Work

Harnessing flavonoids to control probiotic function: in situ application of a naringenin-responsive genetic circuit

Year: 2025

Type: article

Abstract: ABSTRACT Efforts to improve probiotics’ capabilities through synthetic biology have recently increased. Using naturally occurring plant-based compounds, such as flavonoids, as inputs of genetic circuits introduced in probiotics is a promising strategy to enhance or introduce a beneficial phenotype to the host. However, flavonoid-responsive genetic circuits have not yet been applied in host-microbe conditions. In this work, we have characterized the FdeR-based naringenin-responsive genetic circuit in the probiotic (Escherichia coli Nissle 1917) (EcN), both in vitro and in situ , applying the FdeR system in EcN colonizing mice guts. In culture, the circuit demonstrated a 131-fold activation upon naringenin exposure. In mice, circuit activity was monitored via luminescence produced by Nanoluc in fecal samples following oral gavage of naringenin (100 mg/kg), resulting in a 34-fold luminescence increase. This activation decreased over 24 hours but was reinduced after a second gavage with naringenin. These findings demonstrate the potential of naringenin-responsive genetic circuits to program probiotic phenotypes in vivo through external compound administration. Future studies should evaluate lower naringenin dosages and naringenin-rich foods as alternative inputs. IMPORTANCE Engineering probiotics is a rapidly advancing field in synthetic biology. Genetic circuits, which enable precise and predictable control of microbial phenotypes, are central to this effort. Leveraging natural, plant-based compounds like flavonoids to control gene expression offers a promising strategy for developing next-generation probiotics with enhanced capabilities. This study demonstrates the activity of a flavonoid-responsive genetic circuit during host-microbe interactions. The findings provide a foundation for using beneficial compounds like naringenin as inputs to drive desired phenotypes in vivo . In addition, this work expands the range of genetic circuit inputs, facilitating the design of more sophisticated, multi-input systems for probiotic engineering.

Source: Microbiology Spectrum

DOI: 10.1128/spectrum.02890-24

Authors: Brenno Wendler Miranda, Lucas Henrique Junges, Emanuel Maltempi de Souza, Paula Santana Lunardi, Marcelo Müller-Santos

Institution: Universidade Federal do Paraná

Language: English

Topic: Bacterial Genetics and Biotechnology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDGs: Zero hunger, Good health and well-being

Open Access status: gold

Estimated APC paid: $2,500