Therapeutic faecal microbiota transplantation controls intestinal inflammation through IL10 secretion by immune cells

被引:292
作者
Burrello, Claudia [1 ,2 ]
Garavaglia, Federica [1 ]
Cribiu, Fulvia Milena [3 ]
Ercoli, Giulia [3 ]
Lopez, Gianluca [3 ]
Troisi, Jacopo [4 ,5 ,6 ]
Colucci, Angelo [4 ,5 ]
Guglietta, Silvia [1 ]
Carloni, Sara [7 ]
Guglielmetti, Simone [8 ]
Taverniti, Valentina [8 ]
Nizzoli, Giulia [9 ]
Bosari, Silvano [3 ]
Caprioli, Flavio [9 ,10 ]
Rescigno, Maria [7 ]
Facciotti, Federica [1 ]
机构
[1] European Inst Oncol IRCCS, Dept Expt Oncol, Via Adamello 16, I-20139 Milan, Italy
[2] Univ Milan, Dept Oncol & Hematooncol, Via F Sforza 28, I-20122 Milan, Italy
[3] Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Pathol Unit, Via F Sforza 35, I-20135 Milan, Italy
[4] Univ Salerno, Dept Med Surg & Dent, Scuola Med Salernitana, I-84081 Baronissi, SA, Italy
[5] Univ Salerno, Theoreo Srl, Spin Off Co, Via Ulivi 3, I-84090 Montecorvino Pugliano, SA, Italy
[6] EBRIS, Via S de Renzi 3, I-84125 Salerno, SA, Italy
[7] Humanitas Clin & Res Ctr, Lab Mucosal Immunol & Microbiota, Via Manzoni 56, I-20089 Milan, Italy
[8] Univ Milan, Dept Food Environm & Nutr Sci DeFENS, Via Celoria 2, I-20133 Milan, Italy
[9] Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Gastroenterol & Endoscopy Unit, Via F Sforza 35, I-20135 Milan, Italy
[10] Univ Milan, Dept Pathophysiol & Transplantat, Via F Sforza 28, I-20135 Milan, Italy
关键词
ACTIVE ULCERATIVE-COLITIS; KILLER T-CELLS; BOWEL-DISEASE; GUT MICROBIOME; T(H)17 CELLS; BACTERIA; HOMEOSTASIS; METABOLITES; EXPRESSION; RECEPTOR;
D O I
10.1038/s41467-018-07359-8
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Alteration of the gut microbiota has been associated with different gastrointestinal disorders. Normobiosis restoration by faecal microbiota transplantation (FMT) is considered a promising therapeutic approach, even if the mechanisms underlying its efficacy are at present largely unknown. Here we sought to elucidate the functional effects of therapeutic FMT administration during experimental colitis on innate and adaptive immune responses in the intestinal mucosa. We show that therapeutic FMT reduces colonic inflammation and initiates the restoration of intestinal homeostasis through the simultaneous activation of different immune-mediated pathways, ultimately leading to IL-10 production by innate and adaptive immune cells, including CD4(+) T cells, iNKT cells and Antigen Presenting Cells (APC), and reduces the ability of dendritic cells, monocytes and macrophages to present MHCII-dependent bacterial antigens to colonic T cells. These results demonstrate the capability of FMT to therapeutically control intestinal experimental colitis and poses FMT as a valuable therapeutic option in immune-related pathologies.
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页数:17
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