中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (10): 2413-2421.doi: 10.12307/2026.615

• 骨组织构建 bone tissue construction •    下一篇

肠道菌群色氨酸代谢产物吲哚-3-丙酸改善炎症性肠病模型小鼠的骨质疏松症

邱学力1，崔  浩1，2，吴晨阳1，陶理德1，姚宇倩1，田  波1，白进玉1，张应子1   

  1. 1苏州大学附属第二医院骨科，江苏省苏州市  215004；2苏州大学苏州医学院，江苏省苏州市  215004

  • 收稿日期:2025-02-20 接受日期:2025-06-11 出版日期:2026-04-08 发布日期:2025-08-27
  • 通讯作者: 张应子，副主任医师，副教授，硕士生导师，苏州大学附属第二医院骨科，江苏省苏州市 215004
  • 作者简介:邱学力，男，1999年生，浙江省湖州市人，汉族，苏州大学在读硕士，主要从事骨代谢相关研究。 共同第一作者：崔浩，男，2001年生，江苏省徐州市人，汉族，苏州大学在读本科。
  • 基金资助:
    苏州市姑苏卫生人才项目[(2022)161]及科研基金(GSWS2022041)，项目负责人：张应子；中核医疗“核医创新”项目(ZHYLYB2021005)，项目负责人：张应子；江苏省卫生健康委员会科研项目(H2023139)，项目负责人：张应子；中核集团青年英才菁英项目，项目负责人：张应子；苏州大学仲英青年学者项目，项目负责人：张应子；江苏省研究生科研与实践创新计划项目(KYCX24_3344)，项目主持人：邱学力，指导老师：张应子

Gut microbiota tryptophan metabolite indole-3-propionic acid alleviates inflammatory bowel disease-related osteoporosis in a mouse model 

Qiu Xueli1, Cui Hao1, 2, Wu Chenyang1, Tao Lide1, Yao Yuqian1, Tian Bo1, Bai Jinyu1, Zhang Yingzi1   

  1. 1Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China; 2Suzhou Medical College of Soochow University, Suzhou 215004, Jiangsu Province, China

  • Received:2025-02-20 Accepted:2025-06-11 Online:2026-04-08 Published:2025-08-27
  • Contact: Zhang Yingzi, Associate chief physician, Associate professor, Master’s supervisor, Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China
  • About author:Qiu Xueli, MS candidate, Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China Cui Hao, Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China; Suzhou Medical College of Soochow University, Suzhou 215004, Jiangsu Province, China Qiu Xueli and Cui Hao contributed equally to this work.
  • Supported by:
    Gusu Health Talent Program of Suzhou, No. (2022)161 (to ZYZ); Gusu Scientific Research Fund of Suzhou, No. GSWS2022041 (to ZYZ); "Nuclear Medicine Innovation" Project of China National Nuclear Corporation, No. ZHYLYB2021005 (to ZYZ); Research Project of Jiangsu Provincial Health Commission, No. H2023139 (to ZYZ); Youth Talent Elite Program of China National Nuclear Corporation (to ZYZ); Zhongying Young Scholar Program of Soochow University (to ZYZ); Jiangsu Graduate Research and Practice Innovation Program, No. KYCX24_3344 (to QXL [project investigator] and ZYZ [supervisor])

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摘要：


文题释义：
肠道菌群：是指存在于动物和人类肠道中的微生物群落，它们在消化代谢、免疫调节和健康维持中发挥重要作用。调整肠道菌群(如使用益生菌、益生元或粪菌移植)已成为许多疾病的新型治疗策略之一。
炎症性肠病：是一类以慢性肠道炎症为特征的疾病，包括溃疡性结肠炎和克罗恩病。炎症性肠病的病因涉及遗传、环境、肠道菌群失调及免疫异常。
骨质疏松症：是一种以骨量减少、骨组织微结构退化、骨脆性增加和易发生骨折为特征的全身性代谢性骨病。

