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

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

doi:10.1038/s41467-018-07359-8

Claudia Burrello, Simone Guglielmetti + Show 14 more

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https://doi.org/10.1038/s41467-018-07359-8

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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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Alteration of the gut microbiota has been associated with different gastrointestinal disorders
Given the strict interdependence between intestinal immune system and the host microbiota[45], we aimed to explore immune pathways selectively modulated by Faecal microbiota transplantation (FMT), We asked if therapeutic FMT administration in colitic mice induced variations in the frequencies and in the functional activities of the immune cell colonic infiltrate
We evaluated if FMT administration might influence specific immune cells functional activities that are directly correlated to bacterial antigens presentation

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Introduction

Alteration of the gut microbiota has been associated with different gastrointestinal disorders. We show that therapeutic FMT reduces colonic inflammation and initiates the restoration of intestinal homeostasis through the simultaneous activation of different immune-mediated pathways, 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 MHCIIdependent 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. Other host’s cellular components contribute to homeostasis maintenance through the secretion of antimicrobial peptides (AMPs)[12]

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