Food intolerances, allergies and the microbiota: what science really tells us

Allergy and intolerance: two biologically different phenomena

Speaking generally about “food intolerance” risks placing very different conditions under the same label. From a medical point of view, however, it is essential to distinguish food allergy, malabsorption or enzyme deficiency, pharmacological or metabolic reactions, and other gastrointestinal disorders.

A particularly clear example is lactose.

So-called “lactose intolerance” is not an allergy. It is generally the result of reduced activity of the lactase enzyme, which is necessary to hydrolyze lactose into glucose and galactose. When lactose is not adequately digested, it reaches the colon, where it is fermented by the microbiota and can cause bloating, abdominal pain, flatulence, and diarrhea in susceptible individuals.

The hydrogen and methane breath test, combined with symptom assessment, is one of the tools used to study carbohydrate malabsorption, including lactose. However, European guidelines emphasize that the mere production of hydrogen is not sufficient: it must be correlated with the onset of symptoms during the test.

Food allergy, on the other hand, follows a different logic.

In IgE-mediated forms, prior immunological sensitization leads to the production of specific IgE antibodies against certain allergens. Subsequent contact with the allergen can activate mast cells and basophils and cause the release of mediators, including histamine. Urticaria, angioedema, vomiting, bronchospasm, and, in the most severe cases, anaphylaxis can occur rapidly.

For this reason, an IgE-mediated food allergy should not be confused with a simple digestive disorder. Current EAACI guidelines recommend a diagnostic pathway based on medical history, specific IgE tests and/or prick tests, and, when necessary, an oral food challenge performed in a controlled medical setting.

And what about so-called “delayed food allergies”?

It is precisely on this point that considerable terminological confusion has arisen in recent decades.

There are indeed forms of non-IgE-mediated food allergy and mixed IgE/non-IgE forms. Some of these can manifest with a delay after food intake and involve cellular mechanisms different from those of IgE-mediated anaphylaxis.

However, it is not scientifically correct to turn this concept into the theory that a generic “delayed allergy” could be diagnosed through food IgG panels.

The major scientific societies in allergology do not consider food-specific IgG or IgG4 a valid diagnostic test for identifying allergies or intolerances. The EAACI has emphasized that the presence of IgG4 to a food generally reflects the body's exposure to that food and can be associated with phenomena of immunological tolerance, not a disease.

Even the most recent EAACI guidelines on the diagnosis of IgE-mediated allergy explicitly recommend not using IgG and IgG subclasses alone for diagnosis.

This is an important point because a positive result obtained through a panel of hundreds of foods can lead a person to eliminate numerous foods from their diet without evidence of a causal relationship between those foods and the symptoms.

The same applies to cytotoxic tests, applied kinesiology, electrodermal tests, and other unvalidated methods. Literature reviews and scientific societies have highlighted their poor or absent diagnostic utility.

However, evidence-based medicine does not mean ignoring the patient's symptoms. It means looking for the cause using appropriate tools.

Food tolerance is a dynamic immunological process

The intestinal immune system is in daily contact with a huge amount of antigens from food and microorganisms.

Most of these contacts do not produce a pathological response. On the contrary, the intestine must continuously develop tolerance to harmless substances.

Regulatory T cells, the epithelial barrier, dendritic cells, and metabolites produced by the microbiota play an important role.

It is therefore more correct to think of food tolerance as a dynamic balance between the intestinal barrier, microbiota, and immune system, rather than as a static mechanism.

When this balance is altered, very different conditions can appear: from simple intestinal fermentation to true immunological diseases.

However, this does not mean that every instance of bloating, reflux, headache, or skin disorder is necessarily caused by “food inflammation.”

Differential diagnosis remains essential.

The microbiota as an interface between diet and the immune system

The intestinal microbiota represents a fundamental component of the gastrointestinal ecosystem. It is not simply a collection of bacteria present in the colon: it is a metabolic community capable of transforming dietary components into biologically active molecules.

Among these, short-chain fatty acids, especially acetate, propionate, and butyrate, are particularly important.

These molecules derive largely from the microbial fermentation of fiber and can interact with intestinal and immune cells through specific receptors and epigenetic mechanisms. They are involved in maintaining the intestinal barrier and regulating the immune response.

This is one of the reasons why the quantity and quality of fiber introduced through the diet can influence not only intestinal regularity, but also the microbial ecosystem and its metabolic functions.

A systematic review of studies conducted in humans has shown that different types of fiber can alter the production of short-chain fatty acids and the composition or activity of the microbiota, although the response varies considerably from person to person.

This last aspect is particularly important: there is no “ideal” microbiota that is the same for everyone.

