Sequencing of the 16S rRNA gene was conducted to identify characteristic bacteria in AP tissues and normal mucosa. Then, the roles of inflammation-related bacteria were clarified by Spearman correlation analysis. Furthermore, colorectal HT-29 cells, normal colon NCM460 cells, and azoxymethane-treated mice were used to investigate the effects of the characteristic bacteria on progression of APs.
The expression levels of inflammation-related markers (diamine oxidase, D-lactate, C-reactive protein, tumor necrosis factor-α, interleukin-6 and interleukin-1β) were increased, whereas the expression levels of anti-inflammatory factors (interleukin-4 and interleukin-10) were significantly decreased in AP patients as compared to healthy controls. Solobacterium moorei (S. moorei) was enriched in AP tissues and fecal samples, and significantly positively correlated with serum inflammation-related markers. In vitro, S. moorei preferentially attached to HT-29 cells and stimulated cell proliferation and production of pro-inflammatory factors. In vivo, the incidence of intestinal dysplasia was significantly increased in the S. moorei group. Gavage of mice with S. moorei upregulated production of pro-inflammatory factors, suppressed proliferation of CD4+ and CD8+cells, and disrupted the integrity of the intestinal barrier, thereby accelerating progression of APs.
S. moorei accelerated the progression of AP in mice via activation of the NF-κB signaling pathway, chronic low-grade inflammation, and intestinal barrier disruption. Targeted reduction of S. moorei presents a potential strategy to prevent the progression of APs.
方法:进行16SrRNA基因测序,以鉴定AP组织和正常粘膜中的特征性细菌。然后,通过Spearman相关分析阐明炎症相关细菌的作用.此外,结直肠HT-29细胞,正常结肠NCM460细胞,和偶氮甲烷处理的小鼠用于研究特征细菌对AP进展的影响。
结果:炎症相关标志物的表达水平(二胺氧化酶,D-乳酸,C反应蛋白,肿瘤坏死因子-α,白细胞介素-6和白细胞介素-1β)增加,与健康对照组相比,AP患者的抗炎因子(白细胞介素-4和白细胞介素-10)的表达水平显着降低。Solobacteriummoorei(S.moorei)在AP组织和粪便样本中富集,与血清炎症相关指标呈显著正相关。体外,S.moorei优先附着于HT-29细胞并刺激细胞增殖和促炎因子的产生。在体内,S.moorei组肠道发育不良的发生率显著增加.用S.moorei灌胃小鼠可上调促炎因子的产生,抑制CD4+和CD8+细胞的增殖,破坏了肠道屏障的完整性,从而加速AP的进展。
结论:S.Moorei通过激活NF-κB信号通路加速小鼠AP的进展,慢性低度炎症,和肠屏障破坏。有针对性地减少S.moorei提出了预防AP进展的潜在策略。