The role of genetically modified K. lactis in the treatment of Inflammatory Bowel Disease

Abstract

Abstract Background. Inflammatory bowel disease (IBD) is a chronic inflammatory disorder that mainly includes ulcerative colitis and Crohn's disease, which affect the mucosal barrier and the gastrointestinal tract wall (Vidal-Gallardo et al., 2024). The development of IBD is influenced by complex interplay of genetic factors, gut microbiota, and environmental factors (Matsuoka & Kanai, 2015). Current therapies like glucocorticosteroids and immunosuppressive drugs have a range of side effects and are not effective in all patients, prompting scientists to find alternative treatment methods for IBD (Ben-Horin & Chowers, 2011). One promising strategy is the use of genetically modified microbes. K. lactis is a potential candidate due to its probiotic properties and ability to produce recombinant protein (Spohner et al., 2016). Since CCR5 expression is increased in IBD, targeting the CCL5-CCR5 may help reduce inflammation (Ye et al.) (Abdirassil et al., 2025; Mencarelli et al.). Objective. This research aims to investigate the role of genetically modified yeast K. lactis, targeting CCR5 to neutralize the CCL5-CCR5 inflammatory axis in the treatment of IBD. Methods. We divided mice into two groups: control and group treated with genetically modified K. lactis and wild-type K. lactis. I induced acute IBD with TNBS intrarectal. On the next stage, mice monitored for clinical manifestation of the disease: weight loss, stool consistency, rectal bleeding, and activity. After 5 days, mice were sacrificed, and their colon was dissected for slide preparation. In the following stage, an immunofluorescence microscope detected inflammatory markers, using specific antibodies such as anti- IL-17A and anti-MMP-9 in tissues with K. lactis treatment and without. Conclusion. Our results suggest that engineered K. lactis may influence mucosal immune signaling. Increased IL-17A expression in treatment groups may indicate activation of compensatory or alternative inflammatory pathways. The MMP-9 expression was not detected under our experimental conditions. Although the treatment did not significantly improve clinical or microscopic signs of colitis, the findings that genetically modified yeast may act as therapeutic vector capable of influencing inflammatory pathways in IBD.