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

• Published in: Experimental & molecular medicine Vol. 55; no. 11; pp. 2332 - 2345
• Main Authors: Kim, Dong Yun, Park, Jun Yong, Gee, Heon Yung
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2023; Springer Nature B.V; Nature Publishing Group; 생화학분자생물학회
• Subjects: 38/91; 45/23; 64/60; 692/699/1503/1607/2751; 692/700/565/1331; Animal models; Animals; Arginine; Biomedical and Life Sciences; Biomedicine; Biosynthesis; Choline; Choline - metabolism; Diet, High-Fat - adverse effects; Digestive system; Disease Models, Animal; Fatty liver; Gastrointestinal tract; Hepatitis - pathology; High fat diet; Humans; Immunohistochemistry; Inflammation; Inflammation - metabolism; Intestinal microflora; Lactobacillus plantarum; Lactobacillus plantarum - metabolism; Liver - metabolism; Liver diseases; Medical Biochemistry; Metabolic syndrome; Metabolism; Metagenomics; Methionine; Mice; Mice, Inbred C57BL; Microbiota; Molecular Medicine; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - etiology; Nutrient deficiency; Organoids; Phenotypes; Probiotics; Sequence analysis; Stem Cells; Transcriptomics; 생화학
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/s12276-023-01102-0

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. Revolutionary Breakthrough: L. Plantarum Probiotic Alleviates Liver Inflammation Lactobacillus plantarum , a beneficial gut bacteria, shows potential in treating non-alcoholic fatty liver disease (NAFLD) by increasing L-arginine levels and reducing liver inflammation. Researchers used a choline-deficient high-fat diet-induced NAFLD mouse model to study the effects of L. plantarum treatment. Results showed that L. plantarum administration ameliorated liver inflammation and enhanced L-arginine biosynthesis in the intestine. Furthermore, L-arginine treatment also improved liver inflammation in methionine-choline deficient-induced NAFLD mice. These findings suggest that L. plantarum could be a promising therapeutic strategy for NAFLD by increasing L-arginine levels and modulating gut microbiota, improving intestinal barrier integrity, and attenuating inflammation.