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<p>Demyelination is a hallmark of many central nervous system (CNS) disorders. Recent studies suspect that early-life gut microbiota disruption via antibiotic exposure may influence CNS myelination through the gut-brain axis. In this context, our study aimed to assess the long-term effects of early-life gut microbiota depletion on motor behavior, blood–brain barrier (BBB) integrity, and myelination in adult Swiss albino mice. To this end, mice received a broad-spectrum antibiotic cocktail (amoxicillin, clarithromycin, metronidazole; 75&#xa0;mg/kg/day) in drinking water for 10&#xa0;days during critical developmental windows: pre-weaning and early post-weaning periods, while controls received plain water. Adult motor function was evaluated by the rotarod and inverted screen. BBB permeability was analyzed by Evans Blue extravasation, and CNS myelination was evaluated histologically using Luxol Fast Blue staining. Our findings demonstrate that pre-weaning antibiotic exposure induced a demyelination percentage at 28.1 ± 2.4%, representing the most impacted marker, which was significantly higher than in controls and early post-weaning mice (5.6 ± 0.9%; 16.7 ± 1.9%; <i>p</i> &lt; 0.001). Rotarod and inverted screen results showed a notable reduction in motor coordination and muscle strength (<i>p</i> &lt; 0.001), while BBB permeability was elevated (<i>p</i> &lt; 0.05) in the pre-weaning group. Early post-weaning antibiotic effects were milder and not persistent. Our data suggest that early-life gut microbiota disruptions, particularly during the pre-weaning stage, cause persistent myelin impairment, BBB disruption, and motor deficits in adult mice, these observations underscore the detrimental effects of microbial imbalances on brain development.</p>

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Early-life gut microbiota depletion leads to persistent CNS myelin impairment in adult Swiss albino mice

  • 期刊论文

  • 发表日期：

    2025年10月1日

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  • Amal Dimaoui,
  • Youssef El Mekhlouf,
  • Mouloud Lamtai,
  • Laila Ibouzine-dine,
  • Zineb El Marzouki,
  • Tarik Touil,
  • Aboubaker El hessni,
  • Abdelhalem Mesfioui

摘要

Demyelination is a hallmark of many central nervous system (CNS) disorders. Recent studies suspect that early-life gut microbiota disruption via antibiotic exposure may influence CNS myelination through the gut-brain axis. In this context, our study aimed to assess the long-term effects of early-life gut microbiota depletion on motor behavior, blood–brain barrier (BBB) integrity, and myelination in adult Swiss albino mice. To this end, mice received a broad-spectrum antibiotic cocktail (amoxicillin, clarithromycin, metronidazole; 75 mg/kg/day) in drinking water for 10 days during critical developmental windows: pre-weaning and early post-weaning periods, while controls received plain water. Adult motor function was evaluated by the rotarod and inverted screen. BBB permeability was analyzed by Evans Blue extravasation, and CNS myelination was evaluated histologically using Luxol Fast Blue staining. Our findings demonstrate that pre-weaning antibiotic exposure induced a demyelination percentage at 28.1 ± 2.4%, representing the most impacted marker, which was significantly higher than in controls and early post-weaning mice (5.6 ± 0.9%; 16.7 ± 1.9%; p < 0.001). Rotarod and inverted screen results showed a notable reduction in motor coordination and muscle strength (p < 0.001), while BBB permeability was elevated (p < 0.05) in the pre-weaning group. Early post-weaning antibiotic effects were milder and not persistent. Our data suggest that early-life gut microbiota disruptions, particularly during the pre-weaning stage, cause persistent myelin impairment, BBB disruption, and motor deficits in adult mice, these observations underscore the detrimental effects of microbial imbalances on brain development.