Lemon Exosome-like Nanoparticles-Manipulated Probiotics Protect Mice from C. diff 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

iScience (Oct 2020)

Lemon Exosome-like Nanoparticles-Manipulated Probiotics Protect Mice from C. diff 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

Affiliations

Chao Lei: Department of Chemistry, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA
Jingyao Mu: Department of Chemistry, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA
Yun Teng: Department of Chemistry, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA
Liqing He: Kidney Disease Program and Clinical Proteomics Center, University of Louisville, Louisville, KY, USA
Fangyi Xu: Department of Chemistry, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA
Xiangcheng Zhang: Department of ICU, the Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu 223300, China
Kumaran Sundaram: Department of Chemistry, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA
Anil Kumar: Department of Chemistry, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA
Mukesh K. Sriwastva: Department of Chemistry, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA
Matthew B. Lawrenz: Department of Microbiology & Immunology, University of Louisville, Louisville, KY 40202, USA; Center for Predictive Medicine, University of Louisville, Louisville, KY 40202, USA
Lifeng Zhang: Department of Chemistry, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA
Jun Yan: Department of Chemistry, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA
Wenke Feng: Department of Medicine, University of Louisville, Louisville, KY 40202, USA
Craig J. McClain: Department of Medicine, University of Louisville, Louisville, KY 40202, USA
Xiang Zhang: Kidney Disease Program and Clinical Proteomics Center, University of Louisville, Louisville, KY, USA
Huang-Ge Zhang: Robley Rex Veterans Affairs Medical Center, Louisville, KY 40206, USA; Department of Chemistry, University of Louisville, CTRB 309 505 Hancock Street, Louisville, KY 40202, USA; Department of Microbiology & Immunology, University of Louisville, Louisville, KY 40202, USA; Corresponding author

Journal volume & issue: Vol. 23, no. 10
p. 101571

Abstract

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Summary: 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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