Lactobacillus plantarum ameliorates NASH-related inflammation by upregulating l-arginine production
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-med...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-11-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-023-01102-0 |
| _version_ | 1797415946664542208 |
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| author | Dong Yun Kim Jun Yong Park Heon Yung Gee |
| author_facet | Dong Yun Kim Jun Yong Park Heon Yung Gee |
| author_sort | Dong Yun Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T05:56:46Z |
| format | Article |
| id | doaj.art-efba65fffad848ac8fb9a5c6a919e98a |
| institution | Directory Open Access Journal |
| issn | 2092-6413 |
| language | English |
| last_indexed | 2024-03-09T05:56:46Z |
| publishDate | 2023-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj.art-efba65fffad848ac8fb9a5c6a919e98a2023-12-03T12:13:13ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132023-11-0155112332234510.1038/s12276-023-01102-0Lactobacillus plantarum ameliorates NASH-related inflammation by upregulating l-arginine productionDong Yun Kim0Jun Yong Park1Heon Yung Gee2Department of Pharmacology, Yonsei University College of MedicineDivision of Gastroenterology, Department of Internal Medicine, Yonsei University College of MedicineDepartment of Pharmacology, Yonsei University College of MedicineAbstract 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.https://doi.org/10.1038/s12276-023-01102-0 |
| spellingShingle | Dong Yun Kim Jun Yong Park Heon Yung Gee Lactobacillus plantarum ameliorates NASH-related inflammation by upregulating l-arginine production Experimental and Molecular Medicine |
| title | Lactobacillus plantarum ameliorates NASH-related inflammation by upregulating l-arginine production |
| title_full | Lactobacillus plantarum ameliorates NASH-related inflammation by upregulating l-arginine production |
| title_fullStr | Lactobacillus plantarum ameliorates NASH-related inflammation by upregulating l-arginine production |
| title_full_unstemmed | Lactobacillus plantarum ameliorates NASH-related inflammation by upregulating l-arginine production |
| title_short | Lactobacillus plantarum ameliorates NASH-related inflammation by upregulating l-arginine production |
| title_sort | lactobacillus plantarum ameliorates nash related inflammation by upregulating l arginine production |
| url | https://doi.org/10.1038/s12276-023-01102-0 |
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