Gut microbial metabolite TMAO increases peritoneal inflammation and peritonitis risk in peritoneal dialysis patients
| Autor: | Zhanmei Zhou, Haie Tang, Jianxia Hu, Gong Nirong, Liling Xie, Yunshi Lai, Xiaohong Zhong, Feifei Xie, Jianping Jiang, Lei Zhang, Fengxin Zhu, Miaomiao Zhou, Jing Nie, Jianwei Tian, Xinrong Zhang, Zheng Hu |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Adult
Male medicine.medical_specialty Necrosis medicine.medical_treatment Peritonitis CCL2 Epithelium Peritoneal dialysis Proinflammatory cytokine Rats Sprague-Dawley Methylamines Peritoneum Risk Factors Physiology (medical) Diabetes mellitus Internal medicine Human Umbilical Vein Endothelial Cells medicine Animals Humans Renal Insufficiency Chronic Inflammation Cell Death business.industry Biochemistry (medical) Public Health Environmental and Occupational Health General Medicine Middle Aged medicine.disease Gastrointestinal Microbiome Up-Regulation P-Selectin Glucose medicine.anatomical_structure Endocrinology Metabolome Cytokines Female Inflammation Mediators medicine.symptom business Peritoneal Dialysis Kidney disease |
| Zdroj: | Translational Research. 240:50-63 |
| ISSN: | 1931-5244 |
| DOI: | 10.1016/j.trsl.2021.10.001 |
| Popis: | Trimethylamine-N-oxide (TMAO), a gut microbiota-produced metabolite, is accumulated in chronic kidney disease (CKD) patients. It is well known to contribute to CKD-related cardiovascular complications. However, the effect of TMAO on peritoneal dialysis (PD)-related peritonitis remains largely unknown. Here, we demonstrate that serum concentrations of TMAO were positively correlated with C-reactive protein levels, and the appearance rate of dialysate IL-6 and PAI-1, in PD patients. During the follow-up period of 28.3 ± 8.0 months, patients with higher TMAO levels (≥50 μM) had a higher risk of new-onset peritonitis (HR, 3.60; 95%CI, 1.18-10.99; P=0.025) after adjusting for sex, age, diabetes, PD duration, BUN, rGFR, C-reactive protein, BMI and β2-M. In CKD rat models, TMAO significantly promoted peritoneal dialysate-induced inflammatory cell infiltration, inflammatory cytokines production in the peritoneum. In vitro study revealed that TMAO directly induced primary peritoneal mesothelial cell necrosis, together with increased production of pro-inflammatory cytokines including CCL2, TNF-α, IL-6, and IL-1β. In addition, TMAO significantly increased TNF-α-induced P-selectin production in mesothelial cells, as well as high glucose-induced TNF-α and CCL2 expression in endothelial cells. In conclusion, our data demonstrate that higher levels of TMAO exacerbate peritoneal inflammation and might be a risk factor of incidence of peritonitis in PD patients. |
| Databáze: | OpenAIRE |
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