AIEC infection triggers modification of gut microbiota composition in genetically predisposed mice, contributing to intestinal inflammation.
AIEC infection triggers modification of gut microbiota composition in genetically predisposed mice, contributing to intestinal inflammation.
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DOI：
10.1038/s41598-018-30055-y
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发表时间：
2018-08-17
影响因子：
4.6
通讯作者：
Nguyen HTT
中科院分区：
文献类型：
--
作者：
Bretin A;Lucas C;Larabi A;Dalmasso G;Billard E;Barnich N;Bonnet R;Nguyen HTT
在克罗恩病患者的肠黏膜中，黏附侵袭性大肠杆菌（AIEC）的高发率已被证实。AIEC定植于肠道并在遗传易感小鼠模型中诱导炎症，包括CEABAC10转基因（Tg）小鼠，表达人ceacam6 - AIEC受体，以及在AIEC感染反应中表现自噬缺陷的eif2ak4 - / -小鼠。在这里，我们的目的是研究肠道微生物群的改变是否有助于这些小鼠模型中aiec诱导的肠道炎症。为此，eif2ak4基因失活（Tg/eif2ak4−/−）或未失活（Tg/eif2ak4+/+）的eif2ak4+/+和eif2ak4−/−小鼠或CEABAC10 Tg小鼠分别感染AIEC参考菌株LF82或非致病性大肠杆菌K12 MG1655菌株。在所有小鼠组中，LF82比MG1655在肠道中的定殖更好、时间更长。感染前、感染后第1天和第4天，eif2ak4+/+和eif2ak4−/−小鼠的粪便微生物群组成没有差异。与其他组相比，lf82感染的eif2ak4 - / -小鼠在感染后第14天和第21天的粪便微生物群组成发生了改变，感染后第21天的粪便脂钙素-2水平升高，表明肠道微生物群改变后发生了炎症。在lf82感染的Tg/eif2ak4−/−小鼠中也得到了类似的结果。这些结果表明，在遗传易感的宿主中，AIEC定植可能通过改变肠道菌群组成来诱导慢性肠道炎症。
A high prevalence of adherent-invasive E. coli (AIEC) in the intestinal mucosa of Crohn’s disease patients has been shown. AIEC colonize the intestine and induce inflammation in genetically predisposed mouse models including CEABAC10 transgenic (Tg) mice expressing human CEACAM6-receptor for AIEC and eif2ak4−/− mice exhibiting autophagy defect in response to AIEC infection. Here, we aimed at investigating whether gut microbiota modification contributes to AIEC-induced intestinal inflammation in these mouse models. For this, eif2ak4+/+ and eif2ak4−/− mice or CEABAC10 Tg mice invalidated for Eif2ak4 gene (Tg/eif2ak4−/−) or not (Tg/eif2ak4+/+) were infected with the AIEC reference strain LF82 or the non-pathogenic E. coli K12 MG1655 strain. In all mouse groups, LF82 colonized the gut better and longer than MG1655. No difference in fecal microbiota composition was observed in eif2ak4+/+ and eif2ak4−/− mice before infection and at day 1 and 4 post-infection. LF82-infected eif2ak4−/− mice exhibited altered fecal microbiota composition at day 14 and 21 post-infection and increased fecal lipocalin-2 level at day 21 post-infection compared to other groups, indicating that intestinal inflammation developed after microbiota modification. Similar results were obtained for LF82-infected Tg/eif2ak4−/− mice. These results suggest that in genetically predisposed hosts, AIEC colonization might induce chronic intestinal inflammation by altering the gut microbiota composition.
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影响因子：
3.7
作者：
Chassaing B;Srinivasan G;Delgado MA;Young AN;Gewirtz AT;Vijay-Kumar M
通讯作者：
Vijay-Kumar M
影响因子：
30.8
作者：
Kugathasan, Subra;Baldassano, Robert N.;Bradfield, Jonathan P.;Sleiman, Patrick M. A.;Imielinski, Marcin;Guthery, Stephen L.;Cucchiara, Salvatore;Kim, Cecilia E.;Frackelton, Edward C.;Annaiah, Kiran;Glessner, Joseph T.;Santa, Erin;Willson, Tara;Eckert, Andrew W.;Bonkowski, Erin;Shaner, Julie L.;Smith, Ryan M.;Otieno, F. George;Peterson, Nicholas;Abrams, Debra J.;Chiavacci, Rosetta M.;Grundmeier, Robert;Mamula, Petar;Tomer, Gitit;Piccoli, David A.;Monos, Dimitri S.;Annese, Vito;Denson, Lee A.;Grant, Struan F. A.;Hakonarson, Hakon
通讯作者：
Hakonarson, Hakon
影响因子：
3.4
作者：
Lapaquette, Pierre;Bringer, Marie-Agnes;Darfeuille-Michaud, Arlette
通讯作者：
Darfeuille-Michaud, Arlette
影响因子：
16
作者：
Harding, HP;Novoa, I;Ron, D
通讯作者：
Ron, D
影响因子：
56.9
作者：
Gill, Steven R.;Pop, Mihai;Nelson, Karen E.
通讯作者：
Nelson, Karen E.