L-arabinose Attenuates LPS-Induced Intestinal Inflammation and Injury through the Reduced M1 Macrophage Polarization.

BACKGROUND: L-arabinose has anti-inflammatory and metabolism-promoting properties, and macrophages participate in the alleviation of inflammation; however, the mechanism by which they contribute to the anti-inflammatory effects of L-arabinose is unknown.

OBJECTIVES: To investigate the involvement of macrophages in the mitigation of L-arabinose in an intestinal inflammation model induced by lipopolysaccharide (LPS).

METHODS: Five-week-old male C57BL/6 mice were divided into three groups: a control and an LPS group that both received normal water supplementation, and an L-arabinose (ARA+LPS) group that received 5% L-arabinose supplementation. Mice in the LPS and ARA+LPS groups were intraperitoneally injected with LPS (10 mg/kg body weight), whereas the control group was intraperitoneally injected with the same volume of saline. Intestinal morphology, cytokines, tight junction proteins, macrophage phenotypes, and microbial communities were profiled at 6 h post-injection.

RESULTS: L-arabinose alleviated LPS-induced damage to intestinal morphology. L-arabinose down-regulated serum TNF-α, IL-1β, and IL-6, and mRNA levels of TNF-α, IL-1β, IFN-γ, and TLR-4 in jejunum and colon compared to those of the LPS group (P < 0.05). The mRNA and protein levels of occludin and claudin-1 were significantly increased by L-arabinose (P < 0.05). IRF-5 and STAT-1, key genes characterized by M1 macrophages, were elevated in the jejunum and colon of LPS mice (P < 0.05) but decreased in the ARA+LPS mice (P < 0.05). In vitro, L-arabinose decreased the proportion of M1 macrophages and inhibited mRNA levels of TNF-α, IL-1β, IL-6, IFN-γ, as well as IRF-5 and STAT-1 (P < 0.01). Moreover, L-arabinose restored the abundance of Norank_f__Muribaculaceae, Faecalibaculum, Dubosiella, Prevotellaceae_UCG-001, and Paraasutterella compared to those of LPS (P < 0.05) and increased the concentration of SCFAs (P < 0.05).

CONCLUSION: The anti-inflammatory effects of L-arabinose were achieved by reducing M1 macrophage polarization, suggesting that L-arabinose could be a candidate functional food or nutritional strategy for intestinal inflammation and injury.