Academic Journal
Quantifying the impact of gut microbiota on inflammation and hypertensive organ damage
| العنوان: | Quantifying the impact of gut microbiota on inflammation and hypertensive organ damage |
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| المؤلفون: | Avery, E.G., Bartolomaeus, H., Rauch, A., Chen, C.Y., N'Diaye, G., Löber, U., Bartolomaeus, T.U.P., Fritsche-Guenther, R., Rodrigues, A.F., Yarritu, A., Zhong, C., Fei, L., Tsvetkov, D., Todiras, M., Park, J.K., Markó, L., Maifeld, A., Patzak, A., Bader, M., Kempa, S., Kirwan, J.A., Forslund, S.K., Müller, D.N., Wilck, N. |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2023 |
| المجموعة: | Max-Delbrueck-Center for Molecular Medicine, Berlin: MDC Repository |
| مصطلحات موضوعية: | Cardiovascular and Metabolic Diseases, Technology Platforms, Topic 1: Genes, Cells and Cell-Based Medicine, Topic 3: Integrative Biomedicine |
| الوصف: | AIMS: Hypertension (HTN) can lead to heart and kidney damage. The gut microbiota has been linked to HTN, although it is difficult to estimate its significance due to the variety of other features known to influence HTN. In the present study, we used germ-free (GF) and colonized (COL) littermate mice to quantify the impact of microbial colonization on organ damage in HTN. METHODS AND RESULTS: Four-week-old male GF C57BL/6J littermates were randomized to remain GF or receive microbial colonization. HTN was induced by subcutaneous infusion with angiotensin (Ang) II (1.44 mg/kg/d) and 1% NaCl in the drinking water; sham-treated mice served as control. Renal damage was exacerbated in GF mice, whereas cardiac damage was more comparable between COL and GF, suggesting that the kidney is more sensitive to microbial influence. Multivariate analysis revealed a larger effect of HTN in GF mice. Serum metabolomics demonstrated that the colonization status influences circulating metabolites relevant to HTN. Importantly, GF mice were deficient in anti-inflammatory fecal short-chain fatty acids (SCFA). Flow cytometry showed that the microbiome has an impact on the induction of anti-hypertensive myeloid-derived suppressor cells and pro-inflammatory Th17 cells in HTN. In vitro inducibility of Th17 cells was significantly higher for cells isolated from GF than conventionally raised mice. CONCLUSIONS: Microbial colonization status of mice had potent effects on their phenotypic response to a hypertensive stimulus, and the kidney is a highly microbiota-susceptible target organ in HTN. The magnitude of the pathogenic response in GF mice underscores the role of the microbiome in mediating inflammation in HTN. TRANSLATION PERSPECTIVE: To assess the potential of microbiota-targeted interventions to prevent organ damage in hypertension, an accurate quantification of microbial influence is necessary. We provide evidence that the development of hypertensive organ damage is dependent on colonization status and suggest that a healthy ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf; other |
| اللغة: | English |
| Relation: | http://edoc.mdc-berlin.de/21968/1/21968oa.pdf; http://edoc.mdc-berlin.de/21968/7/21968suppl.zip; Quantifying the impact of gut microbiota on inflammation and hypertensive organ damage. Avery, E.G. and Bartolomaeus, H. and Rauch, A. and Chen, C.Y. and N'Diaye, G. and Löber, U. and Bartolomaeus, T.U.P. and Fritsche-Guenther, R. and Rodrigues, A.F. and Yarritu, A. and Zhong, C. and Fei, L. and Tsvetkov, D. and Todiras, M. and Park, J.K. and Markó, L. and Maifeld, A. and Patzak, A. and Bader, M. and Kempa, S. and Kirwan, J.A. and Forslund, S.K. and Müller, D.N. and Wilck, N. Cardiovascular Research 119 (6): 1441-1452. May 2023 |
| DOI: | 10.1093/cvr/cvac121 |
| الاتاحة: | http://edoc.mdc-berlin.de/21968/ https://edoc.mdc-berlin.de/21968/ http://edoc.mdc-berlin.de/21968/1/21968oa.pdf http://edoc.mdc-berlin.de/21968/7/21968suppl.zip https://doi.org/10.1093/cvr/cvac121 |
| Rights: | cc_by_nc_4 |
| رقم الانضمام: | edsbas.F10D9058 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/cvr/cvac121 |
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