Dual engineered bacteria improve inflammatory bowel disease in mice

• Published in: Applied microbiology and biotechnology Vol. 108; no. 1; p. 333
• Main Authors: Wu, Yong-Qi, Zou, Zhen-Ping, Zhou, Ying, Ye, Bang-Ce
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2024; Springer Nature B.V
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Applied Microbial and Cell Physiology; Bacteria; Biomedical and Life Sciences; Biotechnology; Coliforms; Colon - microbiology; Colon - pathology; Cytokines - metabolism; Disease Models, Animal; Drugs; E coli; Escherichia coli - genetics; Fibrosis; Gastrointestinal Microbiome; Genetic Engineering; Health services; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - microbiology; Inflammatory Bowel Diseases - therapy; Interleukin-10 - genetics; Intestine; Life Sciences; Mice; Mice, Inbred C57BL; Microbial Genetics and Genomics; Microbiology; Nanobodies; Oral administration; Probiotics; Probiotics - administration & dosage; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Engineered bacteria; Inflammatory bowel disease; Nissle 1917; IL-10; Anti-TNF-α nanobody; E.coli Nissle 1917
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-024-13163-w

Currently, there are many different therapies available for inflammatory bowel disease (IBD), including engineered live bacterial therapeutics. However, most of these studies focus on producing a single therapeutic drug using individual bacteria, which may cause inefficacy. The use of dual drugs can enhance therapeutic effects. However, expressing multiple therapeutic drugs in one bacterial chassis increases the burden on the bacterium and hinders good secretion and expression. Therefore, a dual-bacterial, dual-drug expression system allows for the introduction of two probiotic chassis and enhances both therapeutic and probiotic effects. In this study, we constructed a dual bacterial system to simultaneously neutralize pro-inflammatory factors and enhance the anti-inflammatory pathway. These bacteria for therapy consist of Escherichia coli Nissle 1917 that expressed and secreted anti-TNF-α nanobody and IL-10, respectively. The oral administration of genetically engineered bacteria led to a decrease in inflammatory cell infiltration in colon and a reduction in the levels of pro-inflammatory cytokines. Additionally, the administration of engineered bacteria did not markedly aggravate gut fibrosis and had a moderating effect on intestinal microbes. This system proposes a dual-engineered bacterial drug combination treatment therapy for inflammatory bowel disease, which provides a new approach to intervene and treat IBD. Key points • The paper discusses the effects of using dual engineered bacteria on IBD • Prospects of engineered bacteria in the clinical treatment of IBD Graphical Abstract