AbstractThe current study was conducted to evaluate the effects of a yeast cell wall product (YCWP) on the performance, the population of Lactobacillusand coliform bacteria and PGC-1α, TLR4, IL-10and PPARγgenes expression in the intestine of broilers. Dietary treatments were as follows: basal diet (control), control diet + 0.3 g/kg colistin or 0.15, 0.3, 0.45 and 0.6 g/kg YCWP. Feed intake and feed conversion ratio were lower in the YCWP-fed birds compared to the control. Colistin and YCWP fed birds had higher Lactobacillusand lower coliform bacteria counts than control birds (p < .05). Total and IgM antibody against sheep red blood cells was linearly increased by adding the YCWP to the diet (p < .05). Adding the YCWP to the diet linearly increased the caecal concentration of propionate (p < .05). Orthogonal and polynomial contrasts showed that the YCWP significantly improved the villus height, crypt depth, villus height: crypt depth, villus width, and villus surface area (p < .05). The lower concentrations of the YCWP (0.15 and 0.30 g/kg) increased the PPARγtranscription (p < .05), while its upper concentration (0.45 and 0.6 g/kg of diet) did not change the PPARγgene expression. PGC-1αtranscription was increased with 0.15 g/kg of the YCWP supplementation (p < .05). Dietary inclusion of the YCWP decreased the TLR4gene expression (p < .05) and increased the downstream IL-10cytokine (p < .05). In conclusion, YCWP improved the broiler’s performance by modifying the gut microflora. Also, YCWP supplementation had an immune regulatory effect via local and systemic responses involving TLR4, IL-10,and PPARγ.HighlightsAdding YCWP to the broilers diet did not significantly affect body weight gain, but reduced FCR.Adding 0.45 and 0.6 g of YCWP to the diet, increased the Lactobacillusnumber and reduced the coliform bacteria number in the ileum.YCWP supplementation increased the production of antibodies (total, IgG, and IgM) against SRBC and developed lymphatic organs.Adding 0.6 g of YCWP to the diet increased villus height and villus surface area and reduced the crypt depth.YCWP supplement had an immune regulatory effect via local and systemic responses involving TLR4,IL-10, and PPARγ.