分析[J/OL]. 中华消化病与影像杂志(电子版),2023,13(6):466-470.
[6]	郭伟仪, 林沛玲. 不同抗体型幽门螺杆菌感染与溃疡性结肠炎患者疾病活动及组织学评分的关系[J/CD]. 中华实验和临床感染病杂志(电子版),2024,18(4):237-244.
[7]	Rubin DT, Allegretti JR, Panés J, et al. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies[J]. Lancet,2025,405(10472):33-49.
[8]	Sun S, Hu F, Sang Y, et al. Dysregulated tryptophan metabolism contributes to metabolic syndrome in Chinese community-dwelling older adults[J]. BMC Endo Dis,2025,25(1):7.
[9]	Jenkins TA, Nguyen JC, Polglaze KE, et al. Influence of tryptophan and serotonin on mood and cognition with a possible role of the gut-brain axis[J]. Nutrients,2016,8(1):56.
[10]	Badawy AA. Kynurenine pathway of tryptophan metabolism: regulatory and functional aspects[J]. Int J Tryptophan Res,2017,10:1178646917691938.
[11]	Deng Y, Zhou M, Wang J, et al. Involvement of the microbiota-gut-brain axis in chronic restraint stress: disturbances of the kynurenine metabolic pathway in both the gut and brain[J]. Gut Microbes,2021,13(1):1-16.
[12]	Xue C, Li G, Zheng Q, et al. Tryptophan metabolism in health and disease[J]. Cell Metab,2023,35(8):1304-1326.
[13]	Zinger A, Barcia C, Herrero MT, et al. The involvement of neuroinflammation and kynurenine pathway in Parkinson’s disease[J]. Parkinsons Dis,2011,2011:716859.
[14]	Sinclair LV, Neyens D, Ramsay G, et al. Single cell analysis of kynurenine and System L amino acid transport in T cells[J]. Nat Commun,2018,9(1):1981.
[15]	Baumgartner R, Berg M, Matic L, et al. Evidence that a deviation in the kynurenine pathway aggravates atherosclerotic disease in humans[J]. J Intern Med,2021,289(1):53-68.
[16]	Castellano-Gonzalez G, Jacobs KR, Don E, et al. Kynurenine 3-monooxygenase activity in human primary neurons and effect on cellular bioenergetics identifies new neurotoxic mechanisms[J]. Neurotox Res,2019,35(3):530-541.
[17]	Shajib MS, Chauhan U, Adeeb S, et al. Characterization of serotonin signaling components in patients with inflammatory bowel disease[J]. J Can Assoc Gastroenterol,2019,2(3):132-140.
[18]	Gershon MD. Review article: serotonin receptors and transporters--roles in normal and abnormal gastrointestinal motility[J]. Aliment Pharmacol Ther,2004,20(Suppl 7):3-14.
[19]	Hannon J, Hoyer D. Molecular biology of 5-HT receptors[J]. Behav Brain Res,2008,195(1):198-213.
[20]	Baricza E, Tamási V, Marton N, et al. The emerging role of aryl hydrocarbon receptor in the activation and differentiation of Th17 cells[J]. Cell Mol Life Sci,2016,73(1):95-117.
[21]	Lv WJ, Ma YM, Huang JY, et al. Polysaccharides derived from Shenling Baizhu San improve colitis via modulating tryptophan metabolism in mice[J]. Int J Biol Macromol,2022,222(Pt A):1127-1136.
[22]	Michaudel C, Danne C, Agus A, et al. Rewiring the altered tryptophan metabolism as a novel therapeutic strategy in inflammatory bowel diseases[J]. Gut,2023,72(7):1296-1307.
[23]	Wang A, Guan C, Wang T, et al. Lactiplantibacillus plantarum-derived indole-3-lactic acid ameliorates intestinal barrier integrity through the AhR/Nrf2/NF-κB Axis[J]. J Agric Food Chem,2024,72(16):9236-9246.
[24]	Yu K, Li Q, Sun X, et al. Bacterial indole-3-lactic acid affects epithelium-macrophage crosstalk to regulate intestinal homeostasis[J]. Proc Natl Acad Sci USA,2023,120(45):e2309032120.
[25]	Qu X, Song Y, Li Q, et al. Indole-3-acetic acid ameliorates dextran sulfate sodium-induced colitis via the ERK signaling pathway[J]. Arch Pharm Res,2024,47(3):288-299.
