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Early Influences of Microbiota on White Matter Development in Germ-Free Piglets
Sadia Ahmed1, Sierrah D Travis2, Francisca V Díaz-Bahamonde2
1Graduate Studies in Biomedical and Veterinary Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
Abstract:
Abnormalities in the prefrontal cortex (PFC), as well as the underlying white matter (WM) tracts, lie at the intersection of many neurodevelopmental disorders. The influence of microorganisms on brain development has recently been brought into the clinical and research spotlight as alterations in commensal microbiota are implicated in such disorders, including autism spectrum disorders, schizophrenia, depression, and anxiety via the gut-brain axis. In addition, gut dysbiosis is common in preterm birth patients who often display diffuse WM injury and delayed WM maturation in critical tracts including those within the PFC and corpus callosum. Microbial colonization of the gut aligns with ongoing postnatal processes of oligodendrogenesis and the peak of brain myelination in humans; however, the influence of microbiota on gyral WM development remains elusive. Here, we develop and validate a neonatal germ-free swine model to address these issues, as piglets share key similarities in WM volume, developmental trajectories, and distribution to humans. We find significant region-specific reductions, and sexually dimorphic trends, in WM volume, oligodendrogenesis, and mature oligodendrocyte numbers in germ-free piglets during a key postnatal epoch of myelination. Our findings indicate that microbiota plays a critical role in promoting WM development during early life when the brain is vulnerable to environmental insults that can result in an array of disabilities manifesting later in life.
Insights
Microbiota promotes white matter (WM) development in early life. Germ-free piglets showed reduced WM volume and oligodendrogenesis, indicating microbes are crucial for brain maturation.
Area of Science:
- Neuroscience
- Developmental Biology
- Microbiology
Background:
- Prefrontal cortex (PFC) and white matter (WM) abnormalities are linked to neurodevelopmental disorders.
- Gut microbiota alterations are implicated in disorders like autism, schizophrenia, depression, and anxiety via the gut-brain axis.
- Gut dysbiosis is common in preterm infants with WM injury, impacting brain maturation.
Purpose of the Study:
- To investigate the influence of microbiota on white matter (WM) development during early postnatal life.
- To address the elusive role of microbiota in gyral WM development.
- To utilize a neonatal germ-free swine model due to similarities with human brain development.
Main Methods:
- Development and validation of a neonatal germ-free swine model.
- Comparative analysis of WM volume, oligodendrogenesis, and mature oligodendrocyte numbers in germ-free versus conventionally raised piglets.
- Focus on a key postnatal period of myelination.
Main Results:
- Germ-free piglets exhibited significant, region-specific reductions in WM volume.
- Reduced oligodendrogenesis and fewer mature oligodendrocytes were observed in germ-free piglets.
- Sexually dimorphic trends in WM development were noted in the absence of microbiota.
Conclusions:
- Microbiota plays a critical role in promoting white matter (WM) development during early life.
- Early-life microbial colonization is essential for normal brain myelination and maturation.
- Findings highlight the vulnerability of the developing brain to environmental factors, including microbial exposure, and its implications for lifelong disabilities.
