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.

Promising Treatment for Type 2 Diabetes: Fecal Microbiota Transplantation Reverses Insulin Resistance and Impaired Islets

“…Studies have shown that FMT is involved in the low-grade inflammation characterized by metabolic disorders. It has been reported that therapeutic FMT could decrease the secretion of inflammatory factors and triggered several immune-mediated signal-pathways in colitis (Burrello et al, 2018). As mentioned in another study, transplantation of gut microbiota like F. prausnitzii prevented the inflammation damage in the pancreas (Ganesan et al, 2018).…”

“…In our study, we established T2DM animal models by feeding mice high-fat diet combined with streptozotocin and observed that FMT treatment successfully reduced FBG and improved glucose tolerance on diabetic mice (Figures 1A,B). It was possible to restore the balance of intestinal microflora to promote host homeostasis (Burrello et al, 2018). According to a recent study, in metabolic syndrome, when commensal bacteria from various phyla stay in a certain range, they contribute to control the ratio of pathogenic species and support optimal physical conditions (Burrello et al, 2018).…”

“…It was possible to restore the balance of intestinal microflora to promote host homeostasis (Burrello et al, 2018). According to a recent study, in metabolic syndrome, when commensal bacteria from various phyla stay in a certain range, they contribute to control the ratio of pathogenic species and support optimal physical conditions (Burrello et al, 2018). Glycated hemoglobin test usually reflects the patient's blood glucose control in the last 8-10 weeks and our ELISA results of HbA1c further provided evidence of the hypoglycemic effect of FMT ( Figure 1C).…”

Considering the Immune System during Fecal Microbiota Transplantation for Clostridioides difficile Infection

“…Recently, experimental evidence has linked the effectiveness of FMT for colitis with immunosuppression. FMT therapeutically controlled gut inflammation and colitis via the induction of IL-10 and TGF-β, cytokines critical for Treg cell accumulation in the intestine [67,68]. Whether FMT-directed immunosuppression aids in the recovery from C. difficile requires further investigation.…”

The microbiota and immune‐mediated diseases: Opportunities for therapeutic intervention

“…While the mechanism has not been established in humans, it is likely to involve microbial activation of innate immune responses through pattern recognition receptors on macrophages and DCs, leading to activation of pathogenic Th1/Th17 cells. Studies in the DSS‐induced murine colitis model have shown that therapeutic FMT promotes IL‐10‐dependent suppression of APC and CD4 T cells that mediate colon inflammation [60]. Therefore, FMT in humans may also function through introduction of bacteria to the gut that promote regulatory immune responses, which suppress colon inflammation mediated by innate immune cells and T cells.…”