Abstract
Antibiotic use during adolescence may result in dysbiosis-induced neuronal vulnerability both in the enteric nervous system (ENS) and central nervous system (CNS) contributing to the onset of chronic gastrointestinal disorders, such as irritable bowel syndrome (IBS), showing significant psychiatric comorbidity. Intestinal microbiota alterations during adolescence influence the expression of molecular factors involved in neuronal development in both the ENS and CNS. In this study, we have evaluated the expression of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase B (TrkB) in juvenile mice ENS and CNS, after a 2-week antibiotic (ABX) treatment. In both mucosa and mucosa-deprived whole-wall small intestine segments of ABX-treated animals, BDNF and TrKB mRNA and protein levels significantly increased. In longitudinal muscle-myenteric plexus preparations of ABX-treated mice the percentage of myenteric neurons staining for BDNF and TrkB was significantly higher than in controls. After ABX treatment, a consistent population of BDNF- and TrkB-immunoreactive neurons costained with SP and CGRP, suggesting up-regulation of BDNF signaling in both motor and sensory myenteric neurons. BDNF and TrkB protein levels were downregulated in the hippocampus and remained unchanged in the prefrontal cortex of ABX-treated animals. Immunostaining for BDNF and TrkB decreased in the hippocampus CA3 and dentate gyrus subregions, respectively, and remained unchanged in the prefrontal cortex. These data suggest that dysbiosis differentially influences the expression of BDNF-TrkB in the juvenile mice ENS and CNS. Such changes may potentially contribute later to the development of functional gut disorders, such as IBS, showing psychiatric comorbidity.
Highlights
Numerous studies have established that the naturally occurring commensal microbiota, which in the human gut is composed of about 3.8X 1013 bacterial cells belonging to approximately 2000 species, represents an essential organ for the host homeostasis by contributing to the metabolism of nutrients, development of the immune host defence and maturation of the gastrointestinal (GI) tract [1]
brain-derived neurotrophic factor (BDNF) immunoreactivity was found in prolongations discontinuously surrounding neurons, in interconnecting strands between ganglia and in bundles of fibers running along the longitudinal smooth muscle (Fig 2 panels A-C and D-F)
A significant (p
Summary
Numerous studies have established that the naturally occurring commensal microbiota, which in the human gut is composed of about 3.8X 1013 bacterial cells belonging to approximately 2000 species, represents an essential organ for the host homeostasis by contributing to the metabolism of nutrients, development of the immune host defence and maturation of the gastrointestinal (GI) tract [1]. Environmental insults, such as the use of antibiotics, stress, harmful events and poor diet, may result in dysbiosis-induced neuronal vulnerability both in the ENS and CNS This neuronal susceptibility to microbiota alterations contributes to the onset of chronic functional GI disorders, such as irritable bowel syndrome (IBS), which is associated with psychological distress and psychiatric comorbidity, including depression [9, 13]. From this perspective, it is important to evaluate whether changes in the symbiotic microbial flora during adolescence may influence the expression of some factors involved in neuronal development and plasticity both in the ENS and CNS. BDNF represents a neurotransmitter/neuromodulator in enteric neuronal circuitries, favouring the local release of enteroendocrine molecules and neurotransmitters from sensory and motor neurons, enhancing peristalsis and gut motility both in laboratory animals and in humans [23,24,27,28]
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