Lentinula edodes cultured extract intake alleviates long-term immune deregulation induced by early-life gut microbiota dysbiosis.

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Citation abstract

The establishment of gut microbiota during early life is crucial for immune system development and its disturbance within this critical period exerts enduring adverse effects on health. Perinatal antibiotic exposure perturbs early-life microbiota and leads to long-term immune dysregulation. However, the underlying mechanisms remain inadequately explored. We investigated the persistent consequences of perinatal exposure to low-dose penicillin on gut immunity and the potential protective role of a prebiotic compound, Lentinula edodes cultured extract referred to as AHCC, against antibiotic-induced dysbiosis and immune dysregulation. Pregnant mice were subjected to penicillin and AHCC treatment from the third week of gestation until weaning of pups. Subsequently, the offspring were evaluated for gut microbiota at weaning as well as immune function, and microRNA (miRNA) changes at eight weeks of age. Microbiome analysis revealed substantial alterations in gut microbiota composition, characterized by an increase in Proteobacteria and a decrease in Firmicutes following antibiotic exposure. Lactobacillus, and some short-chain fatty acid (SCFA)-producing species were diminished by the antibiotic. AHCC intake prevented antibiotic effects on Proteobacteria in dams and offspring and some SCFA-producing bacteria in male offspring. In adult offspring, AHCC exhibited immunomodulatory activity by decreasing pro-inflammatory cytokines, including IL-2, IL-6, IL-15, and IL-21. In addition, antibiotic-induced increase in NF-κB was mitigated by AHCC. Early-life antibiotic exposure altered gut miRNA expression, increasing pro-inflammatory miR-221 and decreasing anti-inflammatory miR-145 in males while AHCC intake prevented antibiotic-mediated dysregulation of miRNA-145. These results highlight the potential of prebiotic intake as a promising strategy to prevent and mitigate persistent health issues arising from early-life dysbiosis.