The stress polarity signaling (SPS) pathway serves as a marker and a target in
the leaky gut barrier: implications in aging and cancer.
Authors Ghosh P, Swanson L, Sayed IM, Mittal Y, Lim BB, Ibeawuchi SR, Foretz M, Viollet
B, Sahoo D, Das S
Submitted By Soumita Das on 3/18/2020
Status Published
Journal Life science alliance
Year 2020
Date Published 3/1/2020
Volume : Pages 3 : Not Specified
PubMed Reference 32041849
Abstract The gut barrier separates trillions of microbes from the largest immune system
in the body; when compromised, a "leaky" gut barrier fuels systemic
inflammation, which hastens the progression of chronic diseases. Strategies to
detect and repair the leaky gut barrier remain urgent and unmet needs. Recently,
a stress-polarity signaling (SPS) pathway has been described in which the
metabolic sensor, AMP-kinase acts via its effector, GIV (also known as Girdin)
to augment epithelial polarity exclusively under energetic stress and suppresses
tumor formation. Using murine and human colon-derived organoids, and
enteroid-derived monolayers (EDMs) that are exposed to stressors, we reveal that
the SPS-pathway is active in the intestinal epithelium and requires a
catalytically active AMP-kinase. Its pharmacologic augmentation resists
stress-induced collapse of the epithelium when challenged with microbes or
microbial products. In addition, the SPS-pathway is suppressed in the aging gut,
and its reactivation in enteroid-derived monolayers reverses aging-associated
inflammation and loss of barrier function. It is also silenced during
progression of colorectal cancers. These findings reveal the importance of the
SPS-pathway in the gut and highlights its therapeutic potential for treating gut
barrier dysfunction in aging, cancer, and dysbiosis.

Investigators with authorship
Soumita DasUniversity of California San Diego