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Published on: September 22, 2019
Amuc Prevents Liver Inflammation and Oxidative Stress in Mice Challenged with Salmonella Typhimurium
Zhuan Song1, Xuemeng Si2, Xinyu Zhang2
1State Key Laboratory of Animal Nutrition, Department of Companion Animal Science, China Agricultural University, Beijing, P. R. China; Beijing Jingwa Agricultural Science and Technology Innovation Center, Beijing, P. R. China.
Background:
Salmonella typhimurium is a pathogen that causes gastroenteritis in humans and animals. Amuc_1100 (hereafter called Amuc), the outer membrane protein of Akkermansia muciniphila, alleviates metabolic disorders and maintains immune homeostasis.
Objective:
This study was conducted to determine whether there is a protective effect of Amuc administration.
Methods:
Male 6-wk-old C57BL6J mice were randomly allocated into 4 groups: CON (control), Amuc (gavaged with Amuc, 100 μg/d for 14 d), ST (oral administration of 1.0 × 106 CFU S. typhimurium on day 7), and ST + Amuc (Amuc supplementation for 14 d, S. typhimurium administration on day 7). Serum and tissue samples were collected 14 d after treatment. Histological damage, inflammatory cell infiltration, apoptosis, and protein levels of genes associated with inflammation and antioxidant stress were analyzed. Data were analyzed by 2-way ANOVA and Duncan's multiple comparisons using SPSS software.
Results:
The ST group mice had 17.1% lower body weight, 1.3-3.6-fold greater organ index (organ weight/body weight for organs including the liver and spleen), 10-fold greater liver damage score, and 3.4-10.1-fold enhanced aspartate transaminase, alanine transaminase, and myeloperoxidase activities, and malondialdehyde and hydrogen peroxide concentrations compared with controls (P < 0.05). The S. typhimurium-induced abnormalities were prevented by Amuc supplementation. Furthermore, the ST + Amuc group mice had 1.44-1.89-fold lower mRNA levels of proinflammatory cytokines (interleukin [Il]6, Il1b, and tumor necrosis factor-α) and chemokines (chemokine ligand [Ccl]2, Ccl3, and Ccl8) and 27.1%-68.5% lower levels of inflammation-related proteins in the liver than ST group mice (P < 0.05).
Conclusions:
Amuc treatment prevents S. typhimurium-induced liver damage partly through the toll-like receptor (TLR)2/TLR4/myeloid differentiation factor 88 and nuclear factor-κB signaling as well as nuclear factor erythroid-2 related factor signaling pathways. Thus, Amuc supplementation may be effective in treating liver injury in S. typhimurium-challenged mice.
Insights
Amuc supplementation protected mice against Salmonella typhimurium-induced liver damage by reducing inflammation and oxidative stress. This study suggests Amuc may be an effective treatment for Salmonella-related liver injury.
Area of Science:
- Microbiology and Immunology
- Gastroenterology
- Protective protein research
Background:
- Salmonella typhimurium is a common cause of gastroenteritis in humans and animals.
- Amuc_1100 (Amuc), an outer membrane protein of Akkermansia muciniphila, is known to improve metabolic health and immune balance.
Purpose of the Study:
- To investigate the potential protective effects of Amuc against Salmonella typhimurium infection.
- To evaluate Amuc's impact on liver damage and inflammatory responses in a mouse model.
Main Methods:
- Male C57BL6J mice were divided into four groups: control, Amuc-treated, S. typhimurium-infected (ST), and ST + Amuc-treated.
- Mice received Amuc (100 μg/d) or a placebo for 14 days, with S. typhimurium administered on day 7 for the infected groups.
- Analysis included histological damage, inflammatory markers, apoptosis, and gene/protein expression related to inflammation and oxidative stress.
Main Results:
- S. typhimurium infection led to decreased body weight, increased organ index, significant liver damage, and elevated liver enzymes and oxidative stress markers compared to controls.
- Amuc supplementation effectively prevented these S. typhimurium-induced abnormalities.
- In the ST + Amuc group, mRNA levels of pro-inflammatory cytokines and chemokines, as well as liver inflammation-related proteins, were significantly reduced compared to the ST group.
Conclusions:
- Amuc treatment mitigated S. typhimurium-induced liver injury by modulating TLR2/TLR4/NF-κB and Nrf2 signaling pathways.
- Amuc supplementation demonstrates potential efficacy in treating liver damage caused by S. typhimurium infection.
