Do ultra processed foods negatively influence immune health?

Currently, there has been an explosion of interest in trying to understand how and why long-term dietary habits impact chronic immune-mediated disorders and responses to infections.

The prevalence of allergic diseases and other immune-mediated diseases (eg, autoimmune disease and type 2 diabetes) has risen dramatically over the last decades, with many nutritional and environmental factors considered to play a role in disease risk and pathology. Equally important is the immune system’s ability to defend against infection, while avoiding collateral damage to host tissues.

The importance of diet was highlighted by several studies during the Covid-19 pandemic, where adults who consumed plant-based or pescatarian diets more regularly seemed to have lower odds of developing severe Covid-19.

The European Academy of Allergy and Clinical Immunology (EAACI) recently published a systematic review on the effects of ultra-processed foods (UPFs) on allergies in children, and the potential immunological mechanisms impacted by UPFs.¹ The results suggest that consumption of UPFs and common ingredients in UPFs seem to be associated with increased occurrence of allergic diseases such as asthma, wheezing, food allergies, atopic dermatitis, and allergic rhinitis, in many, but not all studies included in the systematic review.

This study is consistent with existing reports linking UPF consumption with negative effects on human health. Three previously published systematic reviews noted associations between high UPF consumption and an increased risk of all-cause mortality, including cardiovascular diseases, cerebrovascular diseases, hypertension, cancer, obesity, depression, asthma, and frailty.

In addition, consuming more than three servings of UPFs a day was associated with measures of premature aging (ie, shortened telomeres that protect the ends of chromosomes from becoming frayed or tangled) while consuming more than five servings of UPFs a day was associated with a higher body mass index (BMI) in older volunteers. Lastly, UPF consumption during pregnancy was associated with higher odds of excessive gestational weight, and with increased low-grade systemic inflammation.

The terminology for classifying foods as UPFs was first introduced by NOVA, and NOVA’s classification represents a system based on the nature, extent, and purpose of industrial food processing. Using this system, foods and beverages can be classified as [1] unprocessed or minimally processed foods; [2] processed culinary ingredients; [3] processed foods; [4] UPFs. UPFs include snacks, drinks, ready-to-eat meals, and many other products created mostly or entirely from substances that contain little, if any, intact food.

Many of the manufacturing techniques, additives, and flavour enhancers used for UPFs are designed to help prolong packaged food shelf life, limit microbial growth and spoilage, prevent depuration of ingredients, and improve the appearance or taste of the food.

UPFs are a significant part of the diet for many families due to their affordability and convenience. Current estimates suggest that UPFs provide more than half of the total dietary energy intake in high-income countries such as the United States, Canada, the United Kingdom, and Northern Ireland.

How might UPFs negatively affect the immune system? Diet diversity, especially relating to a diverse variety of fresh foods including fruit and vegetables, have been associated with beneficial effects on the immune system, such as reduced risk of allergy outcomes. In this context, UPFs could facilitate the risk of allergic diseases as UPFs typically lack fresh ingredients, and their high-heat processing can further degrade essential nutrients. Indeed, while the core nutritional content of UPFs is limited in diversity, these foods are typically characterised by the inclusion of a wide variety of chemical compounds, due to the addition of various chemicals and artificial substances to enhance taste, texture, and preservation. Direct effects on immune cells and the gut epithelial barrier are also increasingly being described.

Advanced glycation end products (AGEs) are one example through which UPFs directly impact the immune system. Most UPFs contain high levels of AGEs due to their high sugar content, use of dehydrated ingredients, very high temperature cooking methods (microwaving or frying), and long storage time. AGEs can directly trigger specific receptors on immune cells that lead to inflammatory responses involving both the innate and adaptive immune system.

In addition to AGEs, emulsifiers commonly found in UPFs (such as polysorbate (P)20, P80, and carboxymethyl cellulose) have been associated with disruption of the gut epithelial barrier, which can interfere with mucosal immune tolerance mechanisms leading to local and systemic inflammatory responses. Certain artificial sweeteners have also been shown to directly modulate T-cell responses.

UPFs may also influence the immune system via indirect mechanisms, potentially mediated by UPF effects on the gut microbiome. Commensal microbes within the gut play essential roles in regulation of host metabolic responses, epithelial barrier function, immune education, and immune regulation. Microbial-derived factors – such as short-chain fatty acids, indoles, and polyamines – protect against aberrant inflammatory processes or hypersensitive responses, but also promote effector immune responses that efficiently eliminate pathogens, such as SARS-CoV-2.

While individual microbes, microbial components, and individual metabolites are certainly important, the overall community functional capacity and community metabolic outputs that underpin interactions with the host immune system are perhaps more relevant regarding understanding disease risk. A low-risk microbiome configuration may generate sufficient levels of several regulatory metabolites that are associated with protection from aberrant inflammatory responses.

In contrast, a high-risk microbiome configuration may consistently generate multiple pro-inflammatory metabolites that may contribute to a higher risk of inappropriate immune reactivity.

The EAACI systematic review shows that microbiome composition and metabolism seem to be different in people consuming high levels of UPFs compared to people consuming low levels of UPFs. Specific UPFs linked with microbiome changes include sugar-sweetened beverages, artificially sweetened beverages, and processed meats, while specific UPF components linked with microbiome changes include non-caloric artificial sweeteners and emulsifiers.

Alterations in gut microbiome structure and function in those consuming high levels of UPFs might be due to direct effects of UPF components (eg, emulsifiers) on specific microbes and their production of metabolites, but also might reflect lower dietary intake of microbe-supporting dietary components such as fiber, which is essential for the maintenance of a balanced microbiome.

In conclusion, diet has consistently been linked with diseases that involve some level of immunological dysfunction. The progressive transition in society toward dietary habits characterised by low diversity, and higher consumption of UPFs, could be a driver for the increased prevalence of immune-mediated disorders such as allergic diseases. There is a clear need to better understand the mechanisms of action elicited by UPFs in facilitating the occurrence of allergic diseases, the effects of different compounds, and the eliciting doses.

The existing evidence underscores the importance of dietary choices, perhaps especially during pregnancy and early childhood, highlighting the importance of intervention in early life. The complicated tango between diet, microbiome, epithelial barriers, metabolism, and the immune system may not only be important for disease prevention but may also impact disease management. The coordinated development of scientific validated clinical guidelines and recommendations, public education campaigns, and government policy actions on healthy eating for a healthy immune system are urgently required.

References: