How intolerances affect the Microbiome

Microbes, especially bacteria, have coevolved with humans over millennia and we both have a symbiotic relationship. A highly diverse population of microorganisms living in our body plays important roles in our health. Gut microbes are key regulators of digestion and are involved in human nutrition, metabolism and immune functions. An imbalance of this microbial community has been related to disease, including food allergies and intolerances. Restoring the microbial balance through diet and other means is now being investigated to treat food allergies and alleviate food intolerance symptoms.

Microbes, microbiota and microbiome

Microbes –these microscopic organisms too small to be seen with the naked eye–  are everywhere and this includes also our body. Some microbes, such as the opportunistic microbes or the pathogens, can make us sick, but some others, the beneficial microbes, are important for our nutrition and heath. 

The community of microbes found in a particular part of the body is known as microbiota. This includes mainly bacteria, but also other microorganisms such as fungi, protozoa and viruses. Skin, vagina, and respiratory and gastrointestinal tracts are the main body parts where microbes reside, so there is a skin microbiota, an oral microbiota and a gut microbiota, among other microbiota types. The microbiome is the sum of microbes and their genome in a particular location. So there is also a gut microbiome for example, i.e. the gut microbiota plus their genes. 

Hence more than half of human body is not only human but it corresponds to a diverse collection of microbes that play major roles in human health: a sort of a “virtual organ” of the human body. In fact, the human microbiome is thought to be formed of as many microbes as human cells representing around 0.45 lb (0.2 kg) in weight!

What is the gut microbiota composition?

Each of us is provided with an individual gut microbiota profile that plays many specific functions in our body. Gut microbiota is shaped in early life and its composition is influenced by many factors such as infant transitions (type of delivery, methods of milk feeding, weaning period), lifestyle (body mass index level, exercise frequency), antibiotic use or dietary and cultural habits. Although there is not a unique optimal composition since there are some differences among individuals, gut microbiota from a healthy adult is composed of around 1,000 species of bacteria, being around 160 species the most represented. 

Around 90% of gut microbiota is represented by two groups or phyla: Firmicutes (including the genera Clostridium, Lactobacillus, Bacillus, Enterococcus, and Ruminicoccus) and Bacteroidetes (including the genera Bacteroides and Prevotella). Less abundant phyla are Actinobacteria (including Bifidobacterium genus), Proteobacteria, Fusobacteria, and Verrucomicrobia. Given that culturing gut microbiota is difficult, all these intestinal microbes have been identified by sequencing their DNA. In particular, the 16S rRNA gene is the most frequently sequenced gene to characterize the gut microbiome.

How does the gut microbiome affect nutrition and health?

The gut microbiome encodes over 3 million genes: that is around 130 times the human genome, which is composed of around 23 thousand genes. Microbial genes produce thousands of metabolites that at the end of the day replace many of the functions of their hosts, influencing the host health. In fact, different levels of evidence, from animal models to human epidemiologic studies, support a role of the gut microbiome in human health. 

The gut microbiota is a key regulator of digestion along the gastrointestinal tract and it plays an important role in the extraction, synthesis, and absorption of many nutrients and metabolites, including bile acids, lipids, amino acids, vitamins, fiber and short-chain fatty acids (SCFAs). The major SCFAs produced by the gut microbiota are acetate, propionate, and butyrate, all of them playing a role in human metabolism. Acetate, the most abundant, is used in cholesterol metabolism and lipid synthesis. Propionate is transferred to the liver, where it regulates glucose synthesis. Butyrate is the main energy source for gut epithelial cells that consume large amounts of oxygen, maintains the oxygen balance in the gut and prevents an imbalance of the gut microbiota community –what is known as dysbiosis–. 

The gut microbiota has other functions in human health. It is also important in reducing the risk of some infections as it has a crucial immune function against the invasion of pathogenic bacteria by inhibiting their growth, consuming available nutrients and/or producing antimicrobial agents, which leads to the maintenance of the gut epithelium integrity. The gut microbiome also regulates the development, homeostasis, and function of innate and adaptive immune cells. 

In general microbiota diversity (a high number of different microbe species) seems to be a good indicator of a “healthy” gut. A lower diversity is considered a marker of gut dysbiosis and it has been related to some diseases as it has been found in metabolic disorders such as obesity, type 2 diabetes, cardiovascular such as hypertension and allergic such as inflammatory bowel disease, psoriatic arthritis, atopic eczema or asthma. The human gut microbiota has also been related to colorectal cancer.

Is there a role of gut microbiota in food allergy?

