Estrogens Play a Critical Role in Stress-Related Gastrointestinal Dysfunction in a Spontaneous Model of Disorders of Gut–Brain Interaction
Background: Disorders of the gut–brain interaction (DGBI), such as irritable bowel syndrome and functional dyspepsia, are more prevalent in women than in men, with a ratio of 2:1. Furthermore, stressful life events have been reported as one of the triggers for symptoms in DGBI patients. Methods: Her...
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MDPI AG
2022-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/7/1214 |
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| author | Alison Accarie Joran Toth Lucas Wauters Ricard Farré Jan Tack Tim Vanuytsel |
| author_facet | Alison Accarie Joran Toth Lucas Wauters Ricard Farré Jan Tack Tim Vanuytsel |
| author_sort | Alison Accarie |
| collection | DOAJ |
| description | Background: Disorders of the gut–brain interaction (DGBI), such as irritable bowel syndrome and functional dyspepsia, are more prevalent in women than in men, with a ratio of 2:1. Furthermore, stressful life events have been reported as one of the triggers for symptoms in DGBI patients. Methods: Here, we studied the effect of an early-life stressor (maternal separation (MS)) on jejunal and colonic alterations, including colonic sensitivity and immune cells infiltration and activation in a validated spontaneous model of DGBI (BBDP-N), and investigated the involvement of β-estradiol on stress-worsened intestinal alterations. Results: We found that maternal separation exacerbated colonic sensitivity and mast cell and eosinophil infiltration and activation in females only. Ovariectomy partially rescued the stress phenotype by decreasing colonic sensitivity, which was restored by β-estradiol injections and did not impact immune cells infiltration and activation. Stressed males exposed to β-estradiol demonstrated similar intestinal alterations as MS females. Conclusion: Estrogen plays a direct critical role in colonic hypersensitivity in a spontaneous animal model of DGBI, while for immune activation, estrogen seems to be involved in the first step of their recruitment and activation. Our data point towards a complex interaction between stress and β-estradiol in DGBI. |
| first_indexed | 2024-03-09T12:00:04Z |
| format | Article |
| id | doaj.art-e22be7ab8b2a4f2db485fe60dde09ba4 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T12:00:04Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-e22be7ab8b2a4f2db485fe60dde09ba42023-11-30T23:05:03ZengMDPI AGCells2073-44092022-04-01117121410.3390/cells11071214Estrogens Play a Critical Role in Stress-Related Gastrointestinal Dysfunction in a Spontaneous Model of Disorders of Gut–Brain InteractionAlison Accarie0Joran Toth1Lucas Wauters2Ricard Farré3Jan Tack4Tim Vanuytsel5Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (ChroMetA), KU Leuven, 3000 Leuven, BelgiumTranslational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (ChroMetA), KU Leuven, 3000 Leuven, BelgiumTranslational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (ChroMetA), KU Leuven, 3000 Leuven, BelgiumTranslational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (ChroMetA), KU Leuven, 3000 Leuven, BelgiumTranslational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (ChroMetA), KU Leuven, 3000 Leuven, BelgiumTranslational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (ChroMetA), KU Leuven, 3000 Leuven, BelgiumBackground: Disorders of the gut–brain interaction (DGBI), such as irritable bowel syndrome and functional dyspepsia, are more prevalent in women than in men, with a ratio of 2:1. Furthermore, stressful life events have been reported as one of the triggers for symptoms in DGBI patients. Methods: Here, we studied the effect of an early-life stressor (maternal separation (MS)) on jejunal and colonic alterations, including colonic sensitivity and immune cells infiltration and activation in a validated spontaneous model of DGBI (BBDP-N), and investigated the involvement of β-estradiol on stress-worsened intestinal alterations. Results: We found that maternal separation exacerbated colonic sensitivity and mast cell and eosinophil infiltration and activation in females only. Ovariectomy partially rescued the stress phenotype by decreasing colonic sensitivity, which was restored by β-estradiol injections and did not impact immune cells infiltration and activation. Stressed males exposed to β-estradiol demonstrated similar intestinal alterations as MS females. Conclusion: Estrogen plays a direct critical role in colonic hypersensitivity in a spontaneous animal model of DGBI, while for immune activation, estrogen seems to be involved in the first step of their recruitment and activation. Our data point towards a complex interaction between stress and β-estradiol in DGBI.https://www.mdpi.com/2073-4409/11/7/1214multifactorial DGBI modelβ-estradioldisorders of gut–brain interactionirritable bowel syndromemast cellsvisceral hypersensitivity |
| spellingShingle | Alison Accarie Joran Toth Lucas Wauters Ricard Farré Jan Tack Tim Vanuytsel Estrogens Play a Critical Role in Stress-Related Gastrointestinal Dysfunction in a Spontaneous Model of Disorders of Gut–Brain Interaction Cells multifactorial DGBI model β-estradiol disorders of gut–brain interaction irritable bowel syndrome mast cells visceral hypersensitivity |
| title | Estrogens Play a Critical Role in Stress-Related Gastrointestinal Dysfunction in a Spontaneous Model of Disorders of Gut–Brain Interaction |
| title_full | Estrogens Play a Critical Role in Stress-Related Gastrointestinal Dysfunction in a Spontaneous Model of Disorders of Gut–Brain Interaction |
| title_fullStr | Estrogens Play a Critical Role in Stress-Related Gastrointestinal Dysfunction in a Spontaneous Model of Disorders of Gut–Brain Interaction |
| title_full_unstemmed | Estrogens Play a Critical Role in Stress-Related Gastrointestinal Dysfunction in a Spontaneous Model of Disorders of Gut–Brain Interaction |
| title_short | Estrogens Play a Critical Role in Stress-Related Gastrointestinal Dysfunction in a Spontaneous Model of Disorders of Gut–Brain Interaction |
| title_sort | estrogens play a critical role in stress related gastrointestinal dysfunction in a spontaneous model of disorders of gut brain interaction |
| topic | multifactorial DGBI model β-estradiol disorders of gut–brain interaction irritable bowel syndrome mast cells visceral hypersensitivity |
| url | https://www.mdpi.com/2073-4409/11/7/1214 |
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