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.
In women with endometriosis, the lifetime risk of ovarian cancer is increased from 1.4% to about 1.9%. The risk of clear cell and endometrioid ovarian cancer is, respectively, tripled and doubled. Atypical endometriosis, observed in 1-3% of endometriomas excised in premenopausal women, is the intermediate precursor lesion linking typical endometriosis and clear cell/endometrioid tumors. Prolonged oral contraceptive use is associated with a major reduction in ovarian cancer risk among women with endometriosis. Surveillance ± progestogen treatment or surgery should be discussed in perimenopausal women with small, typical endometriomas. In most perimenopausal women with a history of endometriosis but without endometriomas, surveillance instead of risk-reducing bilateral salpingo-oophorectomy seems advisable. Risk-reducing salpingo-oophorectomy might benefit patients at particularly increased risk, but the evidence is inconclusive. Risk profiling models and decision aids may assist patients in their choice. Screening of the general perimenopausal population to detect asymptomatic endometriomas is unlikely to reduce disease-specific mortality.
Different gastrointestinal disorders, including inflammatory bowel diseases (IBD), have been linked to alterations of the gut microbiota composition, namely dysbiosis. Fecal microbiota transplantation (FMT) is considered an encouraging therapeutic approach for ulcerative colitis patients, mostly as a consequence of normobiosis restoration. We recently showed that therapeutic effects of FMT during acute experimental colitis are linked to functional modulation of the mucosal immune system and of the gut microbiota composition. Here we analysed the effects of therapeutic FMT administration during chronic experimental colitis, a condition more similar to that of IBD patients, on immune-mediated mucosal inflammatory pathways. Mucus and feces from normobiotic donors were orally administered to mice with established chronic Dextran Sodium Sulphate (DSS)-induced colitis. Immunophenotypes and functions of infiltrating colonic immune cells were evaluated by cytofluorimetric analysis. Compositional differences in the intestinal microbiome were analyzed by 16S rRNA sequencing. Therapeutic FMT in mice undergoing chronic intestinal inflammation was capable to decrease colonic inflammation by modulating the expression of pro-inflammatory genes, antimicrobial peptides, and mucins. Innate and adaptive mucosal immune cells manifested a reduced pro-inflammatory profile in FMT-treated mice. Finally, restoration of a normobiotic core ecology contributed to the resolution of inflammation. Thus, FMT is capable of controlling chronic intestinal experimental colitis by inducing a concerted activation of anti-inflammatory immune pathways, mechanistically supporting the positive results of FMT treatment reported in ulcerative colitis patients.
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