Immune tolerance is the state of unresponsiveness of the immune system to substances or tissues that can induce an immune response. Food allergy develops when immune tolerance is lost, which results in allergic sensitization and subsequent disease manifestation and progression. The initial exposure to food allergens occurs predominantly through the gastrointestinal tract or skin. In the gastrointestinal tract, the two main factors influencing an immune reaction to food are dietary factors and microbiota composition. Gut microbiome dysbiosis early in life can lead to food allergy development. Studies evaluating the profile of the gut microbiome have shown unique microbial differences in patients with food allergies compared to healthy patients.

Some authors have described the “nutrition–gut microbiome–physiology axis” as an essential link between diet, gut microbiota and allergic disease. Related to this, SCFAs, the metabolites produced by intestinal bacteria through the fermentation of non-digestible fibers, play an important role. Unlike pro-inflammatory Western diets characterized by their high fat, low fiber and highly processed content that contribute to gut microbiome dysbiosis, SCFAs are key signaling molecules that enable “cross-talk” between the gut microbiome and the human host, linking high-fiber diets to better health outcomes and prompting an increase of SCFAs as an option to prevent allergic diseases. 

Microbiota composition has been evaluated in specific food allergies. For example, children with egg allergy showed an enrichment of the Lachnospiraceae and Streptococcaceae families in their gut microbiota, while healthy (non-food allergic) children displayed and enrichment of Leuconostocaceae. Also an enrichment of Clostridia and Firmicutes was found in gut microbiomes of small children with cow’s milk allergy that resolved it later in childhood.

Can gut microbiota manipulation influence food intolerance?

Diet and medication –especially antibiotics– have a strong influence on gut microbiota composition. Microbiota can then be modified through diet. Two examples are prebiotics and probiotics. Prebiotics are substrates selectively used by gut microbiota, leading to specific changes in its composition and eventually providing a health benefit. Prebiotics pass through the upper gastrointestinal tract undigested and serve to stimulate the activity and/or growth of gut microbes. The most studied prebiotic is fermentable dietary fiber. 

Probiotics are live bacteria (mostly Bifidobacterium and Lactobacillus species) and yeasts that, when administrated in a viable form and in proper amounts, are beneficial to human health. They are usually added to yoghurts or taken as food supplements. It has been found that probiotic bacteria in fermented and unfermented dairy products can modify the metabolic activities of gut microbiota and may alleviate the symptoms of lactose intolerance, showing a positive relationship between probiotics and lactose intolerance.

Did you know that fecal microbiota can be transplanted to improve health? 

Beyond diet through prebiotics and probiotics, microbiota composition can also be manipulated by other means. Fecal microbiota transplantation (FMT) is a type of bacteriotherapy (the use of bacteria or their products to treat illness) where, believe or not, stool –which is composed of diverse microbe populations– from a healthy donor is transferred into the gastrointestinal tract of a diseased individual aiming to treat a particular disease. If a malfunctioning kidney, liver or heart can be transplanted to improve people’s life, why don’t transplanting our “virtual organ” the gut microbiota? 

 In FMT, pathogenic or opportunistic microbes are out-competed by the newly introduced bacteria to reshape the host gut microbiome. Compared to probiotic treatments that contain a few bacterial species, FMT involves thousands of gut bacterial species that increase microbial diversity and restore the gut microbiota community structure and diversity to the level of a healthy person. FMT is a novel approach using the gut microbiome as its target for treatment. It is still under investigation but there are some studies showing a potential benefit to treating food allergies and intolerances with FMT. A case report of a female adult with irritable bowel syndrome showed an improvement of her food intolerance symptoms after treatment with FMT. Also, there is a recently completed phase I clinical trial evaluating the safety and tolerability of oral encapsulated FMT administered in adults with peanut allergy.

Recent Insights into Gut Microbiome and Food Allergies

Recent research has significantly advanced our understanding of the gut microbiome’s critical role in immune system regulation, particularly in food allergies. It is becoming clear that the gut microbiota contributes not just to digestion, but also to the regulation of immune responses, including the development of tolerance to food allergens. An imbalance in the microbiome—also known as dysbiosis—may disrupt immune tolerance and increase susceptibility to allergic reactions. Studies have found that individuals with food allergies often have distinct gut microbiome profiles compared to healthy individuals, pointing to the possibility that microbial imbalance may be a key factor in the development of food allergies.

Interestingly, research suggests that gut microbiome diversity plays a vital role in fostering immune tolerance. A more diverse microbiota appears to help maintain a balanced immune system that is less likely to react excessively to harmless substances like food proteins. This highlights the potential of probiotic and prebiotic interventions to restore a healthy microbiome balance, thus mitigating the risk of food allergies.

Emerging therapies targeting gut microbiome restoration, such as fecal microbiota transplantation (FMT) and microbiome-targeted diet adjustments, are gaining traction as potential treatments for food allergies. Through these interventions, there is the hope that individuals with food allergies could achieve greater tolerance, potentially reducing or even eliminating allergic reactions.

