The Next-Generation Probiotic -pSK18a-MT Ameliorates Cadmium-Induced Liver Injury by Surface Display of Metallothionein and Modulation of Gut Microbiota

Overview

Journal Nutrients

Date 2024 May 25

PMID 38794706

Authors

Yan Zhang

Hong Huang

Chuanlin Luo

Xinfeng Zhang

Yanjing Chen

Fenfang Yue

Bingqing Xie

Tingtao Chen

Changwei Zou

Affiliations

Soon will be listed here.

Abstract

Cadmium (Cd) is recognized as being linked to several liver diseases. Currently, due to the limited spectrum of drugs available for the treatment of Cd intoxication, developing and designing antidotes with superior detoxification capacity and revealing their underlying mechanisms remains a major challenge. Therefore, we developed the first next-generation probiotic -pSK18a-MT that delivers metallothionein (MT) to overcome Cd-induced liver injury in C57BL/6 mice by utilizing bacterial surface display technology. The results demonstrate that -pSK18a-MT could efficiently express MT without altering the growth and probiotic properties of the strain. Moreover, we found that -pSK18a-MT ameliorated Cd contamination-induced hepatic steatosis, inflammatory cell infiltration, and liver fibrosis by decreasing the expression of aminotransferases along with inflammatory factors. Activation of the Nrf2-Keap1 signaling pathway also further illustrated the hepatoprotective effects of the engineered bacteria. Finally, we showed that -pSK18a-MT improved the colonic barrier function impaired by Cd induction and ameliorated intestinal flora dysbiosis in Cd-poisoned mice by increasing the relative abundance of the Verrucomicrobiota. These data revealed that the combination of and MT both alleviated Cd-induced liver injury to a greater extent and restored the integrity of colonic epithelial tissues and bacterial dysbiosis.

References

Abu-El-Zahab H, Hamza R, Montaser M, El-Mahdi M, Al-Harthi W . Antioxidant, antiapoptotic, antigenotoxic, and hepatic ameliorative effects of L-carnitine and selenium on cadmium-induced hepatotoxicity and alterations in liver cell structure in male mice. Ecotoxicol Environ Saf. 2019; 173:419-428. DOI: 10.1016/j.ecoenv.2019.02.041. View

Hancock V, Dahl M, Klemm P . Probiotic Escherichia coli strain Nissle 1917 outcompetes intestinal pathogens during biofilm formation. J Med Microbiol. 2010; 59(Pt 4):392-399. DOI: 10.1099/jmm.0.008672-0. View

Noor K, Ijaz M, Ehsan N, Tahir A, Yeni D, Zihad S . Hepatoprotective role of vitexin against cadmium-induced liver damage in male rats: A biochemical, inflammatory, apoptotic and histopathological investigation. Biomed Pharmacother. 2022; 150:112934. DOI: 10.1016/j.biopha.2022.112934. View

Sanjeev S, Bidanchi R, Murthy M, Gurusubramanian G, Roy V . Influence of ferulic acid consumption in ameliorating the cadmium-induced liver and renal oxidative damage in rats. Environ Sci Pollut Res Int. 2019; 26(20):20631-20653. DOI: 10.1007/s11356-019-05420-7. View

Rafati Rahimzadeh M, Rafati Rahimzadeh M, Kazemi S, Moghadamnia A . Cadmium toxicity and treatment: An update. Caspian J Intern Med. 2017; 8(3):135-145. PMC: 5596182. DOI: 10.22088/cjim.8.3.135. View

Refaie M, El-Hussieny M, Zenhom N . Protective role of nebivolol in cadmium-induced hepatotoxicity via downregulation of oxidative stress, apoptosis and inflammatory pathways. Environ Toxicol Pharmacol. 2018; 58:212-219. DOI: 10.1016/j.etap.2018.01.011. View

Feng D, Zhang H, Jiang X, Zou J, Li Q, Mai H . Bisphenol A exposure induces gut microbiota dysbiosis and consequent activation of gut-liver axis leading to hepatic steatosis in CD-1 mice. Environ Pollut. 2020; 265(Pt A):114880. DOI: 10.1016/j.envpol.2020.114880. View