[26]	Li M, Ding Y, Wei J, et al. Gut microbiota metabolite indole-3-acetic acid maintains intestinal epithelial homeostasis through mucin sulfation[J]. Gut Microbes,2024,16(1):2377576.
[27]	Yang W, Ren D, Shao H, et al. Theabrownin from Fu Brick Tea improves ulcerative colitis by shaping the gut microbiota and modulating the tryptophan metabolism[J]. J Agric Food Chem,2023,71(6):2898-2913.
[28]	Fu Y, Gao H, Hou X, et al. Pretreatment with IPA ameliorates colitis in mice: Colon transcriptome and fecal 16S amplicon profiling[J]. Front Immunol,2022,13:1014881.
[29]	Ma M, Wang Y, Fan S, et al. Urolithin A alleviates colitis in mice by improving gut microbiota dysbiosis, modulating microbial tryptophan metabolism, and triggering AhR activation[J]. J Agric Food Chem,2023,71(20):7710-7722.
[30]	Liu M, Wang Y, Xiang H, et al. The tryptophan metabolite indole-3-carboxaldehyde alleviates mice with DSS-induced ulcerative colitis by balancing amino acid metabolism, inhibiting intestinal inflammation, and improving intestinal barrier function[J]. Molecules,2023,28(9):3704.
[31]	Scott SA, Fu J, Chang PV. Microbial tryptophan metabolites regulate gut barrier function via the aryl hydrocarbon receptor[J]. Proc Natl Acad Sci USA,2020,117(32):19376-19387.
[32]	Dürk T, Panther E, Müller T, et al. 5-Hydroxytryptamine modulates cytokine and chemokine production in LPS-primed human monocytes via stimulation of different 5-HTR subtypes[J]. Int Immunol,2005,17(5):599-606.
[33]	Maehara T, Matsumoto K, Horiguchi K, et al. Therapeutic action of 5-HT3 receptor antagonists targeting peritoneal macrophages in post-operative ileus[J]. Br J Pharmacol,2015,172(4):1136-1147.
[34]	Bhattarai Y, Jie S, Linden DR, et al. Bacterially derived tryptamine increases mucus release by activating a host receptor in a mouse model of inflammatory bowel disease[J]. iScience,2020,23(12):101798.
[35]	Metz R, Duhadaway JB, Kamasani U, et al. Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2, 3-dioxygenase inhibitory compound D-1-methyl-tryptophan[J]. Cancer Res,2007,67(15):7082-7087.
[36]	Zhao LP, Wu J, Quan W, et al. DSS-induced colitis activates the kynurenine pathway in serum and brain by affecting IDO-1 and gut microbiota[J]. Front Immunol,2022,13:1089200.
[37]	Yu F, Du Y, Li C, et al. Association between metabolites in tryptophan-kynurenine pathway and inflammatory bowel disease: a two-sample Mendelian randomization[J]. Sci Rep,2024,14(1):201.
[38]	Munn DH, Sharma MD, Baban B, et al. GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2, 3-dioxygenase[J]. Immunity,2005,22(5):633-642.
[39]	Joisten N, Ruas JL, Braidy N, et al. The kynurenine pathway in chronic diseases: a compensatory mechanism or a driving force?[J]. Trends Mol Med,2021,27(10):946-954.
[40]	Wnorowski A, Wnorowska S, Kurzepa J, et al. Alterations in kynurenine and NAD(+) salvage pathways during the successful treatment of inflammatory bowel disease suggest HCAR3 and NNMT as potential drug targets[J]. Int J Mol Sci,2021,22(24):13497.
[41]	Shin JH, Lee YK, Shon WJ, et al. Gut microorganisms and their metabolites modulate the severity of acute colitis in a tryptophan metabolism-dependent manner[J]. Eur J Nutr,2020,59(8):3591-3601.
[42]	Shi Y, Luo S, Zhai J, et al. A novel causative role of imbalanced kynurenine pathway in ulcerative colitis: Upregulation of KMO and KYNU promotes intestinal inflammation[J]. Biochim Biophys Acta Mol Basis Dis,2024,1870(2):166929.
[43]	Tashita C, Hoshi M, Hirata A, et al. Kynurenine plays an immunosuppressive role in 2 4, 6-trinitrobenzene sulfate-induced colitis in mice[J]. World J Gastroenterol,2020,26(9):918-932.
[44]	Mar JS, Ota N, Pokorzynski ND, et al. IL-22 alters gut microbiota composition and function to increase aryl hydrocarbon receptor activity in mice and humans[J]. Microbiome,2023,11(1):47.
