treatment of murine colitis by saccharomyces boulardii secreting atrial natriuretic peptide

Inflammatory bowel disease is a lifelong disorder that involves chronic inflammation in the small and large intestines. current therapies, including aminosalicylates, corticosteroids, and anti-inflammatory biologics, can only alleviate the symptoms and often cause adverse effects with long-term usage. engineered probiotics provide an alternative approach to treat inflammatory bowel disease in a self-renewable and local delivery fashion. in this work, we utilized a yeast probiotic saccharomyces boulardii for this purpose. we developed a robust method to integrate recombinant genes into the ty elements of s. boulardii. stable yeast cell lines that secreted various anti-inflammatory proteins, including il-10, tnfr1-ecd, alkaline phosphatase, and atrial natriuretic peptide (anp), were successfully created and investigated for their efficacies to the dss-induced colitis in mice through oral administration. while il-10, tnfr1-ecd, and alkaline phosphatase did not show therapeutic effects, the anp-secreting s. boulardii effectively ameliorated the mouse conditions as reflected by the improvements in body weight, disease activity index, and survival rate. a post-mortem examination revealed that the anp-treated mice exhibited significant downregulations of tnf-α and il-1β and an upregulation of il-6 in colon tissues. this observation is consistent with the previous reports showing that tnf-α and il-1β are responsible for initiating the pathogenesis, whereas il-6 plays a protective role in colitis. overall, we demonstrated that s. boulardii is a safe and robust vehicle for recombinant protein delivery in the gastrointestinal tract, and anp is a potential anti-inflammatory drug for colitis treatment.