Lemon Exosome-like Nanoparticles-Manipulated Probiotics Protect Mice from C. d iff Infection

Chao Lei; Jingyao Mu; Yun Teng; Liqing He; Fangyi Xu; Xiangcheng Zhang; Kumaran Sundaram; Anil Kumar; Mukesh K Sriwastva; Matthew B Lawrenz; Lifeng Zhang; Jun Yan; Wenke Feng; Craig J McClain; Xiang Zhang; Huang-Ge Zhang

doi:10.1016/j.isci.2020.101571

Lemon Exosome-like Nanoparticles-Manipulated Probiotics Protect Mice from C. d iff Infection

iScience. 2020 Sep 16;23(10):101571. doi: 10.1016/j.isci.2020.101571. eCollection 2020 Oct 23.

Authors

Chao Lei¹, Jingyao Mu¹, Yun Teng¹, Liqing He², Fangyi Xu¹, Xiangcheng Zhang³, Kumaran Sundaram¹, Anil Kumar¹, Mukesh K Sriwastva¹, Matthew B Lawrenz^{4

5}, Lifeng Zhang¹, Jun Yan¹, Wenke Feng⁶, Craig J McClain⁶, Xiang Zhang², Huang-Ge Zhang^{7

1

4}

Affiliations

¹ Department of Chemistry, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA.
² Kidney Disease Program and Clinical Proteomics Center, University of Louisville, Louisville, KY, USA.
³ Department of ICU, the Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu 223300, China.
⁴ Department of Microbiology & Immunology, University of Louisville, Louisville, KY 40202, USA.
⁵ Center for Predictive Medicine, University of Louisville, Louisville, KY 40202, USA.
⁶ Department of Medicine, University of Louisville, Louisville, KY 40202, USA.
⁷ Robley Rex Veterans Affairs Medical Center, Louisville, KY 40206, USA.

Abstract

Clostridioides difficile (C. diff) is the leading cause of antibiotic-associated colitis. Here, we report that lemon exosome-like nanoparticles (LELNs) manipulated probiotics to inhibit C. diff infection (CDI). LELN-manipulated Lactobacillus rhamnosus GG (LGG) and Streptococcus thermophilus ST-21 (STH) (LELN-LS) decrease CDI mortality via an LELN-mediated increase in bile resistance and gut survivability. LELN-LS treatment increases the AhR ligands indole-3-lactic acid (I3LA) and indole-3-carboxaldehyde (I3Ald), leading to induction of IL-22, and increases lactic acid leading to a decrease of C. diff fecal shedding by inhibiting C. diff growth and indole biosynthesis. A synergistic effect between STH and LGG was identified. The STH metabolites inhibit gluconeogenesis of LGG and allow fructose-1,6-bisphosphate (FBP) to accumulate in LGG; accumulated FBP then activates lactate dehydrogenase of LGG (LGG-LDH) and enhances production of lactic acid and the AhR ligand. Our findings provide a new strategy for CDI prevention and treatment with a new type of prebiotics.

Keywords: Dairy Microbiology; Microbial Metabolism; Nanoparticles.

Abstract

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