Engineered Bacteria EcN-MT Alleviate Liver Injury in Cadmium-Exposed Mice via its Probiotics Characteristics and Expressing of Metallothionein

Changwei Zou; Ying Chen; Hongyu Li; Wenyu Li; Jin Wei; Ziyan Li; Xinliang Wang; Tingtao Chen; Hong Huang

doi:10.3389/fphar.2022.857869

Engineered Bacteria EcN-MT Alleviate Liver Injury in Cadmium-Exposed Mice via its Probiotics Characteristics and Expressing of Metallothionein

Front Pharmacol. 2022 Feb 24:13:857869. doi: 10.3389/fphar.2022.857869. eCollection 2022.

Authors

Changwei Zou¹, Ying Chen¹, Hongyu Li², Wenyu Li², Jin Wei³, Ziyan Li¹, Xinliang Wang¹, Tingtao Chen³, Hong Huang¹

Affiliations

¹ Key Laboratory of Poyang Lake Environment and Resource Utilization, School of Resources Environmental and Chemical Engineering, Ministry of Education, Nanchang University, Nanchang, China.
² Queen Mary School, Nanchang University, Nanchang, China.
³ National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China.

Abstract

Cadmium (Cd) exposure is a widespread problem in many parts of the world, but effective means to treat Cd exposure is still lacking. Hence, an engineered strain expressing metallothionein (MT) named Escherichia coli Nissle 1917 (EcN)-MT was constructed, and its potential in the treatment of Cd exposure was evaluated. The in vitro studies showed that metallothionein expressed by EcN-MT could significantly bind Cd. Further, the in vivo results indicated that EcN-MT strain could reduce 26.3% Cd in the liver and increase 24.7% Cd in the feces, which greatly decreased malondialdehyde (MDA) levels and increased catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD) levels in liver, and reduced the expression of toll-like receptor4 (TLR4), nuclear factor-κB (NF-κB), the myeloid differentiation factor 88 (Myd88) andincreased B-cell lymphoma 2 (Bcl-2)/Bcl-2-Associated X (Bax). Moreover, high throughput sequencing results indicated that EcN-MT strain greatly enhanced the beneficial bacteria of Ruminococcaceae, Lactobacillaceae, Akkermansia, Muribaculaceae, Lachnospiraceae, Dubosiella and restored the disturbed microbial ecology to the normal level. Therefore, the high Cd binding capacity of the expressed metallothionein, together with the beneficial characteristics of the host bacteria EcN, makes EcN-MT a sound reagent for the treatment of subchronic Cd exposure-induced liver injury.

Keywords: EcN-MT; cadmium; inflammation; intestinal microbiota; metallothionein; oxidative stress.