Salicylates and the Microbiota: A New Mechanistic Understanding of an Ancient Drug's Role in Dermatological and Gastrointestinal Disease

Abstract

The proposed mechanism(s) of action of salicylates are as varied as their extraordinary range of clinical indications. Extracted from plant leaves since the beginning of recorded history, salicylates have been used for over 4000 years for the treatment of disease. The anti-inflammatory and antiplatelet agent aspirin (acetylsalicylic acid) was synthesized at the turn of the 20th century and paved the way for salicylates becoming the most widely used drug in the world. Its parent compound salicylic acid as well as the derivatives bismuth subsalicylate and 5-aminosalicylate are invaluable topical treatments for many dermatological and gastrological diseases. Their mode of action is poorly understood, but a developing understanding of the role of the microbiota in diseases of the skin and intestine suggest microbial targets as a possible unifying mechanism. There is a relatively substantial and little-known literature demonstrating the antibiofilm and antibiotic-metabolizing effects of salicylates. A better understanding of this antimicrobial mechanism in dermatological and gastrointestinal diseases could lead to new adjunctive treatments aimed at modulating microbes rather than host inflammation. Drug Dev Res 74 : 344-352, 2013.

In Silico Comparison Shows that the Pan-Genome of a Dairy-Related Bacterial Culture Collection Covers Most Reactions Annotated to Human Microbiomes

“…However, salicylates can also activate the AhR [ 56 ], which is involved in cellular proliferation and differentiation and has a major role in adaptive and innate immune response [ 57 ]. Furthermore, salicylates influence the intestinal microbiome itself by decreasing the expression of adherence factors and biofilm formation [ 58 ]. The degradation of salicylates therefore contributes to the salicylate homeostasis and thus influences different biological functions regulated by AMPK and AhR activation, as well as the composition and structure of the intestinal microbiome.…”

The intestinal microbiome, barrier function, and immune system in inflammatory bowel disease: a tripartite pathophysiological circuit with implications for new therapeutic directions

“…Mesalamine and other salicylates for example have been shown to change the intestinal microbiota and this may in part be due to direct effects on microbes [Andrews et al 2011]. Indeed, mesalamine and other salicyaltes decrease the expression of microbial adherence factors and biofilm formation [Damman, 2013]. Unlike immunomodulators, which lead to proliferation of mucosally associated bacteria, mesalamine leads to a decrease in mucosally associated bacteria in UC [Swidsinski et al 2007].…”

Antimicrobial and antioxidant activity of Evernia prunastri extracts and their isolates

“…org/). Salicylates have been shown to possess antibiofilm and anti-metabolic effects on bacteria (Damman 2013).…”

“…The scaffold of evernic acid is phenyl salicylate (ZINC, http://zinc.docking.org/ ). Salicylates have been shown to possess antibiofilm and anti-metabolic effects on bacteria (Damman 2013 ).…”