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.

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References: 

Clancy A, Borody T. (2021). Improvement in Food Intolerance Symptoms after Pretreatment with Antibiotics Followed by Faecal Microbiota Transplantation: A Case Report, Case Rep Clin Nutr, 4:7–13 

Nance CL, Deniskin R, Diaz VC, Paul M, Anvari S, Anagnostou A. (2020). The Role of the Microbiome in Food Allergy: A Review. Children (Basel), 7(6):50

Oak SJ, Jha R. (2019). The effects of probiotics in lactose intolerance: A systematic review. Crit Rev Food Sci Nutr, 59(11):1675-1683

Rinninella E, Raoul P, Cintoni M, Franceschi F, Miggiano GAD, Gasbarrini A, Mele MC. (2019). What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases. Microorganisms, 7(1):14

Valdes AM, Walter J, Segal E, Spector TD. (2018). Role of the gut microbiota in nutrition and health. BMJ, 361:k2179

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