Panose prevents acute-on-chronic liver failure by reducing bacterial infection in mice
Jiaxin Li, … , Jinjun Chen, Peng Chen
Jiaxin Li, … , Jinjun Chen, Peng Chen
Published June 6, 2025
Citation Information: J Clin Invest. 2025;135(14):e184653. https://doi.org/10.1172/JCI184653.
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Research Article Hepatology Metabolism Microbiology

Panose prevents acute-on-chronic liver failure by reducing bacterial infection in mice

Abstract

Acute-on-chronic liver failure (ACLF) is a leading cause of global liver-related mortality. Bacterial infection, especially in patients with decompensated cirrhosis, commonly triggers ACLF and is difficult to treat with antibiotics. Therefore, finding alternative strategies for preventing and managing bacterial infection is an urgent priority. Here, we observed that patients with bacterial infection and decompensated cirrhosis, as well as ACLF mice, exhibited lower fecal panose levels than uninfected controls. Megamonas funiformis, with 4α-glucanosyltransferase (4αGT) as a key enzyme for panose production, was identified as a potential panose producer. Animal experiments demonstrated that panose efficiently reduced liver injury and extended survival in ACLF mice by mitigating bacterial infection. Further results revealed that panose enhanced resistance to bacterial infection by inhibiting oxidative stress–induced gut barrier disruption, thereby limiting bacterial dissemination. Mechanistically, panose interacted with the solute carrier family 7 member 11 (SLC7A11, also known as xCT) protein to boost antioxidant glutathione levels in intestinal epithelial cells. These findings highlight panose’s potential in preventing bacterial infection, offering a valuable insight into mitigating ACLF progression.

Authors

Jiaxin Li, Shihao Xie, Meiling Chen, Changze Hong, Yuqi Chen, Fengyuan Lyu, Niexin Tang, Tianqi Chen, Lingyan Zhao, Weihao Zou, Hongjuan Peng, Jingna Bao, Peng Gu, Bernd Schnabl, Jinjun Chen, Peng Chen

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Figure 6

Panose ameliorates gut barrier dysfunction by inhibiting oxidative stress.

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Panose ameliorates gut barrier dysfunction by inhibiting oxidative stres...
(A) ROS levels in ileum sections of ACLF mice were visualized with DHE staining and quantified using MFI (red: ROS; blue: DAPI-stained nuclei). Scale bar: 50 μm (n = 3–7/group). (B) MDA, SOD, and GSH levels in the ileum tissue of ACLF mice (n = 3–10/group). (C) The mRNA levels of antioxidant markers (Gpx-1, Gpx-2, Prdx-1, and Prdx-4) in the ileum tissue were determined by RT-qPCR (n = 6/group). (D) Representative images and quantification of GFP–E. coli fluorescence intensity in the liver of ACLF mice after ROS elimination via NAC (green: GFP–E. coli; blue: DAPI-stained nuclei). Scale bar: 20 μm (n = 5–6/group). (E–I) Mode-K cells were exposed to H2O2-induced oxidative stress for 12 hours before sample collection and analysis. (E) Intracellular ROS levels were assessed using DCFH-DA staining, measured by flow cytometry, and quantified with MFI (n = 3–6/group). (F) MDA, SOD, and GSH levels in the Mode-K cells (n = 3–6/group). (G) The mRNA levels of antioxidant markers (Gpx-1, Gpx-2, Prdx-1, and Prdx-4) in the Mode-K cells were determined by RT-qPCR (n = 6/group). (H) Western blot analysis and (I) quantification of ZO-1 and occludin protein expression (n = 4/group). Data are presented as mean ± SEM. Statistical significance was determined by 1-way ANOVA with Bonferroni’s post hoc test. *P < 0.05. NS, nonsignificant. DHE, dihydroethidium; MDA, malondialdehyde; SOD, superoxide dismutase; GSH, glutathione; Gpx-1, glutathione peroxidase 1; Gpx-2, glutathione peroxidase 2; Prdx-1, peroxiredoxin 1; Prdx-4, peroxiredoxin 4; NAC, N-acetylcysteine; DCFH-DA, 2′,7′-dichlorodihydrofluorescein diacetate.