The generation of molecular defences to trigger and sustain the production of metabolic inflammatory episodes driven by Western lifestyles appear to create an immune programming capability.
What does that mean? Our innate immune system, the one we are born with and which is not meant to have any related memory capabilities can it seems, be imprinted with patterns that retain activation after the trigger has been resolved. A challenge that may require immune resetting along with dietary and lifestyle changes to generate resolution.
As we all know, and increasingly it seems many of our enlightened medical colleagues are discovering that the key risk factor for the development and sustaining of metabolic diseases is the Western diet. Typically described as high in calories and rich in sugars, trans and saturated fats, salt and food additives, but low in complex carbohydrates, fibre, vitamins and minerals.
Recently and rather depressingly research has demonstrated that for the first time ever, life expectancy is projected to decline and It is likely that this downward trend will accelerate as a result of the detrimental effects of the Western lifestyle on the health of the current generation of children. Hence, the extension of a healthy life by the promotion of effective preventive measures as well as novel treatments for non-communicable diseases should be key goals of your health creation efforts.
Studies establishing that there is a causative relationship via the generation and sustaining of an inflammatory response show that the consumption of a Western diet leads to both quantitative and qualitative changes in intestinal commensal bacteria communities (dysbiosis) and the metabolites they produce.
Then they confirm that Western diet consumption disturbs the gut barrier integrity, which — together with dysbiosis — promotes the influx of harmful microbial products into the portal vein circulation and the induction of systemic inflammation. In addition, this increased permeability disturbs local immune cell signalling, causes an influx of inflammatory myeloid cells and promotes a switch of gut-resident macrophages from a tolerogenic to an inflammatory state and results in a reduction of beneficial regulatory T cells, that mediate inflammatory responses.
Importantly, the Western diet-induced systemic inflammation and reprogramming of myeloid cell precursors was mediated through activation of the NLRP3 inflammasome, which is a key innate immune sensor for many environmental danger signals, such as uric acid, ATP, oxidised mitochondrial DNA and cholesterol crystals. The Western diet triggered an increase in myelopoiesis and induced trained immunity in both differentiated myeloid cells and myeloid precursor cells. In effect, the Western diet appears to be mistakenly recognised by the immune system as a threat to the organism and a memory against its presence is developed responding in an adapted, typically sensitised, manner upon re-exposure.
Whilst these proposals will need to be demonstrated in human clinical studies there is a clear link between the Western diet and the induction and maintenance of tissue inflammation driven by immune interaction. With most of the world’s population living in areas where being overweight is responsible for more deaths than being underweight and with more than one-third of adults worldwide classified as overweight or obese, we face a pandemic of lifestyle-associated diseases.
Tackling lifestyle induced metainflammation diseases requires multimodal interventions, as prevention and restitution have similar mechanistic pathways that need to be reprogrammed or programmed to induce tolerance and immune competence without excess reactivity. Food represents one of the primary paths for clinicians and practitioners to focus on, as it has been highjacked by the food industry, but stress, activity, sleep, behavioural habits and environmental exposures are also key to resolve.