Role of gut microbiota in diabetes

Microbiome refers to all microorganisms and their genetic material living in the body, while microbiota refers to the communities of microorganisms found in different parts of the body (1). The intestinal microbiota is a complex structure that functions like an organ system with the presence of trillions of microorganisms. In individuals, the intestinal microbiota is formed by bacteria from the mother and the environment during birth. The newborn has a sterile folate. After one year of age, the gut microbiota becomes similar to the digestive tract microbiota of a young person. It continues to differentiate and form until the age of three (2).

During birth, the newborn encounters many microorganisms in the vaginal canal, forming the digestive system microbiota. The resulting microbiota is individual-specific and is affected by many internal and external factors during birth. In newborns born by normal delivery, the intestinal microbiota of the newborn is formed by the microorganisms of the genitourinary system of the mother, while it has been observed that the intestinal system is formed similarly to the skin microorganisms in the cesarean section. It affects the gut microbiota in feeding in newborns. Recent studies report that the intestinal microbiota is different in breastfed and formula-fed newborns. breast milk antibodies bifidobacteriaand lactobacillusthey contain commensal bacteria (3, 4).

The digestive system microbiota is in balance under normal conditions. Short-term changes in the microbiota may occur with nutrition and environmental factors, and long-term and permanent changes may occur with aging. Nutritional habits are one of the most important factors affecting the digestive system microbiota. In individuals with a diet rich in carbohydrates, noticeable changes occur in the microbiota. One of the important factors that change the content of the microbiota is the unconscious use of antibiotics. Excessive use of antibiotics has negative effects by increasing antibiotic-resistant pathogens. Species affected in the microbiota as a result of antibiotic treatment may vary between individuals. Also, while some species may take months to recover after antibiotic treatment, it often takes a very long time for bacterial diversity to decline. As the gut microbiota remodels after antibiotic treatment, commensal may allow for the colonization of foreign bacteria or resistant strains. All these are conditions that can cause permanent changes in the microbiota and diseases. In addition, the repeated use of antibiotics makes the microbiota a reservoir with antibiotic resistance genes (5, 6).

The composition of the gut microbiota differs with age. Recent studies with elderly individuals report that they have different gut microbiota composition than younger individuals, and microbiota composition in elderly individuals has been found to be significantly related to nutrition (7, 8).

In recent years, intestinal microbiota has been used in treatment with products such as probiotics and prebiotics. Probiotics are live microorganisms beneficial for the host, while Prebiotics are Bifidobacterium are carbohydrate molecules that stimulate the development of beneficial flora elements such as Symbiotics is the name given to the combination of probiotics and prebiotics (9).

Intestinal microbiota in healthy individuals Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, fusobacteriaand VerrucomicrobiaIt is examined in 6 bacterial groups, including Bacteroidetesand Firmicuteson the other hand, they constitute 90% of the intestinal microbiota (10).

Bowel Role of Microbiota

Microbiomes have many benefits to the host. It has important roles in enzymatic reactions, host homeostasis, micronutrient synthesis, detoxification, epithelial development and immune system. One of the most important tasks of the microbiota is to provide efficient calories from the nutrients taken. For example, short-chain fatty acid (SCFA) is formed by fermentation from consumed and indigestible polysaccharides. This is observed by providing 100 kcal more calories than the daily diet. The microbiota also produces vitamin K, various B vitamins, H2, CO2, methane gas, lysine, and ammonia-urea conversion. It also plays a role in metabolizing ingested foreign compounds (xeno-biotics) and regulating the enterohepatic circulation of compounds that are detoxified by the liver and excreted with bile. Microbiomes stimulate the growth of enterocytes and help the development of the immune system (11,12).

Allergy, celiac disease, gastric cancer, autism, obesity, type 2 diabetes, rheumatoid arthritis, type 1 diabetes, hypertension, metabolic syndrome, mood disorder, irritable bowel disease (IBS) diseases are associated with the deterioration of the intestinal microbiota balance (9, 13).

Insulin Resistance and Gut Microbiota

The human gut microbiota is an important factor in the pathogenesis of obesity and insulin resistance. Microbiota has the task of maintaining and regulating metabolic order. It plays a role in glucose and lipid metabolism. Nowadays, intestinal dysbiosis is important for understanding the pathophysiology of obesity and diabetes (14).

