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Neuroscience/Nutrition and the Brain (Poster Session)

(P25-005-24) Effects of Short Chain Fatty Acids on Growth Factor and Pro-inflammatory Cytokine Production in Enteric Glial Cells

Monday, July 1, 2024
11:45 AM – 12:45 PM CT
Location: Poster Board 459
Disclosure(s):
Michelle Beltran, BSc: No relevant financial relationship(s) with ineligible companies to disclose.
Danielle M. Defries, MSc, PhD: No relevant financial relationship(s) with ineligible companies to disclose.


Objectives: Enteric glial cells (EGCs), the major cell type in the enteric nervous system, are involved in intestinal homeostasis by secreting growth factors that attenuate intestinal inflammation and enhance the intestinal epithelial barrier. However, when exposed to chronic inflammatory conditions, EGCs secrete proinflammatory cytokines detrimental to the intestinal barrier. Recently, butyrate a short chain fatty acid (SCFA) characterized as a histone deacetylase (HDAC) inhibitor, has been shown to increase expression of barrier-enhancing growth factors and reduce proinflammatory cytokines in many intestinal cell types. However, it remains unknown if SCFAs affect EGCs. This study aims to investigate: (1) if treating EGCs with SCFAs influences production of growth factors; (2) whether SCFAs alter proinflammatory cytokine production in EGCs.

Methods: The established enteroglial cell line (CR2690) was treated with butyrate (0-10mM), propionate (0-10mM) or pharmacological HDAC inhibitors SAHA or TSA (0.1µM-10µM) for 8h-72h with or without IFNɣ (0-10µg/mL) to activate EGCs. Changes in proinflammatory cytokines (IL6, IL-1β, and TNFα) and growth factors (GDNF & TGF-b1) in EGCs was assessed using Western blotting.

Results: SCFAs reduced GDNF in EGCs but did not reach statistical significance. However, SCFAs significantly decreased TGF-β1 in EGCs (P < 0.05). TSA decreased GDNF and TGF-β1 in EGCs but not statistically significant. SAHA significantly decreased GDNF and TGF-β1 in EGCs (P < 0.05), suggesting that SCFAs intracellular effects in EGCs are analogous to pharmacological HDAC inhibitors. No significant difference was observed in IL6, IL-1b, or TNFα in activated EGCs in response to SCFAs. Interestingly, butyrate significantly increased IL-1b and TNFα in non-activated EGCs (P < 0.05), suggesting that SCFAs facilitate inflammatory effects in EGCs.

Conclusions: SCFAs directly decrease barrier-enhancing growth factors and increase proinflammatory cytokines in EGCs, which may indirectly have detrimental effects on the intestinal barrier.

Funding Sources: University of Winnipeg Major Research Grant