Association between AHR in EGCs and IBS-D patients: the indole pathway of tryptophan metabolism
BackgroundThe pathophysiological mechanisms of irritable bowel syndrome (IBS) are intricate, and associated with tryptophan metabolites. This study was designed to investigate the relationship between indole metabolites in the feces and intestinal function in patients with IBS.MethodsIn this study,...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2025.1566595/full |
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| author | Lianli Wang Yue Zhang Yan Ran Laifu Li Lin Mei Fangchen Ye Yating Sun Ting Wang Xiaojing Quan Haitao Shi Fei Dai |
| author_facet | Lianli Wang Yue Zhang Yan Ran Laifu Li Lin Mei Fangchen Ye Yating Sun Ting Wang Xiaojing Quan Haitao Shi Fei Dai |
| author_sort | Lianli Wang |
| collection | DOAJ |
| description | BackgroundThe pathophysiological mechanisms of irritable bowel syndrome (IBS) are intricate, and associated with tryptophan metabolites. This study was designed to investigate the relationship between indole metabolites in the feces and intestinal function in patients with IBS.MethodsIn this study, 42 patients with diarrhea-predominant IBS (IBS-D) and 36 healthy controls were recruited. The symptom severity was evaluated using IBS-quality of life (IBS-QOL) and IBS symptom severity system (IBS-SSS). The levels of indole metabolite in fecal samples were determined by means of mass spectrometry. Colon mucosal tissues were collected during colonoscopy procedures. Immunohistochemistry or immunofluorescence techniques were employed to analyze the expressions of the aryl hydrocarbon receptor (AHR), cytochrome P450 1A1 (CYP1A1), glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), zonula occludens-1 (Zo-1), occludin, substance P (SP), nerve growth factor (NGF), NOD-like receptor family pyrin domain containing 3 (NLRP3), and nuclear factor kappa B (NF-κB) in the mucosal tissues.ResultsCompared with healthy controls, the concentrations of the main indole metabolites (p = 0.020), and the expressions of CYP1A1 (p < 0.001), and Zo-1 (p = 0.017) were decreased in patients with IBS-D, but the expressions of S100B (p < 0.001), NF-κB (p = 0.006), and NRLP3 (p = 0.041) were increased. Immunofluorescence analysis demonstrated the co-expression of AHR with GFAP or S100B. Moreover, the ratio of S100B/AHR (p = 0.011) was higher in IBS-D patients than in health controls. This ratio was positively correlated with IBS-SSS score (r = 0.47, p = 0.006), as well as with the expression levels of NRLP3 (r = 0.505, p = 0.019), NF-κB (r = 0.548, p = 0.01), and SP (r = 0.832, p < 0.01).ConclusionPatients with IBS-D exhibited low-grade inflammation in the colon mucosal tissues, compromised intestinal barrier function, and abnormal visceral sensation. This may be attributed to the decreased levels of tryptophan indole metabolites, the heightened activity of enteric glial cells (EGCs), and the inhibition of AHR/CPY1A1 signaling pathway. |
| format | Article |
| id | doaj-art-d2739633be4c4d61ba5a7b718c14b034 |
| institution | DOAJ |
| issn | 2296-861X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj-art-d2739633be4c4d61ba5a7b718c14b0342025-08-20T02:48:33ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2025-03-011210.3389/fnut.2025.15665951566595Association between AHR in EGCs and IBS-D patients: the indole pathway of tryptophan metabolismLianli Wang0Yue Zhang1Yan Ran2Laifu Li3Lin Mei4Fangchen Ye5Yating Sun6Ting Wang7Xiaojing Quan8Haitao Shi9Fei Dai10Division of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDivision of Gastroenterology, Honghui Hospital, Xi’an Jiaotong University College of Medicine, Xi’an, ChinaDivision of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDivision of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDivision of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDivision of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDivision of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDivision of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDivision of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDivision of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDivision of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaBackgroundThe pathophysiological mechanisms of irritable bowel syndrome (IBS) are intricate, and associated with tryptophan metabolites. This study was designed to investigate the relationship between indole metabolites in the feces and intestinal function in patients with IBS.MethodsIn this study, 42 patients with diarrhea-predominant IBS (IBS-D) and 36 healthy controls were recruited. The symptom severity was evaluated using IBS-quality of life (IBS-QOL) and IBS symptom severity system (IBS-SSS). The levels of indole metabolite in fecal samples were determined by means of mass spectrometry. Colon mucosal tissues were collected during colonoscopy procedures. Immunohistochemistry or immunofluorescence techniques were employed to analyze the expressions of the aryl hydrocarbon receptor (AHR), cytochrome P450 1A1 (CYP1A1), glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), zonula occludens-1 (Zo-1), occludin, substance P (SP), nerve growth factor (NGF), NOD-like receptor family pyrin domain containing 3 (NLRP3), and nuclear factor kappa B (NF-κB) in the mucosal tissues.ResultsCompared with healthy controls, the concentrations of the main indole metabolites (p = 0.020), and the expressions of CYP1A1 (p < 0.001), and Zo-1 (p = 0.017) were decreased in patients with IBS-D, but the expressions of S100B (p < 0.001), NF-κB (p = 0.006), and NRLP3 (p = 0.041) were increased. Immunofluorescence analysis demonstrated the co-expression of AHR with GFAP or S100B. Moreover, the ratio of S100B/AHR (p = 0.011) was higher in IBS-D patients than in health controls. This ratio was positively correlated with IBS-SSS score (r = 0.47, p = 0.006), as well as with the expression levels of NRLP3 (r = 0.505, p = 0.019), NF-κB (r = 0.548, p = 0.01), and SP (r = 0.832, p < 0.01).ConclusionPatients with IBS-D exhibited low-grade inflammation in the colon mucosal tissues, compromised intestinal barrier function, and abnormal visceral sensation. This may be attributed to the decreased levels of tryptophan indole metabolites, the heightened activity of enteric glial cells (EGCs), and the inhibition of AHR/CPY1A1 signaling pathway.https://www.frontiersin.org/articles/10.3389/fnut.2025.1566595/fulltryptophanaryl hydrocarbon receptorinflammationenteric glial cellsIBS-D |
| spellingShingle | Lianli Wang Yue Zhang Yan Ran Laifu Li Lin Mei Fangchen Ye Yating Sun Ting Wang Xiaojing Quan Haitao Shi Fei Dai Association between AHR in EGCs and IBS-D patients: the indole pathway of tryptophan metabolism Frontiers in Nutrition tryptophan aryl hydrocarbon receptor inflammation enteric glial cells IBS-D |
| title | Association between AHR in EGCs and IBS-D patients: the indole pathway of tryptophan metabolism |
| title_full | Association between AHR in EGCs and IBS-D patients: the indole pathway of tryptophan metabolism |
| title_fullStr | Association between AHR in EGCs and IBS-D patients: the indole pathway of tryptophan metabolism |
| title_full_unstemmed | Association between AHR in EGCs and IBS-D patients: the indole pathway of tryptophan metabolism |
| title_short | Association between AHR in EGCs and IBS-D patients: the indole pathway of tryptophan metabolism |
| title_sort | association between ahr in egcs and ibs d patients the indole pathway of tryptophan metabolism |
| topic | tryptophan aryl hydrocarbon receptor inflammation enteric glial cells IBS-D |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2025.1566595/full |
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