[45]	Wang G, Fan Y, Zhang G, et al. Microbiota-derived indoles alleviate intestinal inflammation and modulate microbiome by microbial cross-feeding[J]. Microbiome,2024,12(1):59.
[46]	Shen J, Yang L, You K, et al. Indole-3-acetic acid alters intestinal microbiota and alleviates ankylosing spondylitis in mice[J]. Front Immunol,2022,13:762580.
[47]	Zhang X, Shi L, Wang N, et al. Gut bacterial indole-3-acetic acid induced immune promotion mediates preventive effects of Fu Brick Tea polyphenols on experimental colitis[J]. J Agric Food Chem,2023,71(2):1201-1213.
[48]	Wang Y, Ji X, Zhao M, et al. Modulation of tryptophan metabolism via AHR-IL22 pathway mediates the alleviation of DSS-induced colitis by chitooligosaccharides with different degrees of polymerization[J]. Carbohydr Polym,2023,319:121180.
[49]	Ihekweazu FD, Engevik MA, Ruan W, et al. Bacteroides ovatus promotes IL-22 production and reduces trinitrobenzene sulfonic acid-driven colonic inflammation[J]. Am J Pathol,2021,191(4):704-719.
[50]	Suga N, Murakami A, Arimitsu H, et al. Luteolin suppresses 5-hydroxytryptamine elevation in stimulated RBL-2H3 cells and experimental colitis mice[J]. J Clin Biochem Nutr,2021,69(1):20-27.
[51]	Jørandli JW, Thorsvik S, Skovdahl HK, et al. The serotonin reuptake transporter is reduced in the epithelium of active Crohn’s disease and ulcerative colitis[J]. Am J Physiol Gastrointest Liver Physiol,2020,319(6):G761-G768.
[52]	Kwon YH, Wang H, Denou E, et al. Modulation of gut microbiota composition by serotonin signaling influences intestinal immune response and susceptibility to colitis[J]. Cell Mol Gastroenterol Hepatol,2019,7(4):709-728.
[53]	Mawe GM, Hurd M, Hennig GW, et al. Epithelial 5-HT(4) receptors as a target for treating constipation and intestinal inflammation[J]. Adv Exp Med Biol,2022,1383:329-334.
[54]	Motavallian A, Minaiyan M, Rabbani M, et al. Anti-inflammatory effects of alosetron mediated through 5-HT(3) receptors on experimental colitis[J]. Res Pharm Sci,2019,14(3):228-236.
[55]	Huang L, Zheng J, Sun G, et al. 5-Aminosalicylic acid ameliorates dextran sulfate sodium-induced colitis in mice by modulating gut microbiota and bile acid metabolism[J]. Cell Mol Life Sci,2022,79(8):460.
[56]	Zhong G, Shi R, Chen Q, et al. Metabolomics reveals the potential metabolic mechanism of infliximab against DSS-induced acute and chronic ulcerative colitis[J]. Naunyn Schmiedebergs Arch Pharmacol,2024,397(11):8815-8824.
[57]	Zhang Y, Han L, Dong J, et al. Shaoyao decoction improves damp-heat colitis by activating the AHR/IL-22/STAT3 pathway through tryptophan metabolism driven by gut microbiota[J]. J Ethnopharmacol,2024,326:117874.
[58]	Wan L, Qian C, Yang C, et al. Ginseng polysaccharides ameliorate ulcerative colitis via regulating gut microbiota and tryptophan metabolism[J]. Int J Biol Macromol,2024,265(Pt 2):130822.
[59]	Zou Y, Ding W, Wu Y, et al. Puerarin alleviates inflammation and pathological damage in colitis mice by regulating metabolism and gut microbiota[J]. Front Microbiol,2023,14:1279029.
[60]	Jing W, Dong S, Xu Y, et al. Gut microbiota-derived tryptophan metabolites regulated by Wuji Wan to attenuate colitis through AhR signaling activation[J]. Acta Pharm Sin B,2025,15(1):205-223.
[61]	Xu D, Wu Q, Liu W, et al. Therapeutic efficacy and underlying mechanisms of Gastrodia elata polysaccharides on dextran sulfate sodium-induced inflammatory bowel disease in mice: Modulation of the gut microbiota and improvement of metabolic disorders[J]. Int J Biol Macromol,2023,248:125919.

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Research progress on ulcerative colitis based on tryptophan metabolism

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