Lactiplantibacillus plantarum AR113 Exhibit Accelerated Liver Regeneration by Regulating Gut Microbiota and Plasma Glycerophospholipid

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.

Signaling pathways of liver regeneration: Biological mechanisms and implications

“… 68 Studies have exhibited that increasing TNF-α expression enhanced hepatocyte proliferation and accelerated LR in PHx rats. 69 Zhang et al. reported that MiR-199a was an important regulator of TNF-α signaling pathway, which regulated LR and hepatocyte proliferation in rats by targeting TNF-α/TNFR1 pathway.70 As demonstrated by Lee et al., human placental hydrolyzate (hPH) activated TNF-α pathway through activating TNF-α secretion in KCs, thereby promoting LR in rats.…”

Gut microbiome, metabolome and alopecia areata

“…Similarly, nisin, cecropin, and P. chinense have both the ability to change the abundance and composition of the fish gut microbiota and affect the expression of some anti-inflammatory cytokines, such as TGF-β ( Ke et al, 2021 ). Probiotics such as Lactobacillus plantarum AR113 could influence liver generation by increasing the expression of TNF-α, HGF and TGF-β ( Xie et al, 2021 ). All these experimental results indicate that there are correlations between the gut microbiota and the TGF-β signaling pathway; however, functional gain- and loss-of-function experiments are still lacking to confirm the direct relationship between the gut microbiome or metabolome and the TGF-β signaling pathway.…”

The role of gut microbiota in liver regeneration

“…Listeria monocytogenes, a pathogenic bacterium can be found in various kinds of food, can enhance the effect of HGF through producing bacterial HGF receptor agonist InlB321/15 and thus promote liver regeneration after 70% PH ( 61 ). Lactiplantibacillus plantarum AR113 administration showed decline of phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidyl serine (PS), and lysophosphatidyl choline (LysoPC) levels in the serum of the rats and increase HGF secretion in liver after 70% PH ( 62 ). Although the correlation of gut microbiota and HGF has been well addressed, the detailed mechanism is need to be further investigated.…”