Alginate Oligosaccharide Alleviates Salmonella Typhimurium-Induced Liver Injury by Regulating Oxidative Stress, Apoptosis, and Inflammatory Signaling Pathway.

Abstract

Alginate oligosaccharide (AOS) is a kind of functional oligosaccharides obtained from the degradation of alginate, which has functional properties such as anti-inflammatory, antibacterial, and antioxidant activity. The aim of this study was to investigate whether AOS could alleviate Salmonella enterica serovar Typhimurium (S. Typhimurium)-induced liver injury. In our study, we found that AOS could alleviate S. Typhimurium-caused weight loss, enlargement of the liver and spleen in mice. In addition, AOS attenuated S. Typhimurium-induced inflammatory response as evidenced by the reduced ratio of AST/ALT, and lower the mRNA levels of Il-6, Il-1β, Tnf-α, Ccl3, and Ccl8. Moreover, AOS reduced H₂O₂ activity and Ho-1 gene expression. TUNEL staining and Western blot results showed that AOS reduced S. Typhimurium-induced hepatic apoptosis. Further study showed that AOS suppressed S. Typhimurium-induced increase in gene expression levels of Tlr2, Tlr4, and Myd88 as well as protein expression levels of TLR2 and p-NF-κB p65. The 16S rRNA results of colonic contents showed that AOS increased the relative abundance of Lactobacillus and decreased Alistipes, Helicobacter, and Bacteroides. Analyses at the species level showed that the AOS + ST group increased the abundance of Lactobacillus johnsonii (L. johnsonii) and Limosilactobacillus reuteri (formely Lactobacillus reuteri, L. reuteri). In addition, Lactobacillus johnsonii culture supernatant and Limosilactobacillus reuteri culture supernatant partially reduced gene expression levels of pro-inflammatory cytokines and chemokines induced by lipopolysaccharide. In conclusion, the alleviation of S. Typhimurium-induced liver injury by AOS may be related to the reduction of inflammatory response, oxidative stress, apoptosis, and regulation of the gut microbiota.