Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：已经在炎症性肠病（IBDs）的进展中调查了细胞因子和肠道真菌群的失调，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诱导免疫衍生的细胞因子。
方法：对包括32名UC患者（病例组）和32名健康受试者（HS组）在内的64名个体进行评估。通过使用ITS4和ITS5引物的聚合酶链反应（PCR）扩增，通过脱氧核糖核酸（DNA）测序确定粪便酵母的类型和患病率。此外，提取IL-4、IL-10、IL-17、IL-22和IFN-γ的核糖核酸(RNA)。然后在切除的组织样品中测量Dectin-1基因的表达。
结果：与HS组（25％）相比，UC患者（75％）的整体真菌负荷更高，尤其是白色念珠菌.与HS相比，UC患者的粪便样本中酿酒酵母显着减少（15.04％vs.1.93%UC）。Dectin-1在活动性UC患者中的表达水平(7.37±0.81)高于非活动性UC患者(5.01±77.25)和健康对照组(0.97±0.24)(p<0.05)。IL-4、IL-10,尤其是IL-17和IL-22的表达水平在活动性UC组中高于HS组(分别为p=0.0101,p=0.0155,p<0.0001,p<0.0001)。与HS组相比,在非活性UC组中发现了相似的IL-4、IL-10、IL-17、IL-22表达水平(p>0.999)和较低的干扰素(IFN-γ)表达(p=0.0021)。Dectin-1和IL-17之间检测到显著的弱至中度相关性(r=0.339,p=0.019),以及Dectin-1和IL-22（r=0.373，p=0.015）。此外，Dectin-1，IL-17和IL-22的表达水平与疾病活动性显着相关（分别为p<0.001，p=0.029和p=0.003），无论参与者是谁。
结论：目前的研究揭示了肠道真菌通过Dectin-1刺激促进结肠炎症和增加UC活性的可能作用。肠道真菌丰富度与UC易感性和活性呈正相关。IL-4和IL-10与疾病活动性有关。此外,Dectin-1，IL-17和IL-22的表达水平与疾病活动性独立相关。
方法：对包括32名UC患者（病例组）和32名健康受试者（HS组）在内的64名个体进行评估。通过使用ITS4和ITS5引物的聚合酶链反应（PCR）扩增，通过脱氧核糖核酸（DNA）测序确定粪便酵母的类型和患病率。此外，提取IL-4、IL-10、IL-17、IL-22和IFN-γ的核糖核酸(RNA)。然后在切除的组织样品中测量Dectin-1基因的表达。
结果：与HS组（25％）相比，UC患者（75％）的整体真菌负荷更高，尤其是白色念珠菌.与HS相比，UC患者的粪便样本中酿酒酵母显着减少（15.04％vs.1.93%UC）。Dectin-1在活动性UC患者中的表达水平(7.37±0.81)高于非活动性UC患者(5.01±77.25)和健康对照组(0.97±0.24)(p<0.05)。IL-4、IL-10,尤其是IL-17和IL-22的表达水平在活动性UC组中高于HS组(分别为p=0.0101,p=0.0155,p<0.0001,p<0.0001)。与HS组相比,在非活性UC组中发现了相似的IL-4、IL-10、IL-17、IL-22表达水平(p>0.999)和较低的干扰素(IFN-γ)表达(p=0.0021)。Dectin-1和IL-17之间检测到显著的弱至中度相关性(r=0.339,p=0.019),以及Dectin-1和IL-22（r=0.373，p=0.015）。此外，Dectin-1，IL-17和IL-22的表达水平与疾病活动性显着相关（分别为p<0.001，p=0.029和p=0.003），无论参与者是谁。
结论：目前的研究揭示了肠道真菌通过Dectin-1刺激促进结肠炎症和增加UC活性的可能作用。肠道真菌丰富度与UC易感性和活性呈正相关。IL-4和IL-10与疾病活动性有关。此外,Dectin-1，IL-17和IL-22的表达水平与疾病活动性独立相关。
