📘 Gut microbiome and the risk of type 1 diabetes

The gut microbiome represents 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, very resistant organisms). The greatest density of the microbiome is found in the large intestine. In the colon you have approximately tens of trillions of bacteria, belonging to hundreds of different species. Your microbiota is unique, like a fingerprint, and is formed from birth, under the influence of mode of birth, breastfeeding, diet, environment and exposure to medications [1].

These microorganisms are not just simple stowaways. They help you digest dietary fibers, produce vitamins (vitamin K and some from the B complex), train the immune system and maintain the integrity of the intestinal barrier. When the composition of the microbiota is balanced, we speak of eubiosis, a state associated with metabolic and immune health. When this balance is broken, either through loss of diversity or through growth of pro-inflammatory bacteria, dysbiosis appears. This is involved in many chronic diseases, including autoimmune diseases, among which T1D [1].

Yes, people with T1D tend to have a microbiome with reduced microbial diversity and a modified ratio between the main bacterial groups, especially 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 some Bacteroides species. These changes reduce the production of protective metabolites and can favor low-grade chronic inflammation [2].

An important aspect is that these changes do not appear only after the clinical onset of T1D. In children with 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 just a consequence of the disease, but could contribute to the autoimmune process that destroys pancreatic beta cells. The cause-effect direction remains under study, but the microbial profile of a child at risk could possibly offer useful clues about the future trajectory of the disease [2].

The way you were born influences the first microbial colonization of your intestine. In vaginal birth, the baby comes into contact with the mother's vaginal and intestinal microbiota and is colonized mainly with species such as Lactobacillus and Bifidobacterium. These bacteria help with the maturation of the immune system and with the development of a healthy intestinal barrier. In cesarean birth, the first microorganisms colonizing the newborn come more from the skin, from the hospital environment and from the skin flora of the medical personnel, which significantly changes the initial composition of the microbiota [3].

This different colonization 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 prevention but only a small delay. To correct this difference, an intervention called "vaginal seeding" was 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 due to infectious risk and lack of solid evidence regarding the benefit. Exclusive breastfeeding remains the most effective method of supporting the development of a healthy microbiota, regardless of the mode of birth [3].

Probiotics are live microorganisms that, when administered in adequate amounts, can provide a benefit for the host. The proposed mechanisms by which probiotics could protect against T1D involve modulation of the immune response, strengthening of the intestinal barrier, competition with pathogenic bacteria and increased production of short-chain fatty acids. Early administration of probiotics, in the first months of life, could be associated with a lower risk of islet autoimmunity in children with genetic predisposition. The effect could depend on the timing of administration and on the bacterial strains used [4].

Currently there is no firm clinical recommendation for the use of probiotics as a strategy to prevent T1D. Differences between strains are large, and one commercial product is not equivalent to another, even if the labels seem similar. Probiotics may be useful for certain digestive situations, but should not be considered a preventive treatment for diabetes. If you are thinking of using them for yourself or for your child, discuss with your doctor about strain, dose and duration of administration, but do not think of the goal of T1D prevention [4].

The intestinal wall functions as a selective filter. The cells of the epithelium are tightly joined together, allow the absorption of nutrients and block the passage into the circulation of large molecules, bacterial fragments and food antigens (which would cause allergies). When these junctions relax, we speak of increased intestinal permeability or "leaky gut". Patients with T1D have somewhat looser connections between intestinal cells [5].

If the intestinal barrier becomes a little more permeable, some bacterial and food antigens manage to reach the immune system in the intestinal wall, where a large part of the body's immune cells are located. In a person with genetic predisposition, this repeated exposure can contribute to the loss of immune tolerance and could under certain conditions contribute to the appearance of beta cell autoimmunity. Increased intestinal permeability is not sufficient to trigger autoimmunity and T1D, but could be an important piece in a puzzle that includes genetics, microbiota and environmental factors. Maintaining a healthy intestinal mucosa through balanced nutrition, fiber and avoiding the unnecessary use of antibiotics is a conduct with multiple benefits [5].

Antibiotics save lives, but do not act selectively. When you treat an infection, the antibiotic also destroys beneficial bacteria from the intestine. 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 antibiotic course can reduce diversity, can temporarily eliminate entire species and can favor the growth of inappropriate bacteria. The microbiota partially recovers after the end of antibiotic treatment, but complete recovery is not guaranteed, especially when repeated courses or broad-spectrum antibiotics are administered [6].

Epidemiological studies have observed an association between frequent use of antibiotics in early childhood and a higher risk of immune-mediated diseases, including T1D. Association does not necessarily mean causality, 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 necessary, but to use them judiciously, only on the doctor's indication, for confirmed or highly probable bacterial infections, and not for trivial respiratory viral infections [6].

Short-chain fatty acids, abbreviated SCFA, are produced when bacteria in the colon ferment dietary fibers 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 intestinal 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 the regulation of appetite and energy metabolism [7].

In the context of T1D, SCFA 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 one's own tissues. At the same time, SCFA strengthen the intestinal barrier and reduce local inflammation, which limits the body's exposure to irritating fragments coming from the intestine that have escaped into the blood. People with T1D tend to have fewer butyrate-producing bacteria and lower SCFA levels. There is not yet a validated therapeutic intervention based on SCFA, but it seems intuitive 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 fibers are divided into fermentable and non-fermentable. Fermentable fibers, such as those from oats, legumes, fruits, 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 fibers, such as those from wheat bran, contribute mainly to stool volume and to intestinal transit. A varied diet, rich in diverse plants, supports a microbiota with many species, and this diversity is a recognized marker of intestinal health [8].

The modern diet, dominated by processed products, refined sugars and poor-quality fats, is generally low in fiber. This deficit is called "fiber gap" and is associated with a reduction of beneficial bacteria, with low-grade inflammation and with a higher risk of metabolic and autoimmune diseases. There is no miracle regimen for the prevention of T1D, but the general principles of a diet with great vegetable variety, whole grains, legumes, fruits, vegetables, nuts and seeds are supported by international guidelines, including those for diabetes. What you could do is increase fiber intake gradually, to allow your microbiota to adapt and to avoid digestive discomfort [8].

Fecal microbiota transplantation, abbreviated FMT, means the transfer of processed feces from a healthy, rigorously selected donor, to the intestine of a patient. The procedure is performed by colonoscopy, nasoduodenal tube or oral capsules. Currently, FMT has only one clearly validated indication, namely recurrent or severe Clostridioides difficile infection, where the results are very good. In other diseases, including T1D, FMT is considered strictly experimental, without clear evidence regarding the benefit [9].

A few preliminary studies in people recently diagnosed with T1D 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 are related to the variability of the donor source, the risk of transmitting infectious agents, the lack of standardization and long-term effects still unknown. FMT is not recommended for the prevention or treatment of T1D [9].