Insights into the immunological links between dietary habits and asthma

KEYWORDS:

• Asthma
• immunity
• diet
• trained immunity
• immunometabolism

1. Introduction

Asthma is a chronic respiratory condition characterized by breathing difficulties due to inflammation and narrowing of the bronchial passages [1]. Excessive mucus production further exacerbates these breathing challenges [1]. Allergic asthma can be triggered by inhaling allergens like pollen or dust, while non-allergic variants are associated with factors such as obesity, exposure to tobacco smoke, and certain medications, including nonsteroidal anti-inflammatory drugs (NSAIDs) [1].

Globally, asthma affects an estimated 339 million people, and its prevalence is on the rise [2]. It stands as the leading noninfectious disease in children and remains one of the most common chronic conditions in adults. In 2017, asthma was responsible for approximately 495,100 deaths worldwide [2].

In terms of dietary habits and their potential immunological links to asthma, this editorial delves deeply into their complex relationship. Drawing on recent research findings, we aim to determine whether diet changes can modulate the immune system and, in turn, influence the clinical manifestations of asthma.

1.1. Current evidence of relationship between dietary habits, immunity, and asthma

The choices we make in our daily lives, particularly in terms of our dietary habits, play a pivotal role in shaping our overall health. One of the most profound impacts of these choices is observed in the modulation of our immune system.

1.2. The gut, immunity, and asthma

The gastrointestinal tract, often called the ‘second brain,’ contains a microbiome significantly influenced by diet. An overall healthy diet, which includes fiber-rich and fermented foods are central to shaping this microbial composition [3]. A balanced gut produces anti-inflammatory short-chain fatty acids (SCFAs) like butyrate, strengthening the gut’s defenses. Diet not only regulates the microbiome but also directly affects immune responses [4]. While healthy diet support beneficial bacteria, processed foods can reduce microbial diversity, increasing the risk of conditions like asthma. Early dietary choices, from breastfeeding duration to introducing allergenic foods, can influence asthma risk in children [4].

Several studies linked some dietary habits with a higher prevalence of wheezing or asthma [5,6]. A recent study using an OVA/poly I:C-induced asthma model revealed a strong gut-lung connection, suggesting potential therapeutic avenues through gut microbial metabolism [4]. Another study explored the link between microbial imbalances in the airways and gut concerning childhood asthma, emphasizing the combined effects of environment, host responses, and microbial diversity [7]. Studies on infants suggest their gut microbiome composition can predict asthma risk, with factors like delivery method and feeding practices being influential [7]. Additionally, research on the traditional Chinese remedy, You-Gui-Wan, showed its benefits in treating dust mite-induced allergic asthma in mice, reinforcing the importance of the gut-lung axis in asthma treatment [8].

Recent studies unveil a distinct microbial and metabolic profile in non-allergic asthmatics, showcasing a unique microbiome influence [9]. Long-recognized dietary imbalances such as obesity or micronutrient deficiencies are posited as potential exacerbators of asthma symptoms and allergy susceptibility. The starkly contrasting microbial and metabolic landscapes between allergic and non-allergic asthma underscore the microbiome’s pivotal role in modulating asthma phenotypes. Moreover, food additives have been implicated in triggering non-allergic asthma symptoms, hinting at a nuanced dietary influence on non-allergic conditions compared to allergic ones. These insights accentuate the imperative of delving deeper into the relationship between diet, microbiome, and asthma.

1.3. Dietary components and systemic inflammation

Asthma, particularly its neutrophilic inflammatory phenotype, the non-allergic type, is often associated with systemic inflammation. Diets rich in saturated fats, trans fats, and sugars can induce a state of low-grade systemic inflammation, characterized by the release of pro-inflammatory cytokines [10]. This chronic inflammation, over time, can impair immune functionality. The Western diet, known for its low antioxidant content and high levels of saturated fatty acids, is thought to create a pro-inflammatory environment. These fatty acids can stimulate innate immune responses by activating receptors such as toll-like receptor 4 (TLR4), which subsequently triggers the NF-κB inflammatory pathway [11].

In contrast, the Mediterranean diet (Med-diet), abundant in omega-3 fatty acids, polyphenols, and antioxidants, serves as a protective barrier against inflammation. A recent meta-analysis emphasized its anti-inflammatory effects, showing significant reductions in plasma CRP levels, IL-6 production, and intracellular adhesion molecule-1 (ICAM-1) among those adhering to this diet [12]. Both human and animal studies have shown that regular fish consumption can mitigate chronic inflammatory conditions. Specifically, omega-3 fatty acids have been found to counteract pathophysiological processes associated with asthma [13].

