Obesity, Diabetes, Metabolic syndrome

Impression of the publications on the relevance of the microbiome

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 many diseases, such as type 2 diabetes, cardiovascular disease, and various cancers (4). The build-up of body weight requires nutrients to be absorbed through the gut and it is therefore obvious to investigate a possible influence of the gut microbiome. The first studies to show a convincing link between body weight and microbiome were performed with sterile mice (without gut microbiome), which remained much leaner than normal mice despite eating more. Transplantation of the microbiome from normal mice to these sterile congeners 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 relationship between the microbiome and obesity (5). Differences in microbiome composition compared to lean people are found in obese people (5). These microbiome abnormalities diminish as patients lose weight (regardless of diet type) and where the normalization of the microbiome also correlates 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 “poop transplant,” the result was reduced insulin resistance, but no measurable lower body weight after six weeks (5-7). Nevertheless, it 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.

The metabolic syndrome
This condition can be seen as the connecting element between all the metabolic diseases discussed here. The 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). The indications for a role of the microbiome in, for example, obesity, disturbed glucose metabolism and diabetes also apply to the metabolic syndrome (1,4,5,8). These indications concern, among other things, 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 people and between people with and without diabetes, and the fact that the microbiome has has systemic low-grade inflammation. The ‘faecal transplantation’ study in obese subjects referred to under the subject of obesity involved people with an established metabolic syndrome and the fact that systemic insulin resistance improved significantly is a strong indication that adaptation of the microbiome may have a beneficial effect on the characteristics of metabolic syndrome (6,7).

Diabetes mellitus type 1
In this case, 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, adaptation of the microbiome via antibiotics, probiotics or poo transplantation has been found to influence the course of type 1 diabetes. In humans, too, there appears to be a correlation between antibiotic use and type 1 diabetes. Various indications have been found for the presence and role of a so-called ‘leaky gut’ in type 1 diabetes patients, which may result in immune reactions 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 a young age and that the microbiome of children undergoes profound changes. In children with a genetic predisposition, even before autoimmune reactions against beta-cells are observed, there appears to be a difference between the microbiome of those who later develop type 1 diabetes and those who do not, with the differences appearing to increase around the time the start children on solid foods (13). Finally, there are first indications that very early use 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 delay or prevent the onset of type 1 diabetes (13).

Diabetes mellitus type 2
The exact way in which type 2 diabetes develops is not yet fully known (11). It is certain that the regulation of blood sugar (glucose regulation) is disrupted by decreasing insulin production in the context of insulin resistance. Interestingly, as is only recently becoming apparent, the gut can affect glucose homeostasis (14). An important point in the light of impaired glucose regulation as a central feature 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 nutritional information (14). In addition, an increased degree of inflammation also plays a role in type 2 diabetes and, as noted in the introduction, the microbiome influences this (4,15). In addition, it has been found that a low diversity of the microbiome is correlated to, among other things, low-grade inflammation and insulin resistance and, conversely, that in diabetics the composition of the microbiome differs from healthy persons (4,15). The first clinical studies with probiotics also show cautious positive effects on certain parameters such as insulin resistance and HbA1c in the short term (16).

1. Janssen AWF, Kersten S. The role of the gut microbiota in metabolic health. FASEB J Off Publ Fed Am Soc Exp Biol. 2015; 29: 3111-23.
2. David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2013; 559-63.
3. Shulzhenko N, Morgun A, Hsiao W, Battle M, Yao M, Gavrilova O, Orandle M, Mayer L, Macpherson AJ, McCoy KD, et al. Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut . Nat Med. 2011; 17: 1585-93.
4. Barlow GM, Yu A, Mathur R. Role of the Gut Microbiome in Obesity and Diabetes Mellitus. Nutr Clin Pract Off Publ Am Soc Parenter Enter Nutr. 2015; 30: 787-97.
5. Meijnikman AS, Gerdes VE, Nieuwdorp M, Herrema H. Evaluating Causality of Gut Microbiota in Obesity and Diabetes in Humans. Endocr Rev. 2017;
6. Marotz CA, Zarrinpar A. Treating Obesity and Metabolic Syndrome with Fecal Microbiota Transplantation. Yale J Biol Med. 2016; 89: 383-8.
7. Vrieze A, Nood EV, Holleman F, Salojarvi J, Kootte RS, Bartelsman JFWM, Dallinga-Thie GM, Ackermans MT, Serlie MJ, Oozeer R, et al. Transfer of Intestinal Microbiota From Lean Donors Increases Insulin Sensitivity in Individuals With Metabolic Syndrome . Gastroenterology. 2012; 143: 913-916.e7.
8. Mazidi M, Rezaie P, Kengne AP, Mobarhan MG, Ferns GA. Gut microbiome and metabolic syndrome. Diabetes Metab Syndr. 2016; 10: S150-157.
9. Festi D, Schiumerini R, Eusebi LH, Marasco G, Taddia M, Colecchia A. Gut microbiota and metabolic syndrome. World J Gastroenterol WJG. 2014; 20: 16079-94.
10. Gomes AC, Bueno AA, de Souza RGM, Mota JF. Gut microbiota, probiotics and diabetes. Nutr J. 2014; 13:60.
11. Semenkovich CF, Danska J, Darsow T, Dunne JL, Huttenhower C, Insel RA, McElvaine AT, Ratner RE, Shuldiner AR, Blaser MJ. American Diabetes Association and JDRF Research Symposium: Diabetes and the Microbiome. Diabetes. 2015; 64: 3967-77.
12. Dunne JL, Triplett EW, Gevers D, Xavier R, Insel R, Danska J, Atkinson MA. The intestinal microbiome in type 1 diabetes. Clin Exp Immunol. 2014; 177: 30-7.
13. Knip M, Honkanen J. Modulation of Type 1 Diabetes Risk by the Intestinal Microbiome. Curr Diab Rep. 2017; 17: 105.
14. Haluzik M, Kratochvilova H, Haluzikova D, Mraz M. Gut as an emerging organ for the treatment of diabetes: focus on mechanism of action of bariatric and endoscopic interventions. J Endocrinol. 2018; 237: R1-17.
15. Tilg H, Moschen AR. Microbiota and diabetes: an evolving relationship. Gut. 2014; 63: 1513-21.
16. Kasinska MA, Drzewoski J. Effectiveness of probiotics in type 2 diabetes: a meta-analysis. Pol Arch Intern Med. 2015; 125: 803-13.


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