Fiber: not just intestinal regularity

Dietary fiber is not completely digested by human enzymes and reaches the colon in varying amounts, where it can become a substrate for numerous microorganisms.

Legumes, vegetables, whole fruit, nuts, seeds, and whole grains represent important sources of different types of fiber.

Inulin and fructooligosaccharides are examples of fermentable substrates that can favor specific microbial groups. Fermentation produces metabolites such as butyrate, which contributes to the physiology of the intestinal epithelium and communication between the microbiota and the immune system.

However, this does not mean that “more fiber” is always synonymous with “better.”

In a person with particular intestinal sensitivity, a sudden increase in fermentable fiber can temporarily cause gas and abdominal distension. The response depends on the type of fiber, the quantity, the speed with which it is introduced, intestinal transit, and the individual composition of the microbiota.

The most rational strategy is therefore to gradually increase plant variety, observing the individual response, rather than demonizing fiber because of the symptoms that may appear during an adaptation phase.

Antibiotics and microbiota: a relationship to be used with caution

Antibiotics have revolutionized medicine and, when indicated, can be life-saving drugs. The problem is not their appropriate use, but unnecessary or repeated exposure.

Antibiotics can profoundly alter the intestinal ecosystem. The consequence is not necessarily a simple “permanent destruction” of the microbiota: the response depends on the drug, the duration of therapy, the dose, age, and individual characteristics.

Numerous observational studies have found associations between early exposure to antibiotics and an increased risk of certain allergic diseases. A meta-analysis published in Chest, for example, found an association between exposure to antibiotics in the first year of life and the subsequent development of asthma, but the same authors highlighted the limitations of observational studies and the need for further prospective studies.

A more recent systematic review analyzed 15 studies involving over 1.5 million children and confirmed an association between early exposure to antibiotics, microbiota alterations, and a higher frequency of certain allergic conditions; however, in this case too, association does not automatically mean causality.

The clinically correct conclusion is simple: antibiotics should be used when there is a clear medical indication, not as a general preventive treatment.

The role of proton pump inhibitors

A similar reasoning applies to proton pump inhibitors, such as omeprazole, pantoprazole, lansoprazole, and esomeprazole.

These drugs are not simply “gastroprotectors”: they reduce gastric acid secretion by inhibiting the H+/K+-ATPase of gastric parietal cells.

They are very useful drugs in numerous clinical conditions and should not be demonized. However, prolonged use must be periodically re-evaluated when there is no clear indication to continue it.

The reduction of gastric acidity indeed alters the environment in which ingested microorganisms pass through the stomach and can change the composition of the microbiota. A systematic review of sequencing studies found, in PPI users, changes in the microbial composition of the gastrointestinal tract, including variations in certain bacterial groups.

The association between prolonged PPI therapy and vitamin B12 status has also been studied. The evidence is not completely uniform, but a recent systematic review found changes in certain biomarkers of vitamin B12 status in subjects undergoing chronic treatment.

Therefore, in this case too, the principle is not “never PPI,” but PPI when indicated, at the appropriate dose and for the necessary duration.

Elimination diet or dietary retraining?

When a food is responsible for a true food allergy, its management must be entrusted to a doctor expert in allergology and, when necessary, to a dietitian.

In confirmed IgE-mediated allergies, avoiding the allergen remains a fundamental element of management, along with an individual treatment plan and the management of any risk of anaphylaxis. The most recent EAACI guidelines also include, in selected patients, specific immunotherapy strategies and biologic drugs.

The case of an unexplained gastrointestinal disorder is different.

An extremely restrictive diet based solely on a panel of presumed “intolerances” can unnecessarily eliminate cereals, dairy, legumes, fruit, and other important foods, increasing the risk of nutritional imbalances and making eating progressively more difficult.

Food rotation can be used in some individualized dietary contexts, but it cannot be presented as a universally proven therapy for a presumed “delayed food allergy.” The available scientific evidence does not justify this generalization.

Eating slowly: a simple behavior with physiological bases

The way we eat also influences digestive physiology.

Digestion begins in the mouth: chewing, salivation, and bolus formation represent the first stages of the digestive process.

Eating slowly also promotes greater sensory exposure to food and can facilitate the recognition of satiety.

However, the idea that chewing alone “activates a slimming signal” through a single brain receptor should be considered with caution. Appetite regulation is a much more complex system, in which signals from the stomach, intestine, adipose tissue, and central nervous system interact, including ghrelin, leptin, GLP-1, PYY, cholecystokinin, and insulin.

There is therefore no single molecule capable of explaining hunger, satiety, and body weight on its own.

