Abstract

We investigated the contributions of commensal bacteria to brain structural maturation by magnetic resonance imaging and behavioral tests in four and 12 weeks old C57BL/6J specific pathogen free (SPF) and germ free (GF) mice. SPF mice had increased volumes and fractional anisotropy in major gray and white matter areas and higher levels of myelination in total brain, major white and grey matter structures at either four or 12 weeks of age, demonstrating better brain maturation and organization. In open field test, SPF mice had better mobility and were less anxious than GF at four weeks. In Morris water maze, SPF mice demonstrated better spatial and learning memory than GF mice at 12 weeks. In fear conditioning, SPF mice had better contextual memory than GF mice at 12 weeks. In three chamber social test, SPF mice demonstrated better social novelty than GF mice at 12 weeks. Our data demonstrate numerous significant differences in morphological brain organization and behaviors between SPF and GF mice. This suggests that commensal bacteria are necessary for normal morphological development and maturation in the grey and white matter of the brain regions with implications for behavioral outcomes such as locomotion and cognitive functions.

Highlights

  • Microbial communities in the infant intestine, or the intestinal microbiota, are increasingly considered as a modifiable factor to influence the development of brain and host behavior [1,2,3,4]

  • Novel aspects of the study were to apply a combination of function-focusing modalities with complementary immunohistological studies to examine the effects of commensal bacteria on brain structure and behaviors in C57BL/6J mice

  • Novel quantitative macromolecule fraction magnetic resonance imaging (MRI) mapping was used to evaluate the impact of commensal bacteria on myelination across multiple brain structures

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Summary

Introduction

Microbial communities in the infant intestine, or the intestinal microbiota, are increasingly considered as a modifiable factor to influence the development of brain and host behavior [1,2,3,4]. Microbiota is acquired around birth and develops to a relative stable community contemporaneously with nervous system development during the first 2–3 years and may have direct and profound impacts on cognition and behavior later in life [5]. Microbiota influence brain development motor activity, anxiety-like behavior and cognitive functions in early childhood as well as the potential pathogenesis of neurodevelopmental disorders, such as autism, attention-deficit/ hyperactivity disorder, and schizophrenia [6,7,8,9,10,11]. Age-related expansion and myelination of the white matter are prominent indictors of brain maturation and cognitive function later in life [18]

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