Dataset Information

Lactobacillus reuteri mitigates hepatic ischemia/reperfusion injury by modulating gut microbiota and metabolism through the Nrf2/HO-1 signaling.

ABSTRACT:

Background

This study seeks to investigate the impacts of Lactobacillus reuteri (L. reuteri) on hepatic ischemia-reperfusion (I/R) injury and uncover the mechanisms involved.

Methods

Mice in the I/R groups were orally administered low and high doses of L.reuteri (L.reuteri-low and L. reuteri-hi; 1 × 10¹⁰ CFU/d and 1 × 10¹¹ CFU/d), for 4 weeks prior to surgery. Following this, mice in the model group were treated with an Nrf2 inhibitor (ML-385), palmitoylcarnitine, or a combination of both.

Results

After treatment with L. reuteri, mice exhibited reduced levels of serum aminotransferase (ALT), aspartate aminotransferase (AST), and myeloperoxidase (MPO) activity, as well as a lower Suzuki score and apoptosis rate. L. reuteri effectively reversed the I/R-induced decrease in Bcl2 expression, and the significant increases in the levels of Bax, cleaved-Caspase3, p-p65/p65, p-IκB/IκB, p-p38/p38, p-JNK/JNK, and p-ERK/ERK. Furthermore, the administration of L. reuteri markedly reduced the inflammatory response and oxidative stress triggered by I/R. This treatment also facilitated the activation of the Nrf2/HO-1 pathway. L. reuteri effectively counteracted the decrease in levels of beneficial gut microbiota species (such as Blautia, Lachnospiraceae NK4A136, and Muribaculum) and metabolites (including palmitoylcarnitine) induced by I/R. Likewise, the introduction of exogenous palmitoylcarnitine demonstrated a beneficial impact in mitigating hepatic injury induced by I/R. However, when ML-385 was administered prior to palmitoylcarnitine treatment, the previously observed effects were reversed.

Conclusion

L. reuteri exerts protective effects against I/R-induced hepatic injury, and its mechanism may be related to the promotion of probiotic enrichment, differential metabolite homeostasis, and the Nrf2/HO-1 pathway, laying the foundation for future clinical applications.

SUBMITTER: Zhang L

PROVIDER: S-EPMC10946149 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

Lactobacillus reuteri mitigates hepatic ischemia/reperfusion injury by modulating gut microbiota and metabolism through the Nrf2/HO-1 signaling.

Zhang Leiyi L Gong Xiaoxiang X Tan Juan J Zhang Rongsen R Li Mingxia M Liu Cong C Wu Chenhao C Li Xiaojing X

Biology direct 20240318 1

<h4>Background</h4>This study seeks to investigate the impacts of Lactobacillus reuteri (L. reuteri) on hepatic ischemia-reperfusion (I/R) injury and uncover the mechanisms involved.<h4>Methods</h4>Mice in the I/R groups were orally administered low and high doses of L.reuteri (L.reuteri-low and L. reuteri-hi; 1 × 10<sup>10</sup> CFU/d and 1 × 10<sup>11</sup> CFU/d), for 4 weeks prior to surgery. Following this, mice in the model group were treated with an Nrf2 inhibitor (ML-385), palmitoylcarni ...[more]

PMID: 38500127

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Project description:BackgroundLycopene is a naturally occurring carotenoid found in many fruits and vegetables, which has antioxidant effects. Although lycopene's protective effect has been observed on ischemia reperfusion (IR) injury in different organs, the effect of lycopene on Kupffer cells (KCs) has not been clearly elucidated in IR-induced acute hepatic inflammatory injury.MethodsMice were administered with either olive oil (10 mL/kg body weight) as the control or lycopene (20 mg/kg body weight) by gavage for 2 weeks before undergoing hepatic IR injury.ResultsIn this study, we observed that the levels of aspartate aminotransferases (AST), alanine aminotransferase (ALT), and the percentages of hepatocellular apoptosis in mice pretreated with lycopene were significantly lower than control mice. Lycopene inhibited F4/80+ macrophage and Ly6G+ neutrophil accumulation, which further decreased the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin 6 (IL-6). Interestingly, lycopene induced increased autophagy in KCs, which was evidenced by elevated autophagosomes and the increased protein level of LC3B. In these KCs, lycopene-induced upregulation of autophagy inhibited NOD-like receptor family pyrin domain-containing 3 protein (NLRP3) inflammasome activation, which was demonstrated by the reduced mRNA and protein levels of NLRP3, cleaved caspase-1, an apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and IL-1β. Furthermore, 3-methyladenine, an autophagy inhibitor, abolished lycopene's inhibitory effect on the NLRP3 inflammasome in KCs, which led to increased hepatic IR injury. Intriguingly, we identified that the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) were elevated in KCs isolated from IR-stressed mice pretreated with lycopene. Nrf2-siRNA or HO-1-siRNA could block the autophagy activation enhanced by lycopene in KCs, resulting in the activation of the NLRP3 inflammasome and aggravated hepatic IR injury.ConclusionsOur findings demonstrated that lycopene promoted Nrf2/HO-1 pathway activation and further suppressed the NLRP3 inflammasome via enhancing KC autophagy, which alleviated hepatic IR injury.

Project description:BackgroundSevoflurane can protect organs from ischemia-reperfusion (IR) injury, but the mechanism is still unclear. MicroRNA-122 (miR-122) is a liver-specific microRNA (miRNA) and regulates liver function. Therefore, this study aims to elucidate the relationship between the protective effect of sevoflurane and miR-122 in liver IR injury.MethodsWistar rats were divided into the following groups: sham, IR, IR + sevoflurane, IR + miR-122 antagomir, and IR + miR-122 antagomir + sevoflurane. Hematoxylin and eosin (H&E) staining and Suzuki score were used to evaluate the pathological damage of the liver. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 in the serum and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) in the liver homogenate supernatant were detected by using the corresponding kit. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) and flow cytometry was applied to evaluate the apoptosis of liver tissues. The expression of nuclear factor E2-related factor 2 (Nrf2), miR-122, p53, and HO-1 in liver tissue was evaluated by using immunohistochemistry, qRT-PCR, and western blot as needed.ResultsCompared to the IR group, the sevoflurane post-treatment or miR-122 antagomir groups showed improved liver injury, decreased Suzuki score, inhibited the levels of AST, ALT, LDH, MDA, NO, TNF-α, IL-1β, and IL-6, increased levels of SOD, IL-10, and inhibited hepatocyte apoptosis. Regarding the molecular mechanism, sevoflurane post-treatment fostered the expression of HO-1, promoted the transport of Nrf2 from cytoplasm to the nucleus, and decreased the expression of miR-122 and p53. The combined use of miR-122 antagomir and sevoflurane enhanced the protective effect of miR-122 antagomir in liver injury in IR rats.ConclusionsSevoflurane protected the liver from IR damage by regulating the miR-122/Nrf2/HO-1 pathway.

Dataset Information

Lactobacillus reuteri mitigates hepatic ischemia/reperfusion injury by modulating gut microbiota and metabolism through the Nrf2/HO-1 signaling.

Background

Methods

Results

Conclusion

Publications

Lactobacillus reuteri mitigates hepatic ischemia/reperfusion injury by modulating gut microbiota and metabolism through the Nrf2/HO-1 signaling.

Similar Datasets

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