Although every part of our body is inhabited by microorganisms, sight is by far the largest concentration in our intestines. The primary function is to process food into absorbable components. It should therefore come as no surprise that in diseases that are primarily related to a dysregulation of the metabolism, a relationship with (disturbances of) the microbiome is found. However, this relationship is not unambiguous.

Diet is known to strongly influence the composition of the microbiome (1,2). The influence is not a one-way street, for example between the intestinal wall cells, cells of the immune system, and the microbiome (3). Diseases that have a strong relationship with a disturbed metabolism are:

Obesity is a risk factor for a wide range of diseases, such as type 2 diabetes, cardiovascular disease, and various types of cancer (4). Building body weight requires nutrients that are absorbed through the gut and it is therefore obvious to investigate a possible influence of the gut microbiome. The first studies that showed a convincing link between body weight and microbiome were conducted with sterile mice (without a gut microbiome), which remained much leaner than normal mice despite eating more. Transplantation of the microbiome from normal mice to these sterile mice leads to a significant increase in body weight and transplantation of the microbiome from obese mice leads to an even greater increase in body weight (1,4,5). This is a strong indication of a causal link between the microbiome and obesity (5). In people with obesity, differences in microbiome composition compared to lean people are found (5). These microbiome abnormalities are reduced when patients lose weight (regardless of the type of diet) and the normalization of the microbiome is also correlated with the decrease in body weight and not with the amount of calories they consume (4). In a study in which obese people received a "poo transplant," the result was reduced insulin resistance, but no measurable reduction in body weight after six weeks (5-7). Nevertheless, this shows the potential of interventions that directly affect the microbiome, as insulin resistance plays an important role in obesity and related diseases and normalization of insulin sensitivity is an important first step towards improved metabolic health.

This condition can be seen as the connecting element between all the metabolic diseases discussed here. Metabolic syndrome is characterized by obesity, a disturbed lipid profile, glucose intolerance, high blood pressure, and an increased risk of cardiovascular disease and type 2 diabetes (8,9). This means that the indications for a role of the microbiome in, for example, obesity, impaired glucose metabolism and diabetes also apply to metabolic syndrome (1,4,5,8). These indications include the causal relationship between microbiome transplantation and weight gain in laboratory animals, that differences are found in the composition and diversity of the microbiome between lean and obese individuals and between people with and without diabetes, and the fact that the microbiome influences systemic low-grade inflammation. The study on 'faecal transplantation' in obese subjects mentioned under the topic of obesity involved people with an established metabolic syndrome and the fact that systemic insulin resistance improved significantly is a strong indication that microbiome adaptation may have a beneficial effect on the characteristics of metabolic syndrome (6,7).

In this process, the insulin-producing beta cells in the pancreas are destroyed by an autoimmune reaction (10). There is a large increase in type 1 diabetes worldwide that cannot be explained by genetic factors (11). In animal research, modification of the microbiome via antibiotics, probiotics, or faecal transplantation appears to influence the course of type 1 diabetes. There also appears to be a correlation between antibiotic use and type 1 diabetes in humans. Several indications have been found for the presence and role of a so-called 'leaky gut' in type 1 diabetes patients, which can result in immune responses that can lead to the destruction of beta cells (10). As with many other diseases, type 1 diabetes also has abnormalities in the composition and diversity of the microbiome (10, 12). Of particular importance in type 1 diabetes is that it often develops at an early age and that the microbiome of children undergoes significant changes. In children with genetic predispositions, there appears to be a difference between the microbiome of those who later develop type 1 diabetes and those who do not, even before autoimmune reactions against beta cells are observed, with the differences appearing to increase around the time the children start solid food (13). Finally, there is initial evidence that very early application of probiotics (in the first four weeks after birth) in children with a genetic predisposition to type 1 diabetes leads to a lower risk of autoimmune activity against beta cells, which may help to delay or prevent the onset of type 1 diabetes (13).

The exact way in which type 2 diabetes develops is not yet fully known (11). What is certain is that the regulation of blood sugar (glucose regulation) is disrupted by declining insulin production in the context of insulin resistance. Interestingly, as is only recently becoming apparent, the gut can influence glucose homeostasis (14). An important point in the light of impaired glucose regulation as a central characteristic of type 2 diabetes is that the intestines detect and communicate information about the properties of the food consumed to other organs and that this has a measurable effect on the various forms of regulation, including glucose regulation. The microbiome plays a role in this detection and communication of food information (14). In type 2 diabetes, an increased level of inflammation also plays a role and, as noted in the introduction, the microbiome influences this (4,15). In addition, it has been found that low diversity of the microbiome is correlated with, among other things, low-grade inflammation and insulin resistance and, conversely, that the composition of the microbiome in diabetics differs from healthy individuals (4,15). In addition, the first clinical studies with probiotics show cautious positive effects on certain parameters such as insulin resistance and HbA1c in the short term (16).