Genetically Modified Escherichia coli Nissle 1917 Producing Anti-TNF-α Nanobody as a Novel Single-Strain Live Biotherapeutic for Treating Inflammatory Bowel Disease

1

Escherichia coli Nissle 1917 was engineered to secrete the anti-TNF-α nanobody MT1, creating the single-strain platform EcN-MT1.
2

The α-hemolysin signal peptide achieved the highest secretion level of MT1 at 4.6 mg/L, outperforming genomic integrants.
3

EcN-MT1 demonstrated significant therapeutic efficacy in a DSS-induced murine colitis model, improving weight loss and disease activity index.
4

Histopathological analysis showed that EcN-MT1 reduced mucosal ulceration and immune cell infiltration while downregulating pro-inflammatory cytokines.
5

EcN-MT1 treatment restored gut microbial diversity and enriched beneficial taxa associated with anti-inflammatory effects.

Frontiers In Immunology

by Qiumei Zhu, Shitao Feng, Zhende Yan, Zijian Wang, Xinran Huang, Changning Sun, Bingqiang Zhang, Xinrui Li, Yuchao Gu
July 2, 2026

1