Disrupted immunometabolism: The hidden culprit behind complex health issues
Nutrition plays a critical role in maintaining a healthy and properly functioning immune system.
The complex relationship between diet, nutrients, and immunity has significant implications for preventing and managing various diseases, from infections to chronic conditions like diabetes and cancer.
Impact of micronutrients on immune function
Micronutrients such as vitamins A, C, D, E, B6, B12, folate, and minerals like zinc, iron, copper, and selenium play vital roles in supporting the immune system at every stage of the immune response[1]. These nutrients help maintain the integrity of physical barriers like skin and mucous membranes, regulate the production of cytokines, and support the function of immune cells such as macrophages, neutrophils, and lymphocytes[2]. Deficiencies in any of these micronutrients can impair various aspects of innate and adaptive immunity, increasing susceptibility to infections and slowing post-infectious recovery[3]. While adequate intake of these nutrients is essential for optimal immune function, daily requirements for optimal immunity are higher than current recommended dietary allowances, especially during periods of increased demand such as infection, stress, or environmental pollution. Supplementation with immune-supporting micronutrients like vitamins C, D, and zinc may help modulate immune function and reduce infection risk, increasingly well-designed clinical studies substantiate these benefits[4].[1]
Role of gut microbiome in immunity
The gut microbiome plays a crucial role in the development and regulation of the immune system. Trillions of microbes reside in the gastrointestinal tract and interact with the mucosal immune system, influencing local and systemic immune responses[5]. The gut microbiota helps train the innate and adaptive immune systems, promotes the development of lymphoid tissues, and regulates the balance between pro-inflammatory and anti-inflammatory responses[6]. Disruptions in the gut microbiome, known as dysbiosis, have been linked to various immune-mediated disorders, including inflammatory bowel disease, coeliac disease, rheumatoid arthritis, and metabolic syndrome[7]. The complex crosstalk between the gut microbiota and the immune system is influenced by diet, antibiotic use, and early life exposures, which can have long-lasting effects on immune function and disease susceptibility [8]. Understanding the intricate interplay between the gut microbiome and immunity may lead to the development of microbiome-targeted interventions for preventing and treating immune-related disorders including immunometabolic dysfunction[9].
Gut microbiota and immune regulation
The gut microbiota regulates the immune system through various mechanisms. The microbes in the gut interact with the intestinal immune cells, influencing their development and function[10]. For example, the gut microbiota can stimulate the production of regulatory T cells (Tregs), from naïve T cells which help maintain immune tolerance and prevent or reverse autoimmunity[11]. The microbiota also promotes the secretion of anti-inflammatory cytokines like IL-10, which help balance the immune response and are essential in preventing immunometabolic disruption.
Additionally, the gut microbiota produces metabolites, such as short-chain fatty acids (SCFAs), that have immunomodulatory effects. SCFAs, particularly butyrate, can enhance the integrity of the intestinal barrier, preventing the translocation of pathogens and reducing inflammation[12]. Furthermore, the gut microbiota competes with pathogens for nutrients and space, helping to prevent their overgrowth and maintaining a healthy balance in the gut. Disruptions in the gut microbiota, known as dysbiosis, can lead to immune dysregulation and contribute to the development of inflammatory, metabolic and autoimmune disorders[13].
Pro-inflammatory vs. anti-inflammatory foods
Certain foods are known to have either pro-inflammatory or anti-inflammatory effects on the body. Pro-inflammatory foods, such as refined and ultra processed carbohydrates, fried foods, sugary beverages, red meat, and processed meats, can trigger the production of inflammatory cytokines and increase the risk of generating and sustaining chronic diseases. In contrast, anti-inflammatory foods, including fruits, vegetables, whole grains, fatty fish, and healthy fats like olive oil, contain nutrients and bioactive compounds that help reduce inflammation[14].
For example, berries, leafy greens, and spices like turmeric are rich in antioxidants and polyphenols that combat oxidative stress and inflammatory processes. Adopting an anti-inflammatory diet, such as the traditional Mediterranean diet, which emphasises these foods while limiting pro-inflammatory ones, can help lower chronic inflammation and reduce the risk of diseases like cardiovascular disease, diabetes, and certain cancers[15].
