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

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. To investigate the involvement of macrophages in the mitigation of L-arabinose in an intestinal inflammation model induced by lipopolysaccharide (LPS). Five-week-old male C57BL/6 mice were divided into 3 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 postinjection. L-arabinose alleviated LPS-induced damage to intestinal morphology. L-arabinose down-regulated serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, and messenger RNA (mRNA) levels of TNF-α, IL-1β, interferon-γ ( IFN-γ ), and toll-like receptor-4 in jejunum and colon compared with 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). Interferon regulatory factor-5 ( IRF-5 ) and signal transducer and activator of transcription-1 ( 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 with those of LPS ( P < 0.05) and increased the concentration of short-chain fatty acids ( P < 0.05). The anti-inflammatory effects of L-arabinose are achieved by reducing M1 macrophage polarization, suggesting that L-arabinose could be a candidate functional food or nutritional strategy for intestinal inflammation and injury.