PDF(Pubmed)
Abstract：
Adenomatous polyps (APs) with inflammation are risk factors for colorectal cancer. However, the role of inflammation-related gut microbiota in promoting the progression of APs is unknown.
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.
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.
摘要：
背景：伴有炎症的腺瘤性息肉（AP）是结直肠癌的危险因素。然而,炎症相关的肠道菌群在促进AP进展中的作用尚不清楚.
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。
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。
