Intestinal barrier dysfunction orchestrates onset of inflammatory host–microbiome cross-talk in a human gut inflammation-on-a-chip, 2018, Shin and Kim

Andy · Nov 1, 2018

Abstract
The initiation of intestinal inflammation involves complex intercellular cross-talk of inflammatory cells, including the epithelial and immune cells, and the gut microbiome. This multicellular complexity has hampered the identification of the trigger that orchestrates the onset of intestinal inflammation.

To identify the initiator of inflammatory host–microbiome cross-talk, we leveraged a pathomimetic “gut inflammation-on-a-chip” undergoing physiological flow and motions that recapitulates the pathophysiology of dextran sodium sulfate (DSS)-induced inflammation in murine models. DSS treatment significantly impaired, without cytotoxic damage, epithelial barrier integrity, villous microarchitecture, and mucus production, which were rapidly recovered after cessation of DSS treatment.

We found that the direct contact of DSS-sensitized epithelium and immune cells elevates oxidative stress, in which the luminal microbial stimulation elicited the production of inflammatory cytokines and immune cell recruitment. In contrast, an intact intestinal barrier successfully suppressed oxidative stress and inflammatory cytokine production against the physiological level of lipopolysaccharide or nonpathogenic Escherichia coli in the presence of immune elements. Probiotic treatment effectively reduced the oxidative stress, but it failed to ameliorate the epithelial barrier dysfunction and proinflammatory response when the probiotic administration happened after the DSS-induced barrier disruption.

Maintenance of epithelial barrier function was necessary and sufficient to control the physiological oxidative stress and proinflammatory cascades, suggesting that “good fences make good neighbors.” Thus, the modular gut inflammation-on-a-chip identifies the mechanistic contribution of barrier dysfunction mediated by intercellular host–microbiome cross-talk to the onset of intestinal inflammation.
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Paywalled at http://www.pnas.org/content/early/2018/10/18/1810819115

Blog from Jackson Labs about the study

A new study in PNAS has linked the interaction between the intestinal epithelial barrier, the gut microbiome, and immune cells to intestinal inflammation. It is thought that the gut microbiota and immune cells contribute to gut inflammation, but until now, it has been difficult to identify exactly what triggers the onset of intestinal inflammation due to the complexity of the cross-talk between the multiple different cell types.
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https://jaxmecfs.com/2018/11/01/gut...arrier-disruption-initiates-gut-inflammation/

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Intestinal barrier dysfunction orchestrates onset of inflammatory host–microbiome cross-talk in a human gut inflammation-on-a-chip, 2018, Shin and Kim

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Intestinal barrier dysfunction orchestrates onset of inflammatory host–microbiome cross-talk in a human gut inflammation-on-a-chip, 2018, Shin and Kim

Andy Committee Member

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