Zhang H, Liu X, Elsabagh M, Zhang Y, Ma Y, Jin Y . Effects of the Gut Microbiota and Barrier Function on Melatonin Efficacy in Alleviating Liver Injury. Antioxidants (Basel). 2022; 11(9). PMC: 9495757. DOI: 10.3390/antiox11091727. View

Vicente-Sanchez C, Egido J, Sanchez-Gonzalez P, Perez-Barriocanal F, Lopez-Novoa J, Morales A . Effect of the flavonoid quercetin on cadmium-induced hepatotoxicity. Food Chem Toxicol. 2008; 46(6):2279-87. DOI: 10.1016/j.fct.2008.03.009. View

10.

Liu Y, Kang W, Liu S, Li J, Liu J, Chen X . Gut microbiota-bile acid-intestinal Farnesoid X receptor signaling axis orchestrates cadmium-induced liver injury. Sci Total Environ. 2022; 849:157861. DOI: 10.1016/j.scitotenv.2022.157861. View

11.

Zhou D, Wang X, Xu X, Chen W, Wei J, Chen T . Anti-Tumor Effects of Engineered VNP20009-Abvec-Igκ-mPD-1 Strain in Melanoma Mice via Combining the Oncolytic Therapy and Immunotherapy. Pharmaceutics. 2022; 14(12). PMC: 9781615. DOI: 10.3390/pharmaceutics14122789. View

12.

Yu Z, Wan X, Xiao M, Zheng C, Zhou X . Puerarin induces Nrf2 as a cytoprotective mechanism to prevent cadmium-induced autophagy inhibition and NLRP3 inflammasome activation in AML12 hepatic cells. J Inorg Biochem. 2021; 217:111389. DOI: 10.1016/j.jinorgbio.2021.111389. View

13.

Zhu M, Li H, Bai L, Wang L, Zou X . Histological changes, lipid metabolism, and oxidative and endoplasmic reticulum stress in the liver of laying hens exposed to cadmium concentrations. Poult Sci. 2020; 99(6):3215-3228. PMC: 7597684. DOI: 10.1016/j.psj.2019.12.073. View

14.

Cenit M, Matzaraki V, Tigchelaar E, Zhernakova A . Rapidly expanding knowledge on the role of the gut microbiome in health and disease. Biochim Biophys Acta. 2014; 1842(10):1981-1992. DOI: 10.1016/j.bbadis.2014.05.023. View

15.

Xu Z, Weng Z, Liang J, Liu Q, Zhang X, Xu J . Association between urinary cadmium concentrations and liver function in adolescents. Environ Sci Pollut Res Int. 2022; 29(26):39768-39776. DOI: 10.1007/s11356-022-18950-4. View

16.

Genchi G, Sinicropi M, Lauria G, Carocci A, Catalano A . The Effects of Cadmium Toxicity. Int J Environ Res Public Health. 2020; 17(11). PMC: 7312803. DOI: 10.3390/ijerph17113782. View

17.

Yang Z, He Y, Wang H, Zhang Q . Protective effect of melatonin against chronic cadmium-induced hepatotoxicity by suppressing oxidative stress, inflammation, and apoptosis in mice. Ecotoxicol Environ Saf. 2021; 228:112947. DOI: 10.1016/j.ecoenv.2021.112947. View

18.

Zhang H, Yan J, Xie Y, Chang X, Li J, Ren C . Dual role of cadmium in rat liver: Inducing liver injury and inhibiting the progression of early liver cancer. Toxicol Lett. 2021; 355:62-81. DOI: 10.1016/j.toxlet.2021.11.004. View

19.

Garcia-Nino W, Pedraza-Chaverri J . Protective effect of curcumin against heavy metals-induced liver damage. Food Chem Toxicol. 2014; 69:182-201. DOI: 10.1016/j.fct.2014.04.016. View

20.

Liu C, Zhu Y, Lu Z, Guo W, Tumen B, He Y . Cadmium Induces Acute Liver Injury by Inhibiting Nrf2 and the Role of NF-κB, NLRP3, and MAPKs Signaling Pathway. Int J Environ Res Public Health. 2019; 17(1). PMC: 6981660. DOI: 10.3390/ijerph17010138. View