Transepithelial Effect of Probiotics in a Novel Model of Gut Lumen to Nerve Signaling

Recent studies have shown that the gut microbiome changes brain function, behavior, and psychiatric and neurological disorders. The Gut–Brain Axis (GBA) provides a neuronal pathway to explain this. But exactly how do commensal bacteria signal through the epithelial layer of the large intestine to ac...

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Main Authors: John E. Piletz, Jason Cooper, Kevin Chidester, Kyle Erson, Sydney Melton, Anthony Osemeka, Megan Patterson, Kyndall Strickland, Jing Xuan Wan, Kaitlin Williams
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/14/22/4856
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author John E. Piletz
Jason Cooper
Kevin Chidester
Kyle Erson
Sydney Melton
Anthony Osemeka
Megan Patterson
Kyndall Strickland
Jing Xuan Wan
Kaitlin Williams
author_facet John E. Piletz
Jason Cooper
Kevin Chidester
Kyle Erson
Sydney Melton
Anthony Osemeka
Megan Patterson
Kyndall Strickland
Jing Xuan Wan
Kaitlin Williams
author_sort John E. Piletz
collection DOAJ
description Recent studies have shown that the gut microbiome changes brain function, behavior, and psychiatric and neurological disorders. The Gut–Brain Axis (GBA) provides a neuronal pathway to explain this. But exactly how do commensal bacteria signal through the epithelial layer of the large intestine to activate GBA nerve afferents? An in vitro model is described. We differentiated two human cell lines: <i>Caco2Bbe1</i> into mature epithelium on 0.4-micron filters and then <i>SH-SY5Y</i> into mature neurons in 24-well plates. These were co-cultured by placing the epithelium-laden filters 1 mm above the neurons. Twenty-four hours later they were tri-cultured by apical addition of 10<sup>7</sup><i>Lactobacillus rhamnosus</i> or <i>Lactobacillus fermentum</i> which settled on the epithelium. Alone, the <i>Caco2bbe1</i> cells stimulated neurite outgrowth in underlying <i>SH-SY5Y</i>. Beyond this, the lactobacilli were well tolerated and stimulated further neurite outgrowth by 24 h post-treatment, though not passing through the filters. The results provide face validity for a first-of-kind model of transepithelial intestinal lumen-to nerve signaling. The model displays the tight junctional barrier characteristics found in the large intestine while at the same time translating stimulatory signals from the bacteria through epithelial cells to attracted neurons. The model is easy to set-up with components widely available.
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spelling doaj.art-3800b73d88194ef9ac47b1942ba0cdc82023-11-24T09:32:17ZengMDPI AGNutrients2072-66432022-11-011422485610.3390/nu14224856Transepithelial Effect of Probiotics in a Novel Model of Gut Lumen to Nerve SignalingJohn E. Piletz0Jason Cooper1Kevin Chidester2Kyle Erson3Sydney Melton4Anthony Osemeka5Megan Patterson6Kyndall Strickland7Jing Xuan Wan8Kaitlin Williams9Office of Global Education, Mississippi College, Clinton, MS 39058, USADepartment of Biology, Mississippi College, Clinton, MS 39058, USADepartment of Biology, Mississippi College, Clinton, MS 39058, USADepartment of Biology, Mississippi College, Clinton, MS 39058, USADepartment of Biology, Mississippi College, Clinton, MS 39058, USADepartment of Biology, Mississippi College, Clinton, MS 39058, USADepartment of Biology, Mississippi College, Clinton, MS 39058, USADepartment of Biology, Mississippi College, Clinton, MS 39058, USADepartment of Biology, Mississippi College, Clinton, MS 39058, USADepartment of Biology, Mississippi College, Clinton, MS 39058, USARecent studies have shown that the gut microbiome changes brain function, behavior, and psychiatric and neurological disorders. The Gut–Brain Axis (GBA) provides a neuronal pathway to explain this. But exactly how do commensal bacteria signal through the epithelial layer of the large intestine to activate GBA nerve afferents? An in vitro model is described. We differentiated two human cell lines: <i>Caco2Bbe1</i> into mature epithelium on 0.4-micron filters and then <i>SH-SY5Y</i> into mature neurons in 24-well plates. These were co-cultured by placing the epithelium-laden filters 1 mm above the neurons. Twenty-four hours later they were tri-cultured by apical addition of 10<sup>7</sup><i>Lactobacillus rhamnosus</i> or <i>Lactobacillus fermentum</i> which settled on the epithelium. Alone, the <i>Caco2bbe1</i> cells stimulated neurite outgrowth in underlying <i>SH-SY5Y</i>. Beyond this, the lactobacilli were well tolerated and stimulated further neurite outgrowth by 24 h post-treatment, though not passing through the filters. The results provide face validity for a first-of-kind model of transepithelial intestinal lumen-to nerve signaling. The model displays the tight junctional barrier characteristics found in the large intestine while at the same time translating stimulatory signals from the bacteria through epithelial cells to attracted neurons. The model is easy to set-up with components widely available.https://www.mdpi.com/2072-6643/14/22/4856entericnervous systemcholinergicprobioticsgutbrain
spellingShingle John E. Piletz
Jason Cooper
Kevin Chidester
Kyle Erson
Sydney Melton
Anthony Osemeka
Megan Patterson
Kyndall Strickland
Jing Xuan Wan
Kaitlin Williams
Transepithelial Effect of Probiotics in a Novel Model of Gut Lumen to Nerve Signaling
Nutrients
enteric
nervous system
cholinergic
probiotics
gut
brain
title Transepithelial Effect of Probiotics in a Novel Model of Gut Lumen to Nerve Signaling
title_full Transepithelial Effect of Probiotics in a Novel Model of Gut Lumen to Nerve Signaling
title_fullStr Transepithelial Effect of Probiotics in a Novel Model of Gut Lumen to Nerve Signaling
title_full_unstemmed Transepithelial Effect of Probiotics in a Novel Model of Gut Lumen to Nerve Signaling
title_short Transepithelial Effect of Probiotics in a Novel Model of Gut Lumen to Nerve Signaling
title_sort transepithelial effect of probiotics in a novel model of gut lumen to nerve signaling
topic enteric
nervous system
cholinergic
probiotics
gut
brain
url https://www.mdpi.com/2072-6643/14/22/4856
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