Impact of Pandemic-Related Lifestyle Changes on Gut Microbiota

The COVID-19 pandemic has drastically altered lifestyle factors—such as diet, hygiene practices, and increased antibiotic usage—which may have long-term effects on gut microbiota composition. Research has suggested that infants born during the pandemic, particularly those whose caregivers followed more stringent hygiene and limited exposure to outside environments, might exhibit differences in their gut microbiota compared to children born before the pandemic. This shift in microbial exposure may influence the development of allergies and other immune-related conditions later in life.

For example, a reduction in microbial diversity during early childhood, due to limited interactions with the outside environment, could delay the maturation of immune systems. This lack of microbial exposure might increase the risk of developing food allergies and intolerances. These findings underscore the importance of microbial diversity in early life and its role in shaping long-term health, emphasizing the need for a balanced approach to hygiene and diet during the early years.

Advancements in Gut Microbiome-Based Therapies for Food Allergies

The connection between the gut microbiome and food allergies has spurred a wave of innovative treatments aimed at restoring a healthy gut environment. One of the most promising therapies is Fecal Microbiota Transplantation (FMT), where stool from a healthy donor is transferred to a patient’s gastrointestinal tract. FMT aims to replenish beneficial bacteria, enhancing microbial diversity and potentially improving immune tolerance to allergens. Unlike probiotics, which introduce a small number of bacterial species, FMT provides a broad spectrum of microbial species, making it a more comprehensive approach to gut microbiome restoration.

In addition to FMT, researchers are exploring the use of specific probiotics and prebiotics to enhance gut health and prevent allergic reactions. Studies have shown that certain strains of probiotics can boost the immune system and improve gut barrier function, which could be particularly beneficial for individuals with food allergies. Furthermore, a high-fiber diet rich in prebiotics may support the growth of beneficial bacteria, helping to prevent dysbiosis and promote overall immune balance.

The potential for microbiome-based therapies to treat food allergies is still under investigation, but the early results are promising. If further studies confirm their efficacy, these treatments could offer new hope for individuals suffering from food allergies.

Dietary Factors Influencing Gut Microbiota and Food Intolerances

Diet plays a significant role in shaping the gut microbiota, and recent research highlights the impact of dietary patterns on food intolerances. Diets that are high in fiber, antioxidants, and polyphenols have been shown to promote the growth of beneficial microbes, support a healthy gut barrier, and reduce the risk of developing food intolerances. Conversely, diets rich in ultra-processed foods, high fats, and low fiber can disrupt the gut microbiome and lead to increased intestinal inflammation, which can contribute to food intolerances.

One of the most significant dietary factors is fiber. Foods rich in fiber, such as fruits, vegetables, legumes, and whole grains, promote the growth of beneficial gut bacteria that produce short-chain fatty acids (SCFAs). These SCFAs, particularly butyrate, acetate, and propionate, help maintain a healthy gut lining and regulate immune function. A diet high in fiber may also help reduce symptoms of food intolerances by supporting a more balanced microbiome.

In contrast, the Western diet, characterized by high levels of processed foods and low in fiber, has been linked to a reduction in microbiota diversity. This decrease in diversity has been associated with a higher prevalence of conditions like food intolerances, irritable bowel syndrome (IBS), and other inflammatory gut disorders. As a result, nutritionists recommend an anti-inflammatory diet that emphasizes whole foods, fiber, and minimal processed food intake to support gut health and alleviate food intolerance symptoms.

Emerging Research on Cross-Reactivity of Food Allergens

A new area of research that is gaining attention is cross-reactivity in food allergies, where similar protein structures in different foods can trigger allergic reactions in individuals sensitive to one food allergen. For example, individuals allergic to birch pollen may also experience reactions to certain fruits, such as apples and cherries, due to the similarity in protein structures. Understanding the phenomenon of cross-reactivity is crucial in managing food allergies, as it can help to identify potential triggers beyond the commonly known allergens.

This research is particularly important for individuals who experience multiple food allergies, as it could lead to more targeted dietary recommendations and treatments. By identifying the proteins responsible for cross-reactivity, healthcare providers may be able to develop more precise allergy management strategies, reducing the risk of allergic reactions and improving the quality of life for affected individuals.

Conclusion

The complex interplay between the gut microbiome, food intolerances, and immune responses is becoming clearer through ongoing research. From dietary interventions and probiotics to more advanced therapies like FMT, the potential to manipulate the microbiome and alleviate food allergies and intolerances is an exciting avenue of treatment. 

As we learn more about the factors that shape the gut microbiome, including diet, lifestyle, and even pandemic-related changes, we are moving closer to more effective and personalized approaches to managing food allergies and intolerances. This dynamic area of research promises not only to change the way we think about allergies but also to offer new hope for individuals struggling with food sensitivities.

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