Alginate Oligosaccharide Attenuates Lipopolysaccharide-Induced Intestinal Barrier Dysfunction in Balb/c Mice: Mechanistic Insights

Abstract

Alginate oligosaccharide (AOS) is a structurally distinct carbohydrate derived from marine algae. In this study, AOS was obtained through the enzymatic hydrolysis of alginate, and the anti-inflammatory efficacy of AOS was assessed in lipopolysaccharide (LPS)-induced inflammatory Balb/c mice. AOS effectively suppressed the overexpression of TNF-α, IL-6, and MDA while restoring the reduced SOD activity. Histopathological analysis revealed that AOS significantly reduced the level of LPS-induced tissue edema, inflammatory infiltration, and villous destruction. Additionally, AOS notably upregulated tight junction proteins Claudin-1, Occludin, and ZO-1 expression. Transcriptomic and Western blot analyses indicated that AOS primarily mediated the restriction of the TLR4/MAPK/NF-κB pathway in the jejunum. Moreover, AOS ameliorated gut microbiota dysbiosis, such as increasing in Bacteroidota, alongside decreasing in Firmicutes, Campylobacter, and Desulfovibrio, respectively. Metabolomics demonstrated that AOS improved the LPS-induced reduction of short-chain fatty acids in the gut. These results provide compelling evidence supporting the potential of AOS against acute intestinal inflammation.

Keywords: alginate oligosaccharide (AOS); gut microbiota; intestinal inflammation; lipopolysaccharide (LPS); signaling pathway.