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Lactobacillus plantarum ameliorates NASH-related inflammation by upregulating L-arginine production

Authors
 Dong Yun Kim  ;  Jun Yong Park  ;  Heon Yung Gee 
Citation
 EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.55(11) : 2332-2345, 2023-11 
Journal Title
EXPERIMENTAL AND MOLECULAR MEDICINE
ISSN
 1226-3613 
Issue Date
2023-11
MeSH
Animals ; Choline / metabolism ; Diet, High-Fat / adverse effects ; Disease Models, Animal ; Hepatitis* / pathology ; Humans ; Inflammation / metabolism ; Lactobacillus plantarum* / metabolism ; Liver / metabolism ; Methionine ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease* / drug therapy ; Non-alcoholic Fatty Liver Disease* / etiology
Abstract
Lactobacillus is a probiotic with therapeutic potential for several diseases, including liver disease. However, the therapeutic effect of L. plantarum against nonalcoholic steatohepatitis (NASH) and its underlying mechanisms remain unelucidated. Therefore, we delineated the L. plantarum-mediated NASH regulation in a mouse model to understand its therapeutic effect. We used a choline-deficient high-fat diet (CD-HFD)-induced murine model that recapitulated the critical features of human metabolic syndrome and investigated the effect of L. plantarum on NASH pathogenesis using transcriptomic, metagenomic, and immunohistochemistry analyses. Validation experiments were performed using liver organoids and a murine model fed a methionine-choline-deficient (MCD) diet. L. plantarum treatment in mice significantly decreased liver inflammation and improved metabolic phenotypes, such as insulin tolerance and the hepatic lipid content, compared with those in the vehicle group. RNA-sequencing analysis revealed that L. plantarum treatment significantly downregulated inflammation-related pathways. Shotgun metagenomic analysis revealed that L-arginine biosynthesis-related microbial genes were significantly upregulated in the L. plantarum group. We also confirmed the elevated arginine levels in the serum of the L. plantarum group. We further used liver organoids and mice fed an MCD diet to demonstrate that L-arginine alone was sufficient to alleviate liver inflammation. Our data revealed a novel and counterintuitive therapeutic effect of L. plantarum on alleviating NASH-related liver inflammation by increasing circulating L-arginine.
Files in This Item:
T202307220.pdf Download
DOI
10.1038/s12276-023-01102-0
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Dong Yun(김동윤) ORCID logo https://orcid.org/0000-0002-2471-3385
Park, Jun Yong(박준용) ORCID logo https://orcid.org/0000-0001-6324-2224
Gee, Heon Yung(지헌영) ORCID logo https://orcid.org/0000-0002-8741-6177
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/197330
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