Alginate oligosaccharide ameliorates azithromycin-induced gut microbiota disorder via Bacteroides acidifaciens-FAHFAs and Bacteroides-TCA cycle axes

Alginate oligosaccharide is a kind of prebiotic with broad application prospects. However, little attention is paid to the recovery effect of alginate oligosaccharide on disordered intestinal microecology caused by azithromycin. Therefore, we evaluated the regulatory effect of alginate oligosaccharide and its compound on azithromycin-disturbed gut microbiota in mice via microbiome-metabolomics analysis. The gut microbiota analysis revealed that alginate oligosaccharide and its compound significantly increased the richness and diversity of the gut microbiota which were reduced by azithromycin, with an obvious enrichment of beneficial bacteria such as the Akkermansia genus and Bacteroides acidifaciens, and a remarkable decrease of pathogenic bacteria such as the Staphylococcus genus, which indicated its impact on the gut microbiota dysbiosis. Additionally, the effect of the alginate oligosaccharide compound on regulating the gut microbiota disorder is more significant than that of alginate oligosaccharide. The favorable effects of alginate oligosaccharide were confirmed by beneficial alterations in metabolic effector molecules, which indicated that alginate oligosaccharide and its compound improved metabolic homeostasis via the Bacteroides acidifaciens-fatty acid esters of hydroxy fatty acids (FAHFAs) axis and increasing the levels of the intermediate products of the tricarboxylic acid cycle (TCA cycle), such as citric acid, fumaric acid and α-ketoglutaric acid. Spearman correlation analysis showed that the contents of these three metabolites were also positively related to Bacteroides acidifaciens and Bacteroides sartorii populations, suggesting the potential regulatory role of the Bacteroides genus in energy balance through the TCA cycle. This study may provide an innovative dietary strategy for the regulation of intestinal microecological disorders caused by antibiotics, and reveal the prospect of alginate oligosaccharide as an intestinal microecological regulator.