The gut microbiome and the risk of type 1 diabetes

The gut microbiome is the totality of microorganisms that live in your digestive tract, together with their genetic material. This true community includes bacteria, viruses, fungi and archaea (simple, single-celled, highly resilient organisms). The greatest density of the microbiome is found in the large intestine. In the colon you have roughly tens of trillions of bacteria, belonging to hundreds of different species. Your microbiota is unique, like a fingerprint, and is shaped from birth onward, under the influence of the mode of birth, breastfeeding, diet, environment and exposure to medicines [1].

These microorganisms are not just stowaways. They help you digest dietary fibre, produce vitamins (vitamin K and some of the B complex), train the immune system and maintain the integrity of the gut barrier. When the composition of the microbiota is balanced, we speak of eubiosis, a state associated with metabolic and immune health. When this balance breaks down, either through loss of diversity or through an increase in pro-inflammatory bacteria, dysbiosis appears. It is implicated in many chronic diseases, including autoimmune diseases, among them type 1 diabetes [1].

Yes, people with type 1 diabetes tend to have a microbiome with lower microbial diversity and an altered ratio between the main bacterial groups, particularly between Firmicutes and Bacteroidetes. There are fewer butyrate-producing bacteria, such as Faecalibacterium prausnitzii and Roseburia, and more bacteria with a pro-inflammatory profile, such as certain Bacteroides species. These changes reduce the production of protective metabolites and can favour low-grade chronic inflammation [2].

An important point is that these changes do not appear only after the clinical onset of type 1 diabetes. In children at genetic risk, microbiota changes have sometimes been observed even before the appearance of specific autoantibodies, therefore before clinical onset. This suggests that dysbiosis is not merely a consequence of the disease, but may contribute to the autoimmune process that destroys the pancreatic beta cells. The cause-and-effect direction is still under study, but the microbial profile of a child at risk may perhaps offer useful clues about the future course of the disease [2].

The way you were born influences the first microbial colonisation of your gut. In vaginal birth, the baby comes into contact with the mother's vaginal and intestinal microbiota and is colonised mainly with species such as Lactobacillus and Bifidobacterium. These bacteria help the immune system to mature and a healthy gut barrier to develop. In caesarean birth, the first microorganisms that colonise the newborn come more from the skin, from the hospital environment and from the skin flora of the medical staff, which significantly changes the initial composition of the microbiota [3].

This different colonisation usually delays the development of a “mature” microbiota and has been epidemiologically associated with a slightly increased risk of immune-mediated diseases. However, this is not a matter of prevention but only a small delay. To correct this difference, an intervention known as “vaginal seeding” has been considered, that is, the controlled transfer of maternal vaginal microbiota onto the skin and mucous membranes of the newborn. This practice is not currently recommended because of the infectious risk and the lack of solid evidence of benefit. Exclusive breastfeeding remains the most effective way to support the development of a healthy microbiota, regardless of the mode of birth [3].

Probiotics are live microorganisms that, when given in adequate amounts, can confer a benefit on the host. The proposed mechanisms by which probiotics could protect against type 1 diabetes involve modulation of the immune response, strengthening of the gut barrier, competition with pathogenic bacteria and increased production of short-chain fatty acids. Early administration of probiotics, in the first months of life, may be associated with a lower risk of islet autoimmunity in children with a genetic predisposition. The effect may depend on the timing of administration and on the bacterial strains used [4].

At present there is no firm clinical recommendation for using probiotics as a strategy to prevent type 1 diabetes. Differences between strains are large, and one commercial product is not equivalent to another, even if the labels look similar. Probiotics may be useful in certain digestive situations, but they should not be regarded as a preventive treatment for diabetes. If you are thinking of using them for yourself or for your child, discuss the strain, dose and duration with your doctor, but do not think of them as a way to prevent type 1 diabetes [4].

The intestinal wall works as a selective filter. The cells of the epithelium are tightly joined together, allow nutrients to be absorbed and block the passage into the circulation of large molecules, bacterial fragments and food antigens (which would cause allergies). When these junctions loosen, we speak of increased intestinal permeability or “leaky gut”. People with type 1 diabetes have somewhat looser connections between the gut cells [5].