Dietary fibre and gut health
Dietary fibre which features in the traditional Mediterranean diet plays a crucial role in maintaining gut health by serving as a substrate for the gut microbiota. When fibre reaches the colon, it is fermented by the resident bacteria, producing short-chain fatty acids (SCFAs) like butyrate, propionate, and acetate[16]. These SCFAs have numerous beneficial effects, including providing energy for the colonic epithelial cells, regulating intestinal pH, and promoting the growth of beneficial bacteria like Bifidobacteria and Lactobacilli[17].
Fibre also helps maintain the integrity of the intestinal barrier, preventing the translocation of pathogens and reducing inflammation[18]. Adequate fibre intake (>15gms daily) has been associated with a reduced risk of inflammatory bowel diseases, diverticulitis, and colorectal cancer.
Prebiotic fibres, such as inulin, fructooligosaccharides (FOS), and galactooligosaccharides (GOS), selectively stimulate the growth and activity of beneficial gut bacteria, further promoting gut health. Incorporating a variety of fibre-rich foods, such as fruits, vegetables, whole grains, and legumes, can help support a diverse and resilient gut microbiome, which is essential for optimal digestive and immunometabolic function[19].
Antioxidants and immune defence
Antioxidants play a crucial role in supporting the immune system by neutralising harmful free radicals and reducing oxidative stress. Micronutrients such as vitamins C and E, beta-carotene, and minerals like selenium and zinc are potent antioxidants that enhance various aspects of immune function[20]. These nutrients protect immune cells from oxidative damage, support the production of antibodies and cytokines, and promote the activity of natural killer cells and lymphocytes. Antioxidants also help maintain the integrity of mucous membranes, which serve as a first line of defence against pathogens and pathobionts and may also be helpful in the case of an over-reactive immune response[21],[22].
The impact of processed and ultra-processed foods on immunometabolism and human health
In recent years, the global diet has undergone significant transformations, with processed and ultra-processed foods becoming increasingly prevalent. These foods, characterised by high levels of sugar, unhealthy fats, and additives, have been linked to various chronic health issues[23]. A growing body of research focuses on the mechanisms through which these foods affect our bodies, particularly their impact on immunometabolism, the interplay between immune function and metabolism.
The role of immunometabolism in health and disease
Immunometabolism refers to the metabolic processes that regulate all immune cell function. It plays a crucial role in maintaining homeostasis within the body, responding to infections, and preventing chronic inflammatory conditions. However, disruptions in immunometabolism can lead to various health problems. Research over the past four years has highlighted how processed and ultra-processed foods contribute to such disruptions[24].
Impact on immunometabolism
Studies published during this time have shown that diets rich in processed and ultra-processed foods can significantly alter immunometabolic pathways. High intake of these foods leads to increased inflammation, oxidative stress, and insulin resistance, which are key factors in the development and persistence of chronic diseases. For instance, a study published in Advances in Nutrition in 2024 found that consumption of ultra-processed foods was associated with higher levels of pro-inflammatory cytokines, indicating a shift towards a pro-inflammatory state[25].
Another study in Gut in 2022 demonstrated that ultra-processed foods could disrupt the gut microbiota, leading to imbalances that further exacerbate systemic inflammation and metabolic dysfunction[26]. These findings further underscore the importance of understanding the complex interactions between diet, immunometabolism, and overall health.
Mitigation strategies
To counteract the negative impacts of processed and ultra-processed foods, key strategies have been proposed:
Dietary changes: Incorporating whole foods, such as fruits, vegetables, lean proteins, and whole grains, into the diet can help restore balance to the immune system and improve metabolic health by the ingestion of polyphenols. An excellent study in Frontiers of Immunology in 2024 suggested that a Mediterranean-style diet, rich in polyphenols, antioxidants and omega-3 fatty acids, could effectively reduce systemic inflammation and improve immunometabolic markers[27].
Supplementation: Certain supplements may support immunometabolic health. Vitamin D, for example, has been shown to modulate immune responses and improve metabolic parameters. Similarly, probiotics can help restore a healthy gut microbiota, which is crucial for immunometabolic balance.
Conclusion
The rise of processed and ultra-processed foods poses significant challenges to personal and public health, particularly through its impact on immunometabolism. By understanding the mechanisms through which these foods affect our bodies, we can develop targeted clinical strategies to mitigate their adverse effects. Emphasising whole foods in the diet, alongside strategic supplementation, offers avenues for improving immunometabolic health and reducing the risk of chronic diseases, despite the rapid expansion, driven by the food industry and weak political will to manage food supply, costs and quality.
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