Recent research explored the effect of Omega-3 polyunsaturated fatty acids (n-3 PUFAs) on inflammation reactions. While n-3 PUFAs can be helpful for cardiovascular disease and obesity, their impact on asthma remains uncertain. According to this study, diet containing n-3 PUFAs was shown to alter pulmonary sphingolipid composition resulting in hyperreactivity without the presence of inflammation [14].

Several studies reported a more consistent association between diet and pediatric asthma, especially regarding maternal and early childhood diet, compared to adult asthma. A recent systematic review indicated that adherence to a Mediterranean diet, rich in fruits and vegetables, is associated with better asthma outcomes in children [15]. Conversely, a Western diet, high in processed foods and low in fruits and vegetables, is linked to increased asthma risk in adults [16]. Other studies are exploring dietary intake and asthma across ages, with some evidence suggesting dietary patterns can influence asthma risk and management, warranting further investigation to develop dietary guidelines for asthma prevention and treatment [17].

The 2014 study by Trompette et al. [18] addressed how dietary fiber content impacts intestinal microbiota, and subsequently, the production of short-chain fatty acids (SCFAs) such as propionate and acetate. The authors found that mice fed diets rich in fermentable fibers exhibited a better response to influenza infection by effectively modulating immune response systems – notably enhancing antiviral CD8+ T cell responses while mitigating harmful immunopathology triggered by neutrophils. In a 2021 study, Ubags et al. [19] investigated the connection between microbiome-induced antigen-presenting cell recruitment to both skin and lung inflammation, thereby enriching the understanding of its role in allergic asthma pathogenesis. Although this work did not directly address dietary components, it provided valuable insight into the microbiome’s interaction with allergic asthma pathogenesis [19].

Castan et al.‘s 2018 [20]probed the mechanisms underpinning the atopic march, or the progression from food and cutaneous allergies to rhinitis and asthma, through food allergen-sensitized CCR9+ lymphocytes intensifying allergy inflammation in the airways. This highlighted multi-organ involvement as well as the potential role of chemokines and their receptors in its progression. The research elucidated how the gut-lung axis theory may contribute to both asthma and food allergies, reinforcing the trained immunity theory with respect to food allergies that developed through this theoretical framework [20].

However, the assessment of diet and nutrient content of foods entails multiple challenges, including recall bias from self-reported intake data, and variations in nutrient composition due to differing food preparation and cooking methods. Additionally, the diversity in individual diets and the lack of standardization in assessment methods impede accurate data collection, rendering comparisons between studies challenging. Conducting comprehensive dietary assessments necessitates resource-intensive tools and trained personnel, which may deter larger or longer-term studies from undertaking such thorough assessments.

1.4. Immunometabolic pathways in asthma

Recent studies have shown that in asthmatic individuals, immune cells display heightened oxidative stress due to abnormal metabolic activities. This oxidative stress, resulting from an imbalance between free radical production and the body’s antioxidative defenses, can initiate cell apoptosis and activate crucial immune signaling pathways [21]. When disrupted, these pathways can exacerbate asthma. Diet plays a pivotal role in this context. For instance, L-carnitine metabolism, mainly from red meat, leads to trimethylamine N-oxide (TMAO) production, which, when elevated, can amplify inflammatory responses and worsen asthma symptoms. On the other hand, antioxidant-rich diets, rich in fruits, vegetables, and certain oils, can counteract oxidative stress, potentially reducing asthma’s impact [22]. Additionally, dietary patterns influence cellular autophagy, essential for pathogen clearance and antigen presentation, thereby supporting immune balance. However, the complete understanding of asthma’s immunometabolism remains an area of ongoing research.

1.5. Trained immunity, asthma, and diet

Trained immunity, or ‘innate memory,’ describes the enhanced response of innate immune cells to subsequent unrelated challenges after an initial exposure to an infectious or inflammatory agent [23]. While beneficial against infections, it can also influence the pathogenesis of ailments like fatty liver diseases [24], gut inflammation [25], and endotoxemia [26], potentially exacerbating other inflammatory diseases. For example, in NSAID-exacerbated respiratory disease (N-ERD), there is evidence of heightened inflammatory responses in monocyte-derived macrophages (MDM) due to reduced gene methylation, suggesting an ‘inflammatory memory’ [27]. Another study on house dust mite (HDM)-allergic asthma patients revealed similar inflammatory imprints in MDMs, influenced by factors like TNF production and metabolic shifts [28]. The exact mechanisms and long-term implications of this reprogramming in asthma remain areas of active investigation.

