NSAID-enteropathy and intestinal microbes
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Inflammopharmacology
EDITORIAL
NSAID‑enteropathy and intestinal microbes Ingvar Bjarnason1 · K. D. Rainsford2 Received: 25 September 2020 / Accepted: 26 September 2020 © Springer Nature Switzerland AG 2020
Keywords NSAID · Enteropathy · Small bowel damage · Intestinal microbiome · Pathogenesis of NSAID-enteropathy It is ironic as the financial support for research into the gastrointestinal side effects of NSAIDs has declined with a noticeable decrease in the number of original research studies being published that the pathogenesis and pathophysiological effects of NSAIDs are now increasingly understood. Independent research workers have formulated a comprehensive framework for the gastrointestinal damage, largely based on “older” studies that the more forceful “opinion leaders” at the time ignored in their persistent, single minded attempt to keep the message simple, namely the misleading message that Cox-1 and Cox-2 inhibition accounts for all the side effects and therapeutic effects of NSAIDs, respectively. This view was largely market driven, simple and easily understood which is important for the uninitiated prescribers. It is, however, an important reminder that much of what is accepted in science is still personality driven and the facts are not widely voiced until the “opinion leaders” retire from the field. Big Pharma, their servants and collaborators highlighted the gastric side effects, at the exclusion of other gastrointestinal sites, because of the potential use of their drugs that could prevent and treat the gastro-duodenal side effects alone. Nevertheless, the adverse effects of NSAIDs were much more prevalent in the small bowel that the stomach (Bjarnason et al. 1993) and the pathogenesis much more interesting (Bjarnason et al. 2018). There is now an acknowledgement that the pathogenesis of NSAID-induced gastrointestinal damage is far more complex than simply the inhibition of COX-1 and 2. Indeed, neither mechanism plays a major part in initiating the damage. A recently proposed framework for the damage (Bjarnason * Ingvar Bjarnason [email protected] 1
Department of Gastroenterology, King’s College Hospital, Denmark Hill, London SE5 9RS, UK
Biomedical Research Centre, Sheffield Hallam University, Sheffield S11WB, UK
2
et al. 2018) can be summarised as a multi-stage pathogenic process and this involves an initial effect on mitochondria. Hence all acidic, and to a lesser extent basic COX-2 inhibitors initiate damage by a “topical” effect which involves a “detergent” action on the surface cellular phospholipids and more importantly uncoupling of mitochondrial oxidative phosphorylation following their entry into the surface cells. This, in turn, renders the intestinal cells deficient in energy sources (ATP) with predictable cellular-tissue consequences, including activation of caspases and increased mucosal permeability. At this stage, reduced levels of mucosal and circulating prostanoids, from inhibition of COX-1 and 2, plays a permissive role in modifying the cellular-tissue respons
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