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The health benefits of honey as an oral therapeutic agent for the treatment of diarrhoea caused by Shigella sonnei depend on the ability of honey to withstand human gastrointestinal conditions. This study aimed to investigate whether honey could withstand and inhibit the growth of Shigella sonnei under such conditions. We initially evaluated the survival of Shigella sonnei in human simulated gastric conditions (SGC) and simulated intestinal conditions (SIC). This was followed by determination of the susceptibility of Shigella sonnei to Manuka and Talah honey under gastrointestinal conditions. The colony forming units (CFU) of Shigella sonnei and minimum inhibitory concentrations (MICs) of honey were calculated. Shigella sonnei was unable to survive in the acidic environment of the stomach without food matrix and survived only when inoculated with a food source, resulting in 1.5 × 105 ± 0.2 CFU at 60 min and 1.7 × 105 ± 0.3 CFU after 120 min of incubation. In SIC, it survived both with and without food matrix at the same CFU (1.2 × 107 ±0.4) at 60 min and 1.7 × 107 ±0.2 CFU after 120 min of incubation. Growth of Shigella sonnei was not observed in SGC in the presence of either honey at different concentrations without a food source. In the presence of a food source, Manuka honey inhibited the growth of Shigella sonnei at 10% v/v and Talah honey at 20% v/v dilutions in SGC. In SIC, Manuka honey inhibited the growth of Shigella sonnei at 15% and 20% v/v dilutions, whereas Talah honey inhibited Shigella sonnei at 20% and 25% v/v dilutions without and with food sources, respectively. Shigella sonnei can survive in the acidic environment of the stomach if inoculated with a food source. Acidic pH and pepsin had no deleterious effects on the antibacterial capability of honey. However, bile reduced the antibacterial activity of honey in the intestinal environment. • Shigella sonnei was able to survive in the acidic environment of the stomach when inoculated on ground beef. • Both Manuka and Talah honeys inhibited the growth of Shigella sonnei in the gastrointestinal environment. • Antibacterial activity of honey has increased in gastric simulated conditions. • Bile salts and food reduced the antibacterial activity of honey in intestinal simulated environment. [ABSTRACT FROM AUTHOR]