Amuc Prevents Liver Inflammation and Oxidative Stress in Mice Challenged with Salmonella Typhimurium

Zhuan Song; Xuemeng Si; Xinyu Zhang; Jingqing Chen; Hai Jia; Yu He; Haozhen Liu; Zongyue Kou; Zhaolai Dai; Zhenlong Wu

doi:10.1016/j.tjnut.2022.12.004

Amuc Prevents Liver Inflammation and Oxidative Stress in Mice Challenged with Salmonella Typhimurium

J Nutr. 2023 Feb;153(2):532-542. doi: 10.1016/j.tjnut.2022.12.004. Epub 2022 Dec 25.

Authors

Zhuan Song¹, Xuemeng Si², Xinyu Zhang², Jingqing Chen³, Hai Jia², Yu He², Haozhen Liu², Zongyue Kou², Zhaolai Dai², Zhenlong Wu⁴

Affiliations

¹ State 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.
² State Key Laboratory of Animal Nutrition, Department of Companion Animal Science, China Agricultural University, Beijing, P. R. China.
³ State Key Laboratory of Animal Nutrition, Department of Companion Animal Science, China Agricultural University, Beijing, P. R. China; Laboratory Animal Center of the Academy of Military Medical Sciences, Beijing, P. R. China.
⁴ State 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. Electronic address: bio2046@hotmail.com.

PMID: 36894245
DOI: 10.1016/j.tjnut.2022.12.004

Abstract

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.

Keywords: Amuc; Salmonella typhimurium; inflammation; liver injury; oxidative stress.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Body Weight
Inflammation / metabolism
Interleukin-6 / metabolism
Liver / metabolism
Liver Diseases*
Male
Membrane Proteins / metabolism
Mice
Oxidative Stress
Salmonella typhimurium* / metabolism

Substances

Interleukin-6
Membrane Proteins