背景：肠-骨轴是指肠道微生物及其代谢产物通过调节宿主免疫、内分泌和代谢通路，影响骨骼发育、骨代谢和骨健康的相互作用网络，已有研究表明肠道菌群紊乱与炎症性肠病相关骨质疏松症互作。
目的：探讨肠道菌群色氨酸代谢产物吲哚-3-丙酸在炎症性肠病并发骨质疏松症中的保护作用及可能机制。
方法：6-8周龄雄性Balb/c小鼠随机分为对照组、模型组和吲哚-3-丙酸组，后2组在小鼠的饮用水中加入1.5%葡聚糖硫酸钠，连续饮用12周以诱导慢性肠炎，然后吲哚-3-丙酸组开始腹腔注射吲哚-3-丙酸(20 mg/kg)，每周3次，共4周。通过测量结肠长度、结肠组织苏木精-伊红染色及ELISA检测肠道炎症因子水平来评估肠道炎症程度；通过Micro-CT扫描分析骨量及骨微结构；通过股骨组织抗酒石酸酸性磷酸酶染色、苏木精-伊红染色、钙黄绿素双标实验及免疫荧光染色以评估成骨细胞、破骨细胞的活性及骨代谢状态。
结果与结论：①模型组小鼠结肠长度相比对照组缩短，吲哚-3-丙酸组小鼠结肠长度相比模型组增长；结肠苏木精-伊红染色结果显示模型组结肠结构破坏，隐窝排列紊乱并伴有大量炎症细胞浸润，吲哚-3-丙酸组肠道炎症细胞浸润显著减少，结肠结构恢复；②ELISA结果显示，与对照组相比，模型组小鼠肠道炎症因子水平显著升高(P < 0.000 1)；与模型组相比，吲哚-3-丙酸组炎症因子水平显著降低(P < 0.001)；③Micro-CT扫描及三维重建显示，吲哚-3-丙酸显著缓解了慢性肠炎小鼠骨量流失；④抗酒石酸酸性磷酸酶染色及苏木精-伊红染色显示，吲哚-3-丙酸组破骨细胞数量减少、骨小梁数目增加；钙黄绿素双标实验显示，吲哚-3-丙酸组骨形成能力提高；免疫荧光分析显示，吲哚-3-丙酸组SP7表达升高。以上结果说明，吲哚-3-丙酸通过减轻肠道炎症、抑制破骨细胞活性并上调成骨细胞功能来改善骨代谢，在炎症性肠病相关骨质疏松症治疗中具有潜在应用价值。

https://orcid.org/0009-0008-3115-8683(邱学力)；https://orcid.org/0009-0007-2786-5214(崔浩)

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 肠道菌群, 色氨酸代谢产物, 吲哚-3-丙酸, 炎症性肠病, 骨质疏松, 肠-骨轴, 骨代谢

Abstract: BACKGROUND: The gut-bone axis refers to the interaction network through which gut microbiota and its metabolites influence bone development, metabolism, and health by regulating host immune, endocrine, and metabolic pathways. Previous studies have demonstrated that disturbances in gut microbiota have been shown to interact with inflammatory bowel disease-associated osteoporosis.
OBJECTIVE: To investigate the protective effects and potential mechanisms of the gut microbiota tryptophan metabolite, indole-3-propionic acid, in inflammatory bowel disease combined with osteoporosis.
METHODS: Male Balb/c mice, aged 6-8 weeks, were randomly divided into three groups: control, model, and indole-3-propionic acid groups. In the latter two groups, 1.5% sodium dextran sulfate was added to the drinking water for 12 weeks to induce chronic enteritis, and then in the indole-3-propionic acid group, intraperitoneal injections of indole-3-propionic acid at a dose of 20 mg/kg were administered three times per week, for 4 weeks. Severity of colon inflammation was assessed by hematoxylin-eosin staining, colon length measurement, and ELISA detection of intestinal inflammatory cytokine levels. Bone mass and structure of the femur were analyzed by Micro-CT scanning. Viability of osteoblasts and osteoclasts and bone metabolism were assessed using tartrate-resistant acid phosphatase staining, hematoxylin-eosin staining, calcein double labeling and immunofluorescence staining. 
RESULTS AND CONCLUSION: (1) The colon length in the model group was shorter than that in the control group, while indole-3-propionic acid treatment improved the colon length. Hematoxylin-eosin staining of the colon showed that the model group exhibited disrupted colon structure, disordered crypt arrangement, and extensive infiltration of inflammatory cells. After the administration of indole-3-propionic acid, the infiltration of inflammatory cells was significantly reduced, and the colon structure was restored. (2) ELISA results indicated that the levels of intestinal inflammatory cytokines were significantly elevated in the model group compared with the control group (P < 0.000 1). After treatment with indole-3-propionic acid, the levels of intestinal inflammatory cytokines were significantly reduced (P < 0.001). (3) Micro-CT scanning and three-dimensional reconstruction showed that indole-3-propionic acid significantly alleviated bone loss in the mouse model of chronic enteritis. (4) Tartrate-resistant acid phosphatase staining and hematoxylin-eosin staining revealed that indole-3-propionic acid reduced the number of osteoclasts and increased the number of trabeculae. Calcein double labeling experiments showed that indole-3-propionic acid treatment improved bone formation capacity. Immunofluorescence analysis indicated that indole-3-propionic acid promoted the expression of SP7. These findings suggest that indole-3-propionic acid improves bone metabolism by reducing intestinal inflammation, inhibiting osteoclast activity, and upregulating osteoblast function, highlighting its potential application in the treatment of osteoporosis associated with inflammatory bowel disease.

Key words: gut microbiota, tryptophan metabolites, indole-3-propionic acid, inflammatory bowel disease, osteoporosis, gut-bone axis, bone metabolism 

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