Cell adhesion proteins play a crucial role in ensuring the barrier function of the intestinal epithelium by forming intercellular tight junctions that prevent the invasion of harmful substances, microorganisms, and toxins into the organism’s internal environment. However, the comprehensive impact of SCFA-M on the modulation of these proteins and their connection with the microbiome of the duodenal intestine of broiler chickens has been overlooked by researchers, thus emphasizing the significance of these studies. The research was carried out on Cobb 500 broiler chickens in conditions of industrial poultry farming. The experimental group chickens were administered with SCFA-M in drinking water (1% solution of C-3 C-10). The results of the experiment revealed that the administration of SCFA-M to chickens was characterized by increased expression of E-cadherin, fibronectin, IFN-α, and decreased expression of IFN-γ in the duodenum of broiler. Specifically, SCFA-M administration to chickens was associated with an increase in the expression level of E-cadherin in the duodenal intestine by 25.8–30.4% (P≤0.001), fibronectin by 17.8–37.0% (P≤0.001), IFN-α by 21.0–71.6% (P≤0.001), and a decrease in the expression of IFN-γ by 13.5%–49.9% (P≤0.01–0.001) compared to the control group chickens. The correlations of molecular marker expression (E-cadherin, fibronectin, IFN-α, and IIFN-γ) in the duodenum of broiler chickens significantly varied throughout the technological cycle not only in magnitude but also in its trend. Obtained results demonstrated that the marker content was positively correlated with Escherichia coli content (r = 0.79–0.87) in 22-day-old broiler chickens. Contrary, marker content was negatively correlated with E. coli content (r = –0.84…–0.68), Staphylococcus spp. and Enterococcus spp. (r = 0.23–0.91) in 29-day-old chickens. Furthermore, this index was negatively correlated with Staphylococcus spp. content (r = –0.83…–0.51) in 45-day-old chickens. The exposure to SCFA-M induced the changes which associated with strong direct correlations of E-cadherin, fibronectin, IFN-α, and IFN-γ with Staphylococcus spp. content in the duodenum of 22-day-old broiler chickens (r = 0.81–0.91). Molecular markers content exhibited strong inverse correlation links with E. coli content in 36-day-old broiler chickens (r = –0.92…–0.80). Thus, the application of SCFA-M induced the beneficial effect on the modulation of molecular marker expression (E- cadherin, fibronectin, IFN-α, and IFN-γ) in the duodenum. The further research required to construct the optimized protocols for SCFA-M applying in poultry farming, which would replace or minimize the use of antibacterial drugs.