NONSTEROIDAL ANTI-INFLAMMATORY DRUGS AS THERAPEUTIC ALLIES OF THE GUT MICROBIOME ON CHRONIC INFLAMMATION

Abstract

Our gut harbours around 1014 bacteria of more than 1000 species, accounting for approximately 2 kg of biomass. The gut microbiome plays several vital functions in processes such as the development of the immune system, food digestion and protection against pathogens. For these functions to be beneficial for both host and microbiome, interactions are tightly regulated. Gut and immune cells continuously interact to distinguish among commensal microbiota, harmless foodstuff, and pathogens. A fine balance between inflammatory and anti-inflammatory state is fundamental to protect intestinal homeostasis. Nonsteroidal anti-inflammatories (NSAIDs) are a class of drugs used for management of pain and inflammation. These compounds have heterologous structures but similar therapeutic activities. The target of all NSAIDs are the isoforms of cyclooxygenase enzymes (COX): the primarily constitutive form COX-1, and the inducible from COX-2. Both isoforms catalyse the conversion of arachidonic acid to PGH2, the immediate substrate for specific prostaglandin and thromboxane synthesis. The gut microbiota plays a role in drug metabolism,  resulting in altered bioavailability of these compounds. Additionally, complex host-microbiome interactions lead to modified xenobiotic metabolism and altered expression of genes involved in drug metabolism. These effects can be at gut tissue-level, or distant, including in the liver. Besides the gut microbiome influencing drug metabolism, drugs also impact the microbial communities in the gut. As different drugs exert selective pressures on the gut microbiome,  understanding this bidirectional relationship is crucial for developing effective therapies for managing chronic inflammation.