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

Claudia Burrello, Federica Garavaglia, Fulvia Milena Cribiù, Giulia Ercoli, Gianluca Lopez, Jacopo Troisi, Angelo Colucci, Silvia Guglietta, Sara Carloni, Simone Guglielmetti, Valentina Taverniti, Giulia Nizzoli, Silvano Bosari, Flavio Caprioli, Maria Rescigno, Federica Facciotti

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

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transplantation
secretions
T-cells
Interleukin-10
Restoration
Inflammation
Bacterial Antigens
Macrophages
Pathology
cells
antigens
Colitis
restoration
Chemical activation
monocytes
T-Lymphocytes
Therapeutics
homeostasis
Natural Killer T-Cells
macrophages

Cite this

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title = "Therapeutic faecal microbiota transplantation controls intestinal inflammation through IL10 secretion by immune cells",
abstract = "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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AU - Burrello, Claudia

AU - Garavaglia, Federica

AU - Cribiù, Fulvia Milena

AU - Ercoli, Giulia

AU - Lopez, Gianluca

AU - Troisi, Jacopo

AU - Colucci, Angelo

AU - Guglietta, Silvia

AU - Carloni, Sara

AU - Guglielmetti, Simone

AU - Taverniti, Valentina

AU - Nizzoli, Giulia

AU - Bosari, Silvano

AU - Caprioli, Flavio

AU - Rescigno, Maria

AU - Facciotti, Federica

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N2 - 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.

AB - 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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