Influence of bacterial components on the developmental programming of enteric neurons

• Published in: Physiological reports 2020-11, Vol.8 (21), p.e14611-n/a
• Main Authors: Popov, Jelena, Bandura, Julia, Markovic, Filip, Borojevic, Rajka, Anipindi, Varun C., Pai, Nikhil, Ratcliffe, Elyanne M.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Apoptosis; Bacteria; Bacteria - metabolism; bacterial components; Cell Differentiation - physiology; Cell proliferation; Cells, Cultured; Colonization; development; Dopamine receptors; Embryos; Enteric nervous system; Enteric Nervous System - cytology; Enteric Nervous System - metabolism; Enteric Nervous System - microbiology; enteric neural crest‐derived cells; Female; Fetuses; Flagellin; Interfaces; Intestine; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Microbiota; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neural crest; Neural stem cells; Neurons; Neurons - cytology; Neurons - metabolism; Neurons - microbiology; Original Research; Peptidoglycans; Physiology; Pregnancy; Serotonin
• ISSN: 2051-817X
• DOI: 10.14814/phy2.14611

Background Intestinal bacteria have been increasingly shown to be involved in early postnatal development. Previous work has shown that intestinal bacteria are necessary for the structural development and intrinsic function of the enteric nervous system in early postnatal life. Furthermore, colonization with a limited number of bacteria appears to be sufficient for the formation of a normal enteric nervous system. We tested the hypothesis that common bacterial components could influence the programming of developing enteric neurons. Methods The developmental programming of enteric neurons was studied by isolating enteric neural crest‐derived cells from the fetal gut of C57Bl/6 mice at embryonic day 15.5. After the establishment of the cell line, cultured enteric neuronal precursors were exposed to increasing concentrations of a panel of bacterial components including lipopolysaccharide, flagellin, and components of peptidoglycan. Key Result Exposure to bacterial components consistently affected proportions of enteric neuronal precursors that developed into nitrergic neurons. Furthermore, flagellin and D‐gamma‐Glu‐mDAP were found to promote the development of serotonergic neurons. Proportions of dopaminergic neurons remained unchanged. Proliferation of neuronal precursor cells was significantly increased upon exposure to lipopolysaccharide and flagellin, while no significant changes were observed in the proportion of apoptotic neuronal precursors compared to baseline with exposure to any bacterial component. Conclusions and Interfaces These findings suggest that bacterial components may influence the development of enteric neurons. Exposure to flagellin and D‐gamma‐Glu‐mDAP affected the proportion of enteric neuronal precursors that developed into serotonergic neurons. Nitrergic neuron development was influenced by exposure to lipopolysaccharide, flagellin, muramyl dipeptide, and D‐gamma‐Glu‐mDAP, while proportions of dopaminergic neurons remained unchanged. Proliferation of neuronal precursor cells was influenced by lipopolysaccharide and flagellin, while apotosis remained unaffected by exposure to each of the bacterial components.