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Published on: May 1, 2013
Lentinula edodes cultured extract intake alleviates long-term immune deregulation induced by early-life gut
Roghayeh Shahbazi1, Hamed Yasavoli-Sharahi1, Mary Joe Hebbo2
1Cellular and Molecular Medicine Department, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
Insights
Early antibiotic exposure disrupts infant gut bacteria and immunity. A prebiotic, AHCC, may protect against these long-term effects by restoring microbiota balance and immune function.
Area of Science:
- Microbiology
- Immunology
- Developmental Biology
Background:
- Early-life gut microbiota establishment is vital for immune development.
- Perinatal antibiotic exposure can disrupt this critical window, leading to lasting health issues.
- Mechanisms linking early dysbiosis to long-term immune dysregulation require further investigation.
Purpose of the Study:
- To investigate the persistent effects of perinatal low-dose penicillin exposure on gut immunity.
- To evaluate the protective potential of a prebiotic, AHCC (Lentinula edodes cultured extract), against antibiotic-induced gut dysbiosis and immune dysregulation.
Main Methods:
- Pregnant mice received penicillin and AHCC from gestation through pup weaning.
- Offspring gut microbiota, immune function, and microRNA (miRNA) profiles were assessed at eight weeks.
- Microbiome analysis, cytokine profiling, and miRNA expression analysis were performed.
Main Results:
- Penicillin exposure altered gut microbiota, increasing Proteobacteria and decreasing beneficial Firmicutes, Lactobacillus, and SCFA-producing bacteria.
- AHCC intake counteracted antibiotic-induced changes in Proteobacteria and certain SCFA-producing bacteria in male offspring.
- AHCC modulated immune responses by reducing pro-inflammatory cytokines (IL-2, IL-6, IL-15, IL-21) and mitigating NF-κB activation.
- Antibiotic exposure dysregulated gut miRNA expression (increased miR-221, decreased miR-145 in males); AHCC prevented miR-145 alterations.
Conclusions:
- Perinatal antibiotic exposure causes persistent gut microbiota and immune alterations.
- Prebiotic AHCC shows promise in preventing and mitigating antibiotic-induced dysbiosis and immune dysregulation.
- Targeting early-life gut microbiota with prebiotics may be a viable strategy for long-term health maintenance.
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.
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