Nutritional Components in Western Diet Versus Mediterranean Diet at the Gut Microbiota-Immune System Interplay. Implications for Health and Disease

Abstract

The most prevalent diseases of our time, non-communicable diseases (NCDs) (including obesity, type 2 diabetes, cardiovascular diseases and some types of cancer) are rising worldwide. All of them share the condition of an "inflammatory disorder", with impaired immune functions frequently caused or accompanied by alterations in gut microbiota. These multifactorial maladies also have in common malnutrition related to physiopathology. In this context, diet is the greatest modulator of immune system-microbiota crosstalk, and much interest, and new challenges, are arising in the area of precision nutrition as a way towards treatment and prevention. It is a fact that the westernized diet (WD) is partly responsible for the increased prevalence of NCDs, negatively affecting both gut microbiota and the immune system. Conversely, other nutritional approaches, such as Mediterranean diet (MD), positively influence immune system and gut microbiota, and is proposed not only as a potential tool in the clinical management of different disease conditions, but also for prevention and health promotion globally. Thus, the purpose of this review is to determine the regulatory role of nutritional components of WD and MD in the gut microbiota and immune system interplay, in order to understand, and create awareness of, the influence of diet over both key components.

Keywords: food matrix; gut microbiota; host immunometabolism; immunomodulation; intestinal barrier; malnutrition; mediterranean diet; micronutrients; western diet.

Figure 1

Microbial and eukaryotic components of the gut. As represented in the scheme, gut mucosa is a highly dynamic structure in which microorganisms and epithelial and immune cells are interacting continuously. The gut microbiota is mainly composed of the Firmicutes phylum, followed by Bacteroidetes, Actinobacteria, and other bacteria that are less abundant but equally important, including Proteobacteria and the Verrucomicrobia Akkermansia muciniphilla. Immune detection and response may be assessed at the local Peyer’s patch present in the small intestine, or through mesenteric nodes, activating immune cells and accessing the gut through the bloodstream, finally promoting the release of IgA by plasmatic B cells. Other cells may aid in the capture of microbial antigens, coordinating the immune response, including tuft cells, M cells and even intraepithelial lymphocytes. Paneth cells prominently act through the release of antimicrobial compounds. Enterocytes and globet cells play a key role in maintaining the intestinal barrier, whereas enteroendocrine cells produce certain products that are essential for metabolism and the individual’s health.

Figure 2

Interactions between gut microbiota and immune system. The presence of healthy gut microbiota, their products and metabolites are detected by the different cells located in the gut mucosa. DCs may up-take antigens and present them, as previously commented on, at the Peyer’s patch or mesenteric node, leading to Th naïve differentiation. Certain bacteria such as Alcaligenes may be found in the Peyer’s patch that equally regulate Th fate. Finally, some other bacteria may adhere to the epithelium, promoting the release of cytokines to modulate the immune response. These recognitions are mainly due to Toll-like receptors or Nod-like receptors, leading to inflammasome NLRP3/NLRP6 activation. Then, in gut eubiosis, the activated cells will conduct a proper response, which includes increased mucine production by globet cells, an augmentation of tight junctions by enterocytes, and the secretion of antimicrobial substances by Paneth cells or of IgA by B cells. Likewise, the balance between Treg/Th17 and pro-inflammatory and anti-inflammatory cytokines is vital for the regulation of immune responses, collaborating with an adequate, non-exacerbated response, but also with tolerance. Importantly, under pathological conditions, this balance is lost, and an inflammatory environment is created, contributing to the normal functioning of these cells, along with the associated gut dysbiosis.

Figure 3

A general overview of the main nutritional components modulating both gut microbiota and immune system. As it is represented, the Mediterranean diet, rich in plant-based aliments, presents polyphenols, high-quality fats (MUFAs and high omega 3 PUFAs), micronutrients, such as vitamins and trace elements, and dietary fiber that, in an adequate and complete food matrix, will determine their beneficial properties in maintaining gut microbiota eubiosis and its metabolic products, along with intestinal barrier integrity and immune tolerance. On the other side, western diets and ultra-processed foods, characterized by low levels of dietary fiber or micronutrients, present a plethora of nutritional components, including refined carbohydrates (sugar and refined grains), low-quality fats (trans fatty acids and an excessive omega 6/omega 3 ratio due to the refined oils), salt and unhealthy additives (mainly sweeteners), and finally excessive red and processed meat consumption. Moreover, they comprise a poor food matrix that will have detrimental effects at the intestinal barrier, leading to leaky gut, gut dysbiosis and altered metabolites, further leading to a local inflammation and the presence of LPS in the bloodstream that will contribute to systemic endotoxemia and chronic inflammation.