1.6. Expert opinion

Asthma is a chronic respiratory ailment affecting millions worldwide, necessitating a deeper understanding of its triggers and modulators. In this editorial, we investigate the intricate relationship between diet, immunity, and asthma

Our understanding of how diet influences immune responses has expanded considerably, yielding insights such as the gut-lung axis and its potential therapeutic relevance for asthma. We possess substantial knowledge about the influence of our consumption choices on systemic inflammation, from the pro-inflammatory Western diets to the anti-inflammatory Mediterranean diet. However, the evidence surrounding relationship between these diets, immunity and specific asthma phenotypes remains in its nascent stages and still awaits full elucidation. Further, data on Western and Mediterranean diets are taken from observational studies not randomized controlled trials.

Dietary interventions present a promising non-pharmacological therapeutic approach for asthma. We envision precision nutrition as personalized dietary guidance tailored to an individual’s asthma subtype, gut microbiome composition, and genetic makeup. This could not only mitigate asthma flare-ups but also reduce reliance on pharmacological interventions.

Additionally, Obesity plays a pivotal role in both allergic and non-allergic asthma, albeit via distinct mechanisms. In allergic asthma, obesity seems to intensify the allergic inflammatory response, likely due to adipose tissue releasing pro-inflammatory cytokines that exacerbate airway inflammation. Contrarily, in non-allergic asthma, especially the neutrophilic forms, obesity doesn’t intensify but might mitigate the allergic inflammatory response by releasing cytokines from fat cells that temper airway inflammation. Beyond this, the increased systemic inflammation and altered respiratory mechanics due to obesity could aggravate symptoms. The significance of immunonutrition also merits attention [29]. Dietary elements can modulate immune reactions, potentially influencing asthma’s severity and control. Some nutrients might either suppress or enhance inflammation, underscoring the value of considering dietary strategies in tandem with conventional asthma treatments. Delving deeper into the interplay between obesity, immunonutrition, and asthma phenotypes could pave the way for more personalized therapeutic approaches.

To actualize this vision, several areas demand deeper exploration. Our grasp on the diet’s effect on the gut-lung axis and systemic inflammation needs enhancement. Furthermore, elucidating specific diet-gene interactions, understanding long-term impacts, and delving into trained immunity’s role in asthma are paramount. A significant challenge is the wide individual variations in dietary habits, gut microbiota composition, genetics, and environmental exposures. Consequently, comprehensive, longitudinal studies integrating genomics, metabolomics, and microbiome analysis across diverse populations are essential.

Looking forward, we anticipate a blend of systems biology and multidisciplinary collaboration to achieve a comprehensive grasp of the diet-immune-asthma interplay. A promising domain is ‘asthma nutrigenomics,’ where genetic data guide dietary recommendations, enhancing personalized prevention of asthma episodes [30]. Moreover, as we delve deeper into trained immunity, certain dietary components could potentially introduce groundbreaking therapeutic strategies.

Recent findings on asthmatic trained immunity, or ‘innate memory,’ are particularly intriguing. Studies in immunometabolism suggest that ‘inflammatory memory’ might explain the recurrent inflammatory patterns observed in certain asthma subtypes. The potential of diet to modulate this memory could pave the way for innovative preventive strategies. Moreover, insights from these studies could illuminate how dietary changes might alter immune cell metabolic shifts, impacting asthma’s pathology.

Existing literature indicates a correlation between diet, microbial shifts, and asthma severity. While the precise cause-and-effect relationship between microbiome alterations and immune responses remains elusive, dietary interventions can certainly enhance gut microbiome health and, by extension, immunity. Strategies such as incorporating probiotics and antioxidant-rich foods underscore this interplay between gut health and immunity. Given recent insights into the role of metabolic pathways in asthma, targeting these pathways presents a promising therapeutic approach, especially within the emerging field of immunometabolism.

1.7. Conclusion

Despite some advancements and discoveries, the relationship between diet, immunity, and asthma remains enigmatic. Current research emphasizes the promise of precision nutrition as a therapeutic strategy for asthma. While challenges persist in treating this prevalent respiratory condition, its connection to diet offers a beacon of hope for future interventions.

Declaration of financial/other relationships

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.