Indole-3-lactic acid suppresses colorectal cancer via metabolic reprogramming
Research indicates that abnormal gut microbiota metabolism is linked to colorectal cancer (CRC) progression, but the role of microbiota-related tryptophan metabolism disruption remains unclear. Using metagenomic sequencing and targeted Trp metabolomics, our research identified that CRC patients had...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2025.2508949 |
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| author | Shizhen Zhou Kai Wang Jiandong Huang Zhen Xu Qinggang Yuan Lixiang Liu Zhifeng Wang Ji Miao Hao Wang Tingting Wang Wenxian Guan Chao Ding |
| author_facet | Shizhen Zhou Kai Wang Jiandong Huang Zhen Xu Qinggang Yuan Lixiang Liu Zhifeng Wang Ji Miao Hao Wang Tingting Wang Wenxian Guan Chao Ding |
| author_sort | Shizhen Zhou |
| collection | DOAJ |
| description | Research indicates that abnormal gut microbiota metabolism is linked to colorectal cancer (CRC) progression, but the role of microbiota-related tryptophan metabolism disruption remains unclear. Using metagenomic sequencing and targeted Trp metabolomics, our research identified that CRC patients had abnormal indole-3-lactic acid (ILA) levels, which were related to tumor malignancy. Exogenous ILA administration suppressed CRC development in AOM/DSS induced and xenograft mice models. Furthermore, in vitro experiments demonstrated that ILA inhibits tumor cell proliferation, migration, and anti-apoptotic capabilities. Mechanistically, ILA appears to directly occupy the phosphorylation sites of STAT3, leading to a reduction in intracellular phosphorylated STAT3 (p-STAT3) levels and the inhibition of the HK2 pathway, thereby downregulating glucose metabolism in cancer cells. Notably, this inhibition is independent of the aryl hydrocarbon receptor (AHR). In conclusion, our research findings demonstrate that alterations in tryptophan metabolism among CRC patients can influence tumor progression and reveal a novel mechanism through which ILA exerts its inhibitory effects on CRC. These findings offer new insights into the role of gut microbiota in CRC and identify potential clinical therapeutic targets. |
| format | Article |
| id | doaj-art-d6b2d5fbcb7a4fc5a449ddc12bbcf620 |
| institution | DOAJ |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-d6b2d5fbcb7a4fc5a449ddc12bbcf6202025-08-20T03:13:43ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2508949Indole-3-lactic acid suppresses colorectal cancer via metabolic reprogrammingShizhen Zhou0Kai Wang1Jiandong Huang2Zhen Xu3Qinggang Yuan4Lixiang Liu5Zhifeng Wang6Ji Miao7Hao Wang8Tingting Wang9Wenxian Guan10Chao Ding11Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaThe State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China01life Institute, Shenzhen, ChinaThe State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, ChinaDepartment of Gastrointestinal Surgery, Xuzhou Central Hospital, Xuzhou, ChinaDepartment of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China01life Institute, Shenzhen, ChinaDepartment of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDepartment of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaThe State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, ChinaDepartment of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDepartment of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaResearch indicates that abnormal gut microbiota metabolism is linked to colorectal cancer (CRC) progression, but the role of microbiota-related tryptophan metabolism disruption remains unclear. Using metagenomic sequencing and targeted Trp metabolomics, our research identified that CRC patients had abnormal indole-3-lactic acid (ILA) levels, which were related to tumor malignancy. Exogenous ILA administration suppressed CRC development in AOM/DSS induced and xenograft mice models. Furthermore, in vitro experiments demonstrated that ILA inhibits tumor cell proliferation, migration, and anti-apoptotic capabilities. Mechanistically, ILA appears to directly occupy the phosphorylation sites of STAT3, leading to a reduction in intracellular phosphorylated STAT3 (p-STAT3) levels and the inhibition of the HK2 pathway, thereby downregulating glucose metabolism in cancer cells. Notably, this inhibition is independent of the aryl hydrocarbon receptor (AHR). In conclusion, our research findings demonstrate that alterations in tryptophan metabolism among CRC patients can influence tumor progression and reveal a novel mechanism through which ILA exerts its inhibitory effects on CRC. These findings offer new insights into the role of gut microbiota in CRC and identify potential clinical therapeutic targets.https://www.tandfonline.com/doi/10.1080/19490976.2025.2508949Indole-3-lactic acidHK2P-STAT3glycolysiscolorectal cancer |
| spellingShingle | Shizhen Zhou Kai Wang Jiandong Huang Zhen Xu Qinggang Yuan Lixiang Liu Zhifeng Wang Ji Miao Hao Wang Tingting Wang Wenxian Guan Chao Ding Indole-3-lactic acid suppresses colorectal cancer via metabolic reprogramming Gut Microbes Indole-3-lactic acid HK2 P-STAT3 glycolysis colorectal cancer |
| title | Indole-3-lactic acid suppresses colorectal cancer via metabolic reprogramming |
| title_full | Indole-3-lactic acid suppresses colorectal cancer via metabolic reprogramming |
| title_fullStr | Indole-3-lactic acid suppresses colorectal cancer via metabolic reprogramming |
| title_full_unstemmed | Indole-3-lactic acid suppresses colorectal cancer via metabolic reprogramming |
| title_short | Indole-3-lactic acid suppresses colorectal cancer via metabolic reprogramming |
| title_sort | indole 3 lactic acid suppresses colorectal cancer via metabolic reprogramming |
| topic | Indole-3-lactic acid HK2 P-STAT3 glycolysis colorectal cancer |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2025.2508949 |
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