Intestinal Microbiomics and Metabolomics Insights into the Hepatoprotective Effects of Lactobacillus paracasei CCFM1222 Against the Acute Liver Injury in Mice

Abstract

In recent years, acute liver injury (ALI) has received wide-range attention in the world due to its relatively high morbidity and mortality. This study aimed to explore the hepatoprotective effect of Lactobacillus paracasei CCFM1222 against lipopolysaccharide (LPS)-induced ALI mice, and further elaborate its mechanism of action from the perspective of intestinal microbiomics and metabolomics. The results displayed that L. paracasei CCFM1222 pretreatment signi cantly decreased the serum ALT, and AST levels, inhibited the releases of hepatic TNF-α, IL-1β, and IL-6 levels, and activated the SOD, CAT, and GSH-Px activities in LPS-treated mice. The cecal short-chain fatty acid (SCFAs) levels were increased in LPStreated mice with L. paracasei CCFM1222 pretreatment. In addition, L. paracasei CCFM1222 pretreatment remarkably shifted the intestinal microbiota composition, including the higher abundance of Faecalibaculum, Bi dobacterium, and lower abundance of Prevotellaceae NK3B31 group, which is positively associated with the cecal propionic, butyric, valeric, isobutyric, and isovaleric acids. The metabolomics based on UPLC-QTOF/MS revealed that L. paracasei CCFM1222 pretreatment signi cantly regulated the composition of feces metabolites in LPS-treated mice, especially the potential biomarkersrelated butanoate metabolism, vitamin B6 metabolism, D-glutamine and D-glutamate metabolism, tryptophan metabolism, caffeine metabolism, arginine biosynthesis, arginine, and proline metabolism. Moreover, L. paracasei CCFM1222 pretreatment remarkably regulated the expression of genes-associated ALI (including Tlr4, Myd88, Nf-kβ, iNOS, Cox2, Iκ-Bα, Nrf2, and Sirt-1). In conclusion, these results suggest the possibility that L. paracasei CCFM1222 supplementation has bene cial effects on preventing the occurrence and development of ALI by inhibiting the in ammatory responses, altering intestinal microbiota composition and their metabolites, and mediating the Tlr4/Nf-kβ pathway.

Intestinal microbiomics and hepatic metabolomics insights into the potential mechanisms of probiotic Bifidobacterium pseudolongumCCFM1253 preventing acute liver injury in mice

“…Intraperitoneal injection of LPS is an effective method for establishing the ALI model, which has been widely accepted because of its symptoms similar to clinical ALI 6 . Therefore, this model is frequently used to seek or develop probiotics, natural products, and drugs with strong hepatoprotective efficacy on patients with ALI.…”

“…Among them, mice in the CCFM1253 group received 200 μL of B. pseudolongum CCFM1253 (5.0 × 10 9 colony‐forming units mL −1 ) by oral gavage daily, and the other mice received 200 μL of sterile saline by oral gavage daily. At the end of this experiment, mice in the Control group were intraperitoneally injected with 200 μL of sterile saline after 6 h of fasting, whereas mice in the Model and CCFM1253 groups were intraperitoneally injected with 200 μL of LPS (5 mg kg −1 ) 6 . Twenty‐four mice were sacrificed after 10 h of fasting.…”

“…Despite the pathogenic mechanisms of ALI involves in multiple aspects, the abnormal levels of inflammatory cytokines are considered as one of the important reasons for accelerating the pathogenesis and processes of ALI. Lipopolysaccharide (LPS) is a toxic constituent from Gram‐negative bacteria and is widely applied to induce the secretion of inflammation cytokines, such as tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, and IL‐6 5,6 . The accumulation of inflammation cytokines in the liver elevates the risk of ALI occurrences and accelerates the process of liver diseases 7 .…”

“…Lipopolysaccharide (LPS) is a toxic constituent from Gram-negative bacteria and is widely applied to induce the secretion of inflammation cytokines, such as tumor necrosis factor (TNF)-⊍, interleukin (IL)-1⊎, and IL-6. 5,6 The accumulation of inflammation cytokines in the liver elevates the risk of ALI occurrences and accelerates the process of liver diseases. 7 Therefore, intraperitoneal injection of LPS is frequently used to induce the ALI model and has become a vital tool for revealing the pathogenesis of ALI and the development of anti-inflammation drug treatment.…”

Protective effect of Lactiplantibacillus pentosus CQZC01 in Kunming mice of subacute alcoholic liver injury

“…LAB with antioxidant capacity can protect against liver injury by upregulating the expression of Nrf2 (J. Dong et al, 2022;Guo et al, 2022;L. Zhao et al, 2017).…”