Non-toxigenic Bacteroides fragilis (NTBF) administration reduces bacteria-driven chronic colitis and tumor development independent of polysaccharide A.
Non-toxigenic Bacteroides fragilis (NTBF) administration reduces bacteria-driven chronic colitis and tumor development independent of polysaccharide A.
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非毒性细菌片（NTBF）给药可降低细菌驱动的慢性结肠炎和肿瘤发育独立于多糖A。
DOI：
10.1038/s41385-018-0085-5
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发表时间：
2019-01
影响因子：
8
通讯作者：
Sears CL
中科院分区：
文献类型：
--
作者：
Chan JL;Wu S;Geis AL;Chan GV;Gomes TAM;Beck SE;Wu X;Fan H;Tam AJ;Chung L;Ding H;Wang H;Pardoll DM;Housseau F;Sears CL
多糖A(PSA)是非产毒脆弱类杆菌(NTBF)NCTC 9343菌株的一种免疫原性衣壳成分，具有促进粘膜免疫发育和抑制结肠炎的作用。相比之下，产肠毒素脆弱类杆菌(ETBF)与炎症性肠病(IBD)和结直肠癌(CRC)高度相关，可迅速诱导依赖IL-17的小鼠结肠炎和肿瘤发生。在无特定病原体的C57BL/6野生型(WT)和多发性肠道肿瘤(MinApc716+/−)小鼠中，我们发现顺序治疗NTBF株9343，然后是ETBF株86-5443-2-2(86)，可以减少结肠炎和肿瘤的发生。同时接受9343和86治疗的小鼠表现出严重的结肠炎和肿瘤形成。在连续治疗的小鼠中，疾病的严重程度归因于9343菌株的优势和IL-17A的降低，但在9343之前或与9343同时定居的86减轻了9343的抗炎作用。值得注意的是，9343介导的保护不依赖于PSA，因为接受ΔPSA9343序贯治疗的小鼠表现出类似的保护。此外，携带PSA9343的SPF WT和Min小鼠表现出相似的IL-10、IL-17和干扰素-γ反应。用9343治疗86-定植小鼠未能阻断86的发病机制。我们的发现表明，独立于PSA的9343定植可以预防结肠炎86，但一旦结肠炎确定，可能就不是有效的治疗方法。
Polysaccharide A (PSA), an immunogenic capsular component of non-toxigenic Bacteroides fragilis (NTBF) strain NCTC 9343, is reported to promote mucosal immune development and suppress colitis. Contrastingly, enterotoxigenic Bacteroides fragilis (ETBF) is highly associated with inflammatory bowel disease (IBD) and colorectal cancer (CRC), rapidly inducing IL-17-dependent murine colitis and tumorigenesis. In specific-pathogen-free (SPF) C57BL/6 wild type (WT) and multiple intestinal neoplasia (MinApc716+/−) mice, we show that sequential treatment of the NTBF strain, 9343, followed by the ETBF strain, 86–5443-2–2 (86), diminished colitis and tumorigenesis. Mice treated simultaneously with 9343 and 86 exhibited both severe colitis and tumorigenesis. Abrogated disease severity in sequentially treated mice was attributed to 9343 strain dominance and decreased IL-17A, but 86 colonization prior to or simultaneous with 9343 mitigated the anti-inflammatory effect of 9343. Remarkably, 9343-mediated protection was independent of PSA, as sequentially treated mice receiving ΔPSA 9343 exhibited similar protection. Further, SPF WT and Min mice colonized with PSA-competent or PSA-deficient 9343 exhibited similar IL-10, IL-17, and IFN-γ responses. Treatment of 86-colonized mice with 9343 failed to disrupt 86 pathogenesis. Our findings demonstrate 9343 colonization, independent of PSA, offers prophylaxis against colitis-inducing 86 but may not be a valid therapy once colitis is established.
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影响因子：
4
作者：
Hillman, J. D.;Mo, J.;Hillman, C. H.
通讯作者：
Hillman, C. H.
肠道共生型细菌的抗菌蛋白具有宿主免疫蛋白的MACPF结构域。
影响因子：
3.6
作者：
Chatzidaki-Livanis M;Coyne MJ;Comstock LE
通讯作者：
Comstock LE
影响因子：
5
作者：
Gillor O;Etzion A;Riley MA
通讯作者：
Riley MA
影响因子：
--
作者：
Chiu CC;Ching YH;Wang YC;Liu JY;Li YP;Huang YT;Chuang HL
通讯作者：
Chuang HL
影响因子：
56.9
作者：
Li, Simone S.;Zhu, Ana;Bork, Peer
通讯作者：
Bork, Peer