Gut-Liver Physiomimetics Reveal Paradoxical Modulation of IBD-Related Inflammation by Short-Chain Fatty Acids
Name
706812v2.full.pdf
Description
Submitted version
Size
11.51 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Trapecar, Martin
Communal, Catherine
Velazquez, Jason G
Maass, Christian Alexander
Huang, Yu-Ja
Schneider, Kirsten
Wright, Charles
Butty, Vincent L G
Eng, George M.
Yilmaz, Omer
Date Issued
March 2020
Journal
Cell Systems
Publisher
Elsevier BV
Citation
Trapecar, Martin et al. "Gut-Liver Physiomimetics Reveal Paradoxical Modulation of IBD-Related Inflammation by Short-Chain Fatty Acids." Cell Systems 10, 3 (March 2020): P223-239.E9 © 2020 Elsevier Inc
Version
Original manuscript
Abstract
Although the association between the microbiome and IBD and liver diseases is known, the cause and effect remain elusive. By connecting human microphysiological systems of the gut, liver, and circulating Treg and Th17 cells, we created a multi-organ model of ulcerative colitis (UC) ex vivo. The approach shows microbiome-derived short-chain fatty acids (SCFAs) to either improve or worsen UC severity, depending on the involvement of effector CD4 T cells. Using multiomics, we found SCFAs increased production of ketone bodies, glycolysis, and lipogenesis, while markedly reducing innate immune activation of the UC gut. However, during acute T cell-mediated inflammation, SCFAs exacerbated CD4+ T cell-effector function, partially through metabolic reprograming, leading to gut barrier disruption and hepatic injury. These paradoxical findings underscore the emerging utility of human physiomimetic technology in combination with systems immunology to study causality and the fundamental entanglement of immunity, metabolism, and tissue homeostasis.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
Massachusetts Institute of Technology. Research Laboratory of Electronics
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.cels.2020.02.008
