Germ-free piglets display variable neuroinflammatory-like perturbations in prefrontal cortical microglia.
| Title: | Germ-free piglets display variable neuroinflammatory-like perturbations in prefrontal cortical microglia. |
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| Authors: | Lester BA; School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 USA.; Kelly C; Graduate Program in Translational Biology, Medicine, and Health, Virginia Polytechnic Institute and State University, Roanoke, VA 24016 USA.; Henry SN; Department of Pathobiology and Biomedical Sciences, Virginia-Maryland, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 USA.; Elias IP; Department of Pathobiology and Biomedical Sciences, Virginia-Maryland, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 USA.; Cevenini SE; Department of Pathobiology and Biomedical Sciences, Virginia-Maryland, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 USA.; Hendrickson MR; Department of Pathobiology and Biomedical Sciences, Virginia-Maryland, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 USA.; Park T; Department of Pathobiology and Biomedical Sciences, Virginia-Maryland, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 USA.; Ashley TD; Department of Pathobiology and Biomedical Sciences, Virginia-Maryland, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 USA.; Beltz JM; Department of Pathobiology and Biomedical Sciences, Virginia-Maryland, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 USA.; Milner JP; School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 USA.; Pickrell AM; School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 USA.; Morton PD; Department of Pathobiology and Biomedical Sciences, Virginia-Maryland, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 USA. |
| Source: | BioRxiv : the preprint server for biology [bioRxiv] 2026 Mar 24. Date of Electronic Publication: 2026 Mar 24. |
| Publication Type: | Journal Article; Preprint |
| Language: | English |
| Journal Info: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| Abstract: | Communication between gut microbiota and immune cells within the brain is essential for neurotypical development. Specifically, microglia are known to play a key role in regulating and supporting neural progenitor stem cell production during brain development, and are sensitive to changes in the maternal gut microbial composition during perinatal development. Here, we employed a germ-free (GF) porcine paradigm to examine how the absence of the microbiome affects microglial dynamics during a key epoch of brain development. We utilized automated software to evaluate microglial density and morphology across three developmentally significant regions: the ventricular/subventricular zone (VZ/SVZ), the prefrontal subcortical white matter (PFCSWM), and layers II/III of the prefrontal cortex (PFCII-III). We found no significant differences in microglial morphology or density in the VZ/SVZ or PFCSWM. In contrast, the PFCII-III of P16 piglets exhibited an increase in microglia density paired with morphologies indicative of an activated/reactive functional state. Notably, these effects were identified with no overall changes in microglial density in any of the regions assessed. Transcriptomics on RNA isolated from the PFCII-III revealed a significant upregulation of genes related to neuroinflammation, in agreement with a region-specific microglial and immune response in the absence of microbial colonization during postnatal development. Together, these findings build on the limited knowledge available on how microbiota influence brain development in large animal model organisms with high similarities to human brain anatomy and developmental trajectories. |
| Competing Interests: | Declaration of Interests: The authors declare no competing interests. |
| Entry Date(s): | Date Created: 20260403 Date Completed: 20260413 Latest Revision: 20260413 |
| Update Code: | 20260413 |
| PubMed Central ID: | PMC13041821 |
| DOI: | 10.64898/2026.03.22.713463 |
| PMID: | 41929228 |
| Database: | MEDLINE |
Journal Article; Preprint