Intestinal ischemia–reperfusion (I/R) injury is
a serious
disease in medical settings, and gut dysbiosis is a major contributor
to its development. Polysaccharides from Agaricus blazei Murill (ABM) showed a range of pharmacological activities, yet no
studies assessed the potential of ABM polysaccharides for alleviating
intestinal I/R injury. Here, we purified a major polysaccharide (ABP1)
from an ABM fruit body and subsequently tested its potential to mitigate
intestinal I/R injury in a mouse model of temporary superior mesenteric
artery occlusion. The results reveal that ABP1 pretreatment enhances
gut barrier function via upregulation of the expression of tight junction
proteins such as ZO-1 and occludin. Additionally, ABP1 intervention
reduces the recruitment of neutrophils and the polarization of M1
macrophages and limits inflammation by blocking the assembly of the
NLRP3 inflammasome. Moreover, the role of ABP1 in regulating the gut
microbiota was confirmed via antibiotic treatment. The omics data
reveals that ABP1 reprograms gut microbiota compositions, characterized
by a decrease of Proteobacteria and an increase of Lachnospiraceae
and Lactobacillaceae, especially the SCFA-producing genera such as Ligilactobacillus and Blautia. Overall,
this work highlights the therapeutic potential of ABP1 against intestinal
I/R injury, which mainly exhibits its effects via regulating the gut
microbiota and suppressing the overactivated inflammation response.