If the gut barrier becomes a little more permeable, some bacterial and food antigens manage to reach the immune system in the gut wall, where a large part of the body's immune cells are located. In a person with a genetic predisposition, this repeated exposure can contribute to the loss of immune tolerance and may, under certain conditions, contribute to the appearance of beta-cell autoimmunity. Increased intestinal permeability is not enough on its own to trigger autoimmunity and type 1 diabetes, but it may be an important piece in a puzzle that includes genetics, the microbiota and environmental factors. Maintaining a healthy gut lining through a balanced diet, fibre and avoiding the unnecessary use of antibiotics is a course of action with multiple benefits [5].

Antibiotics save lives, but they do not act selectively. When you treat an infection, the antibiotic also destroys beneficial bacteria in the gut. In small children, especially in the first 2–3 years of life, a period in which the microbiota matures and trains the immune system, each course of antibiotics can reduce diversity, can temporarily wipe out entire species and can favour the growth of unsuitable bacteria. The microbiota partly recovers after antibiotic treatment ends, but full recovery is not guaranteed, especially when repeated courses or broad-spectrum antibiotics are given [6].

Epidemiological studies have observed an association between frequent antibiotic use in early childhood and a higher risk of immune-mediated diseases, including type 1 diabetes. Association does not necessarily mean causation, but the biological mechanism is plausible. Broad-spectrum antibiotics, such as more advanced-generation cephalosporins, have a greater impact on the microbiota than narrow-spectrum penicillins. The practical message is not to avoid antibiotics when they are needed, but to use them judiciously, only on a doctor's advice, for confirmed or highly probable bacterial infections, and not for ordinary respiratory viral infections [6].

Short-chain fatty acids, abbreviated as SCFAs, are produced when bacteria in the colon ferment the dietary fibre that you cannot digest. The most important are butyrate, propionate and acetate. Butyrate is the main source of energy for the cells lining the colon, helps maintain the tight junctions between gut cells and has anti-inflammatory effects. Propionate reaches the liver and influences glucose and lipid metabolism. Acetate circulates throughout the body and plays a role in regulating appetite and energy metabolism [7].

In the context of type 1 diabetes, SCFAs are of interest because they modulate the immune system. Butyrate stimulates the differentiation of regulatory T cells, which keep autoimmune responses in check and maintain tolerance to the body's own tissues. At the same time, SCFAs strengthen the gut barrier and reduce local inflammation, which limits the body's exposure to irritating fragments that come from the gut and have escaped into the blood. People with type 1 diabetes tend to have fewer butyrate-producing bacteria and lower SCFA levels. There is not yet a validated therapeutic intervention based on SCFAs, but it seems sensible to choose a healthy and varied diet that stimulates their natural production [7].

Yes, diet is one of the factors with the fastest and strongest impact on the microbiota. Dietary fibre is divided into fermentable and non-fermentable. Fermentable fibres, such as those in oats, pulses, fruit, vegetables and some whole grains, are the preferred food of beneficial bacteria and a basic source for the production of short-chain fatty acids. Non-fermentable fibres, such as those in wheat bran, contribute mainly to stool bulk and to intestinal transit. A varied diet, rich in a wide range of plants, supports a microbiota with many species, and this diversity is a recognised marker of gut health [8].

The modern diet, dominated by processed products, refined sugars and poor-quality fats, is generally low in fibre. This shortfall is called the “fibre gap” and is associated with a reduction in beneficial bacteria, with low-grade inflammation and with a higher risk of metabolic and autoimmune diseases. There is no miracle diet for preventing type 1 diabetes, but the general principles of a diet with great plant variety, whole grains, pulses, fruit, vegetables, nuts and seeds are supported by international guidelines, including those for diabetes. What you could do is increase your fibre intake gradually, to let your microbiota adapt and to avoid digestive discomfort [8].

Faecal microbiota transplantation, abbreviated as FMT, means the transfer of processed faeces from a healthy, rigorously selected donor into the gut of a patient. The procedure is performed by colonoscopy, nasoduodenal tube or oral capsules. At present, FMT has only one clearly validated indication, namely recurrent or severe Clostridioides difficile infection, where the results are very good. In other diseases, including type 1 diabetes, FMT is considered strictly experimental, without clear evidence of benefit [9].

A few preliminary studies in people recently diagnosed with type 1 diabetes have explored whether FMT from the same person or from another person could slow the destruction of beta cells and prolong the period of partial remission. The results are mixed and do not allow any clinical recommendation. The limitations relate to the variability of the donor source, the risk of transmitting infectious agents, the lack of standardisation and long-term effects that are still unknown. FMT is not recommended for the prevention or treatment of type 1 diabetes [9].