Inflammation: a highly conserved, Janus-like phenomenon—a gastroenterologist’ perspective

Abstract

Inflammation is the result of the loss of host's resilience towards the surrounding world. At gross tissue level, inflammation coincides with fluid leakage from vessels, swelling, and blood stasis and extravasation of mononuclear/macrophage cells. Biochemically, these events lead to anoxia and dramatic changes: interruption of the mitochondrial oxidative phosphorylation, influx of the M1 macrophage subset, which live on anaerobic glycolysis. Fall of ATP then leads to energy shortage and debt. In their chronic forms, these phenomena are now known to mark a number of degenerative disorders that have invaded the Western World since the last century: Parkinson's disease, Alzheimer's syndromes, rheumatic diseases, metabolic diseases. Intriguingly, these affections seem to derive from the gut, along two possible pathways. A sort of ascending loss of function caused by accumulation of (and hyperreactivity to) proteins released to restrain spread of enteric viruses: the alpha-synucleins, now increasingly spotted in relation to Parkinson's pathogenesis. The second pathway would entail the intellectual decline perhaps brought about by large use of food containing the proteins of red processed meat. The bacterium Bilophila wadsworthia, thriving in this meat, can erode the mucus layer on colon surfaces, allowing further bacterial flora to approach lining cells, so upgrading the alarm state. We discuss two strategies to prevent such instability from ending up to full-blown inflammatory bowel disease: physical exercise and systematic switch to fibre-containing diets.

The Role of Succinate in the Regulation of Intestinal Inflammation

“…Paradoxically, although the intestinal mucosa can experience profound hypoxia during chronic inflammation, conditions of inflammation can also result in increased oxygen levels in the intestinal lumen due to increased blood flow (hyperemia) and vascular permeability [62]. This shift in luminal oxygen levels is thought to be one of the mechanisms responsible for the reduction of obligate anaerobes ( Clostridium groups IV or XIVa) and expansion of oxygen-tolerant species including aerobes and facultative anaerobes (Enterobacteriaceae) observed in IBD patients, which could exacerbate dysbiosis and inflammation within the gut [63,64].…”

Dupilumab to target interleukin 4 for inflammatory bowel disease? Hypothesis based on a translational message

“…The intraluminal antigenic stimulation would facilitate the loss of the immunotolerance towards indigenous bacterial flora and consequently activates the gut-associated immune system. 30,31 Pharmacological management of IBD, partly reflects our limited understanding of the pathogenesis of the disease, and its complex phenotypic presentation. [32][33][34][35] IL-4 has also been investigated as a possible pathogenetic factor in the onset of IBD.…”

Pathogenesis of Inflammatory Bowel Disease: Basic Science in the Light of Real-World Epidemiology

“…In our (perhaps biased) opinion, inflammation makes one of these IBD hubs: its place in evolution, its functions, and the mode these functions are exerted support this view: (1) Inflammation is one of the most conserved biological processes [91]; (2) Besides its occasional roles of acute defense, it prevalently acts as a lingering arbiter of the immune dialogues at the barrier gut surface [86]; (3) In its peculiar variant classified as "apoptosis", these functions are paradoxically exerted "in the absence of inflammation" [31], a key pathway to tissue integrity.…”

“…The presence of processed meat and deep-fried cooking used by many city workers coping with nightshifts can favor the intestinal growth of the Bilephila wadsworthi, a pathogen capable to erode intestinal defensins and expose the mucosa to the pro-inflammatory action of further pathogens. We have covered this issue in a recent review [91].…”