Obesity, insulin resistance, and diabetes are associated with increased permeability of the bacterial composition in the intestinal lumen, which causes an unbalanced settling in the bloodstream and tissues. It causes changes in intestinal barrier activity with the increase of lipopolysaccharide (LPS) (gram negative bacteria) in the cell membrane. It has been shown that the increase in plasma LPS level, defined as metabolic endotoxemia, triggers insulin resistance, obesity and type 2 diabetes, and a small amount of inflammation and metabolic disorders. Mechanisms explaining the effect of microbiota on insulin resistance and Type 2 diabetes; metabolic endotoxemia, changes in incretin secretion and butyrate production (15,16).

In particular, the dysbiotic gut structure may trigger a chronic mild inflammation that sensitizes the host to systemic LPS exposure. Produced from the outer membrane of gram-negative bacteria, this large glycolipid molecule is the initiator of the innate immune system response associated with adiposity, insulin resistance, and de novo synthesis of triglycerides. LPS binds to TLR4 (toll-like receptor 4) and its co-receptors and initiates a series of reactions, resulting in the release of proinflammatory cytokines that are involved in the regulation of glucose and insulin metabolism (14, 17).

Studies have been conducted on the application of isolated butyrate, which has a protective feature against insulin resistance and obesity, by activating the existing pathways with SCFAs produced by the healthy microbiota from dietary polysaccharides. Experimental studies with butyrate have shown improvements in insulin sensitivity and brown adipose tissue accumulation (18). E. Halliihas been shown to have a positive effect on insulin sensitivity (19, 20).

Diabetes and Gut Microbiota

Genetic predisposition, obesity, visceral adiposity, chronic inflammation, insulin resistance, metabolic syndrome, β-cell defect are the main causes in the pathogenesis of Type 2 Diabetes. The increase in high-calorie food intake and the decrease in physical activity are the main reasons for the emergence of the disease. The results obtained in recent years indicate that the intestinal microbiota has an important role in the development of Type 2 Diabetes (16, 21).

Fermentation of indigestible carbohydrates alters the structure of the gut microbiota and also increases its activity, helping to regulate the bioactive metabolites that are released into the circulation. Fermentation of prebiotics aids in SCFA production. In addition to being produced by fermentation of prebiotics, SCFAs can also be formed as a result of digestion of complex carbohydrates. These metabolites affect insulin sensitivity and energy metabolism, and the central nervous system through many physiological pathways. Essentially, these metabolites alter the levels of several intestinal hormones such as GLP-1, GLP-2, GIP and NPY, which are involved in glucose and energy metabolism, stimulating insulin secretion and lowering blood glucose levels (22, 23).

In a study by Zhang et al., the subjects were divided into three groups as Type 2 diabetes, prediabetes (preDM) and normal glucose tolerance (NGT), and it was determined that the gut microbiota of each group was different. In the NGT group, compared to the prediabetes group, butyrate-producing Akkermansia Muciniphilaand Faecalibacterium prausnitziifound to be more. Verrucomicrobia , prediabetes Type 2 diabetes groups were found to be less than in the NGT group. According to these results, in addition to the fact that the gut microbiota of Type 2 diabetes patients is different from that of healthy individuals, changes in the microbiota are also associated with the progression of glucose intolerance (24).

Type 1 Diabetes is an autoimmune disease characterized by immune cell-mediated destruction of insulin-secreting pancreatic beta cells in genetically susceptible individuals as a result of environmental stimulation. The interaction between pancreatic β-cells and immune cells causes the development of Type 1 Diabetes. It is stated that environmental factors are effective in the development and different stages of Type 1 Diabetes. In addition, environmental factors are also effective in the emergence of Type 1 Diabetes. Environmental triggers of Type 1 Diabetes are infection and nutritional factors (22, 23).

He says that the gut microbiota acts as an “organ” with important functions in many metabolic events, systemic and mucosal immune system functions. The normal human intestinal microbiota has a mixed and healthy composition of microorganisms in the amount of 100-160 trillion. This process, which starts from birth, becomes specific to the individual with advancing age. The intestinal microbiota, different environmental factors, nutritional changes and dietary differences, and the drugs used, especially antibiotics, affect the intestinal microbiota negatively and create dysbiosis (unhealthy flora), creating a relationship with or outside the gastrointestinal tract. causes many diseases (25).

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