Chronic leg ulcers are a major health burden globally, increasing in incidence with ageing and morbidity from diabetes. A common mechanism highlighted in chronic hard to heal wounds is exaggerated and sustained inflammation which inhibits the closure and therefore represents a therapeutic target. In the present study, we analyzed the effect of supernatant extracted from two strains of Faecalibacterium prausnitzii, a commensal gut microbiome known to have anti-inflammatory activity. C57BL/6 wild type mice were subjected to full thickness excisional wounds and randomized for treatment by extracts from SPA2 or SPAH strains versus vehicle control. Four days post wounding there was a dramatic and significant reduction of nuclear p65 staining in wounds reflecting inhibition of NFkB activation. This was accompanied by a decline in proinflammatory cytokines, il12p35 or tnfa. Although the bacterial supernatants did not significantly affect the myeloid immune infiltrate, wound closure was significantly accelerated, as well as collagen and myofibroblast-related gene expression. To further understand the specificity of this effect on NFkB signalling we used pharmacological inhibitor of IKK and NFkB activation versus an inhibitor of the inflammasome (NLRP3). NFkB inhibition resulted in similar acceleration of wound closure however inhibition of the inflammasome did not affect closure. In conclusion, supernatant from specific strains derived from F. prausnitzii can regulate wound inflammation through the NFkB pathway and accelerate wound closure through increased myofibroblast differentiation and collagen deposition. This finding might open new therapeutic avenues for chronic hyperinflammatory diabetic or venous ulcers.