Microbiota driven macrophage mediators in pathogenesis and treatment of
gut leakage: current strategies and future perspectives
- Rani Samsudin,
- Balachandar Selvakumar,
- Priyadharshini Sekar
Abstract
Macrophages play key roles in tissue homeostasis, defense, disease and
repair. Macrophages are highly plastic and exhibit distinct functional
phenotypes based on micro-environmental stimuli. Despite several
advancements in understanding macrophage biology and their different
functional phenotypes in various physiological and pathological
conditions, currently available treatment strategies targeting
macrophages are limited. Macrophages' high plasticity and diverse
functional roles -- including tissue injury and wound healing mechanisms
-- mark them as potential targets to mine for efficient therapeutics to
treat diseases. Despite mounting evidence on association of gut leakage
with several extra-intestinal diseases, there is no targeted standard
therapy to treat gut leakage. Therefore, there is an urgent need to
develop therapeutic strategies to treat this condition. Macrophages are
the cells that play the largest role in interacting with the gut
microbiota in the intestinal compartment and exert their intended
functions in injury and repair mechanisms. In this review, we have
summarized the current knowledge on the origins and phenotypes of
macrophages. The specific role of macrophages in intestinal barrier
function, their role in tissue repair mechanisms and their association
with gut microbiota are discussed. In addition, currently available
therapies and the putative tissue repair mediators of macrophages for
treating microbiota dysbiosis induced gut leakage are also discussed.
The overall aim of this review is to convey the intense need to screen
for microbiota induced macrophage-released pro-repair mediators, which
could lead to the identification of potential candidates that could be
developed for treating the leaky gut and associated diseases.