The gut microbiota plays an essential role in host health by regulating gut barrier function and immune system homeostasis. However, research into the physiological and immunological functions of the gut microbiota using In Vitro models that mimic the immune environment of the gut remains limited. Herein, we developed the Gut Microbial Immune & Epithelial Cellular System (GutMICS), a device for coculturing anaerobic gut microbes with host cells, including intestinal epithelial and immune cells. Coculturing Akkermansia muciniphila with GutMICS sustained host cell viability and microbial activity for 72 h. In a lipopolysaccharide- and tumor necrosis factor-α (TNF-α)-induced inflammation model, A. muciniphila enhanced the intestinal barrier function, prevented barrier disruption, reduced pro-inflammatory cytokines (interleukin (IL)-6, TNF-α), and increased anti-inflammatory cytokines (IL-10). Additionally, A. muciniphila protected against Salmonella Typhimurium infection by reducing adhesion and invasion, thereby preventing pathogen-induced cell death. This study used GutMICS to characterize the anti-inflammatory properties of A. muciniphila and its ability to inhibit pathogen infection, demonstrating that GutMICS is a valuable tool for assessing the effects of anaerobic gut microbes on host cells. The ability of the system to simulate various inflammatory environments is expected to have broad applications in the study of host-microbe interactions.