Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran.
Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.
Indian J Gastroenterol. 2024 Aug;43(4):832-840. doi: 10.1007/s12664-024-01605-2. Epub 2024 Jun 14.
Dysregulation of cytokines and intestinal mycobiome has been surveyed in the progression of inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD). On the other hand, the intestinal fungal flora and its main receptor, Dectin-1, induce immune-derived cytokines.
Total 64 individuals comprising 32 patients with UC (case group) and 32 healthy subjects (HS group) were assessed. The type and prevalence of fecal yeast species were determined by deoxyribonucleic acid (DNA) sequencing through polymerase chain reaction (PCR) amplification using ITS4 and ITS5 primers. Furthermore, the ribonucleic acid (RNAs) of IL-4, IL-10, IL-17, IL-22 and IFN-γ were extracted. The expression of Dectin-1 gene was then measured in the excised tissue samples.
A higher global fungal load in UC-affected patients (75%) was found in comparison with the HS group (25%), especially Candida albicans. Saccharomyces cerevisiae was significantly reduced in the fecal samples of UC-affected patients compared to HS (15.04% vs. 1.93% UC). The expression level of Dectin-1 was significantly elevated in patients with active UC (7.37 ± 0.81) than in patients with non-active UC (5.01 ± 77.25) and healthy controls (0.97 ± 0.24) (p < 0.05). The expression levels of IL-4, IL-10, especially both IL-17 and IL-22, were higher in the active UC group compared to the HS group (p = 0.0101, p = 0.0155, p < 0.0001, p < 0.0001, respectively). Similar expression level of IL-4, IL-10, IL-17, IL-22 (p > 0.999) and lower expression of interferongamma (IFN-γ) (p = 0.0021) were found in the non-active UC group compared to the HS group. A significant weak to moderate correlation was detected between Dectin-1 and IL-17 (r = 0.339, p = 0.019), as well as Dectin-1 and IL-22 (r = 0.373, p = 0.015). Furthermore, the expression levels of Dectin-1, IL-17 and IL-22 displayed significant associations with disease activity (p < 0.001, p = 0.029 and p = 0.003, respectively), regardless of the participant group.
The current study revealed a possible role for intestinal fungi to promote colonic inflammation and increase UC activity through Dectin-1 stimulation. A positive correlation was detected between intestinal fungal richness with UC susceptibility and activity. IL-4 and IL-10 were associated with disease activity. Besides, the expression levels of Dectin-1, IL-17 and IL-22 were independently associated with disease activity.
细胞因子和肠道真菌群落的失调已在炎症性肠病（IBD）的进展中进行了研究，包括溃疡性结肠炎（UC）和克罗恩病（CD）。另一方面，肠道真菌菌群及其主要受体 Dectin-1 可诱导免疫源性细胞因子。
共纳入 64 名个体，包括 32 名 UC 患者（病例组）和 32 名健康受试者（HS 组）。通过聚合酶链反应（PCR）扩增使用 ITS4 和 ITS5 引物，通过脱氧核糖核酸（DNA）测序确定粪便酵母种类的类型和流行率。此外，提取白细胞介素 4（IL-4）、白细胞介素 10（IL-10）、白细胞介素 17（IL-17）、白细胞介素 22（IL-22）和干扰素γ（IFN-γ）的核糖核酸（RNA）。然后测量切除组织样本中的 Dectin-1 基因的表达。
与 HS 组（25%）相比，UC 患者的肠道真菌总负荷更高（75%），尤其是白色念珠菌。与 HS 相比，UC 患者粪便样本中的酿酒酵母显著减少（15.04%比 UC 中的 1.93%）。与非活动 UC 患者（5.01±77.25）和健康对照组（0.97±0.24）相比，活动 UC 患者的 Dectin-1 表达水平明显升高（7.37±0.81）（p<0.05）。与 HS 组相比，活动 UC 组的白细胞介素 4（IL-4）、白细胞介素 10 表达水平更高，尤其是白细胞介素 17（IL-17）和白细胞介素 22（IL-22）（p=0.0101，p=0.0155，p<0.0001，p<0.0001，分别）。与 HS 组相比，非活动 UC 组的白细胞介素 4（IL-4）、白细胞介素 10（IL-10）、白细胞介素 17（IL-17）、白细胞介素 22（IL-22）表达水平相似（p>0.999），干扰素γ（IFN-γ）表达水平较低（p=0.0021）。在 Dectin-1 和白细胞介素 17（r=0.339，p=0.019）以及 Dectin-1 和白细胞介素 22（r=0.373，p=0.015）之间检测到显著的弱到中度相关性。此外，Dectin-1、白细胞介素 17 和白细胞介素 22 的表达水平与疾病活动度显著相关（p<0.001、p=0.029 和 p=0.003，分别），无论参与者组如何。
本研究表明，肠道真菌可能通过 Dectin-1 刺激促进结肠炎症和增加 UC 活动。肠道真菌丰富度与 UC 易感性和活动度呈正相关。白细胞介素 4（IL-4）和白细胞介素 10（IL-10）与疾病活动度相关。此外，Dectin-1、白细胞介素 17（IL-17）和白细胞介素 22（IL-22）的表达水平与疾病活动度独立相关。
