Abstract
Emerging evidence indicates that probiotics have been proved to influence liver injury and regeneration. In the present study, the effects of Lactiplantibacillus plantarum AR113 on the liver regeneration were investigated in 70% partial hepatectomy (PHx) rats. Sprague-Dawley (SD) rats were gavaged with L. plantarum AR113 suspensions (1 × 1010 CFU/mL) both before and after partial hepatectomy. The results showed that L. plantarum AR113 administration 2 weeks before partial hepatectomy can accelerate liver regeneration by increased hepatocyte proliferation and tumor necrosis factor-α (TNF-α), hepatocyte growth factor (HGF), and transforming growth factor-β (TGF-β) expression. Probiotic administration enriched Lactobacillus and Bacteroides and depleted Flavonifractor and Acetatifactor in the gut microbiome. Meanwhile, L. plantarum AR113 showed decline of phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidyl serine (PS), and lysophosphatidyl choline (LysoPC) levels in the serum of the rats after the L. plantarum AR113 administration. Moreover, L. plantarum AR113 treated rats exhibited higher concentrations of L-leucine, L-isoleucine, mevalonic acid, and lower 7-oxo-8-amino-nonanoic acid in plasma than that in PHx. Spearman correlation analysis revealed a significant correlation between changes in gut microbiota composition and glycerophospholipid. These results indicate that L. plantarum AR113 is promising for accelerating liver regeneration and provide new insights regarding the correlations among the microbiome, the metabolome, and liver regeneration.
Highlights
Liver diseases are a major medical problem for health care systems worldwide (Chowdhury et al, 2021)
In order to investigate the effect of L. plantarum AR113 administration on liver regeneration, hepatocyte proliferation and hepatic regeneration rate were analyzed
Because the proliferation of liver cells occurs within 3 days after surgery, there was no significant difference in cell proliferation rates between the 70% partial hepatectomy (PHx) group and L. plantarum AR113 pretreatment group at 7 days after PHx (Supplementary Table 1)
Summary
Liver diseases are a major medical problem for health care systems worldwide (Chowdhury et al, 2021). Partial hepatectomy and liver transplantation are currently the only curable methods for patients with hepatocellular carcinoma and cirrhosis (Yagi et al, 2020). The liver’s remarkable capacity to regenerate after surgery determines the long-term prognosis and quality of life of patients. Liver regeneration is an orchestrated biological process that includes sequential changes in gene expression, growth factor production, and tissue remodeling (Michalopoulos and Bhushan, 2021). Hepatocytes, which are not terminally differentiated, exhibit substantial proliferative capacity. Notably HGF, epidermal growth factor, transforming growth factor-α (TGF-α), interleukin-6 (IL-6), and TNF-α, which are involved in liver regeneration, have been identified and extensively reviewed (Hoffmann et al, 2020). Liver regeneration research has typically focused on signaling pathways intrinsic to the liver, overlooking those derived from the gut
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