A practical habit can still be useful: put down the cutlery while chewing, avoiding immediately preparing the next bite. It is a small adjustment that can reduce the speed of the meal and increase food awareness.

Stress, sleep, and the gut: an integrated system

The gastrointestinal system does not work separately from the brain.

The gut-brain axis includes nervous, endocrine, immune, and metabolic pathways. Stress can alter motility, gastrointestinal secretions, pain perception, and interactions with the microbiota.

Insufficient sleep can also alter the regulation of appetite and metabolism.

This does not mean that anxiety and stress are the cause of every intestinal disorder. Rather, it means that gastrointestinal symptoms are the result of the interaction of numerous systems and that a complete assessment should consider them all.

Eating in a calm environment, taking time for the meal, and reducing digital distractions are therefore reasonable behavioral strategies, even independently of any theory about “toxins.”

The immune system should not be “turned off”

Another important concept concerns inflammation.

Acute inflammation is a fundamental physiological response. When tissue is damaged or infected, the body activates a coordinated series of mechanisms designed to eliminate the cause of the damage and promote repair.

Chronic inflammation, on the other hand, can become pathological when persistent stimuli maintain immune activation over time.

However, it is not correct to state that every inflammatory manifestation should be left untreated or that anti-inflammatory drugs and corticosteroids “block healing” in general.

Corticosteroids, for example, are highly effective drugs precisely because they modulate the immune response and are used in numerous inflammatory and allergic conditions. Their prolonged use can cause significant adverse effects, but this is different from stating that they are inherently harmful or that they simply shift “toxins” from one organ to another.

Modern medicine therefore seeks to modulate a pathological immune response, not to indiscriminately shut down the immune system.

Diet, microbiota, and metabolism

The relationship between microbiota and metabolism is today one of the most interesting fields in biomedical research.

Diet rapidly changes the availability of substrates for intestinal microorganisms; these, in turn, produce metabolites capable of interacting with the host's metabolism.

Short-chain fatty acids represent one of the most studied examples. They can influence intestinal barrier function, energy metabolism, and immune response.

However, it is necessary to abandon one of the most widespread simplifications of recent years: the Firmicutes/Bacteroidetes ratio cannot be used as a simple individual “obesity index”.

Current knowledge shows, in fact, a much more complex relationship, depending on bacterial species and strains, diet, medications, age, physical activity, environment, and the host's genetic characteristics.

The microbiota is not a switch that determines “thin” or “fat”.

It is a dynamic ecosystem that participates in the regulation of metabolism together with many other systems.

Movement and metabolic health

Diet is not the only determinant of metabolism.

Physical activity modifies insulin sensitivity, muscle function, oxidative capacity, and energy expenditure. Regular exercise also contributes to the preservation of muscle mass, a particularly important element with advancing age.

In recent years, irisin has also been studied, a myokine associated with muscle activity and communication between muscle and adipose tissue. Some experimental studies have hypothesized a role in the modulation of energy metabolism and adipose tissue, but the physiology of irisin in humans is much more complex than early publications suggest.

The idea that exercise would necessarily produce a generalized transformation of white fat into brown fat through a single mechanism is also no longer considered a sufficient explanation.

The most solid evidence remains much simpler: regular physical activity improves metabolic and cardiovascular health and contributes to the maintenance of muscle mass and functional capacity.

A new food literacy

The real challenge, therefore, is not to divide foods into “good” and “bad”, nor to identify dozens of foods to eliminate through a test.

It is to learn to correctly read the relationship between food, the organism, and the biological context.

A health-oriented diet should favor variety, an adequate presence of plant-based foods and fiber, legumes, whole grains when tolerated, whole fruit, nuts and seeds, appropriate protein sources, and a limitation of ultra-processed foods rich in added sugars, salt, and low-quality fats.

Fiber, in particular, is not simply a substance that “fills the intestine”: it is one of the main substrates through which diet interacts with the microbiota.

Contemporary literature shows, in fact, that fiber can act both directly on the epithelium and immune cells, and indirectly through the microbial production of metabolites such as short-chain fatty acids.

The concept of “food intolerance”, therefore, deserves to be used with precision. A lactase deficiency is not an allergy; an IgE-mediated allergy is not a simple digestive disorder; a positive food IgG test does not prove an allergy; bloating after a food does not automatically identify an immunological reaction.

And above all, a real symptom does not necessarily imply that the test attributing a cause to it is scientifically valid.

The most useful medicine is that which manages to hold these two principles together: listening carefully to what the patient reports and, at the same time, subjecting every biological explanation to the quality of the available evidence.

Essential bibliographic references

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