Microbiota, Dysbiosis and Risk of Disease PDF

Microbiota & Dysbiosis Risk of Disease Pınar Yurdakul-Mesutoğlu, Prof Department of Medical Microbiology Heathy or not? Dysbiosis Diet and other environmental factors Atb Hospitalization Co-morbid factors S...

Microbiota & Dysbiosis Risk of Disease Pınar Yurdakul-Mesutoğlu, Prof Department of Medical Microbiology Heathy or not? Dysbiosis Diet and other environmental factors Atb Hospitalization Co-morbid factors Serra Yaşasın Şeyma Tekintaş Obesity-Microbiota Dysbiosis In recent years, there has been considerable amount of studies, which are not very strong in terms of evidence, but that the state of the GI microbiota may be related to the biology of adipocytes, inflammation and insulin resistance, especially due to the increased amount of fat in the body Obesity-Mechanism Dysbiosis in the intestinal microbiota increase in gut permeability, fluctuations in the production of SCFA  change in glucose and lipd metabolism, inflammation and metabolic endotoxemia obesity  Million et al, in obese persons: It was determined that the rate of Bacteroidetes was similar, the rate of Firmicutes increased, and the rate of Bifidobacterium decreased Microbiota-diet-obesity: high fat diet When the fat content of the diet is high, the mucosal integrity of the intestinal epithelial wall is impaired. Deterioration of mucosal integrity in the intestine causes an increase in intestinal epithelial permeability (permeability) and an increase in plasma lipopolysaccharide (LPS) levels. Increased plasma LPS level leads to metabolic endotoxemia and increased basal inflammation. The increase in inflammation in the body paves the way for the emergence of metabolic diseases. Microbiota-diet-obesity: high protien diet Proteins in the intestinal microbiota undergo fermentation just like carbohydrates. However, only 10% of dietary protein reaches the colon and can be fermented. Fermentable proteins are converted into various metabolic products. Ammonia, ethanol, organic acids and hydrogen sulphate are some of the metabolic products formed. It is thought that these metabolic products, which are formed as a result of the high protein content of the diet, may cause colorectal cancer, inflammatory bowel disease and atherosclerosis. 1. 5 fundemental Phyla in the gut: Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Verrucomicrobia 2. Increase in the ration of Firmicutes/Bacterioidetes is linked to obesity 3. Lactobacillus reuteri!! 4. Fusobacteria 5. Faecalibacterium prausnitzii** & Akkermansia muciniphila** Sonuç XR, farnesoid X receptor; GLP-1, glucagon-like peptide; LPS, lipopolysaccharide; SCFAs, short-chin fatty acids; TGR5, G-protein-coupled bile acid receptor 1.Gut microbiome in obesityS5 Effect of Microbiota Changes in nutrient and energy intake CH and lipid metabolism and Bile acid metabolism; SCFA: Glucose balance, insulin sensitivity, satiety hormone intestinal barrier functionlipid met effects PYY hormone --fullness Effect of Microbiota Antibiotics and Dysbiosis Hormones and neurotransmitter secretion: Firmicutes species (Clostridium, Eubacterium rectale, Clostridium coccoides, Lactobacillus reuteri, A. muciniphila, Clostridium histolyticum, ve Staphylococcus aureus gastrin, cholecystokinin, somatostatin, and ghrelinproblems related to feeling of fullness and over eating Microbiota- Firmicutes/Bacteriodetes Pro-Prebiotics and Obesity Probiotic--reduced adipose tissue and reduced pro-inflammatory cytokines were found Two-week prebiotic supplementation has been shown to improve microbiota fermentation, reduce appetite, and improve postprandial glucose response in humans. Lee HY, Park JH, Seok SH, et al. Human originated bacteria, Lactobacillus rhamnosus PL60, produce conjugated linoleic acid and show anti-obesity effects in diet-induced obese mice. Biochim Biophys Acta 2006; 1761:736–744. 38. Cani PD, Lecourt E, Dewulf EM, et al. Gut microbiota fermentation of prebiotics increases satietogenic and incretin gut peptide production with consequences for appetite sensation and glucose response after a meal. Am J Clin Nutr 2009; 90:1236–1243. Type 2 Diabetes (T2D)- Microbiota Dysbiosis Microbiota-T2D  Dysbiosis can trigger an autoimmune process resulting in increased intestinal permeability, disruption of immune regulatory mechanisms, and destruction of beta cells in pancreatic islets  Similarly, saturated fats and dysbiosis triggered by an obesogenic diet may contribute to the development of type 2 diabetes through increased intestinal permeability and inflammatory response Microbiota-T2D & Dysbiosis Increase in Gram (-) LPS TLR-4 binding Metabolic endotoxemia Increase in IL-1, IL-6 ve TNF alpha levels— trigger inflammation lipogenesis and mQ infiltration Dysfunction in gut barrier function Insulin resistance  Microbiota-T2D & Short Chain Fatty Acids (SCFA): Butyrate Serra Yaşasın  Microbiota-T2D Serra Yaşasın Microbiota-Type 2 DM Metagenomic studies from Europe have produced data, supporting that changes in the composition and function of the human gut microbiota may be associated with adiposity, insulin resistance, and type 2 diabetes. Microbiota-T2D Akkermansia muciniphila**critical: Metabolic endotoxemia and inflammation and increase in insulin resistance Roseburia Faecalibacterium prausnitzii  Microbiota-T2D In addition to increased absorption of macromolecules and changes in glucose and lipid metabolism as a result of increased intestinal permeability, 3 main molecules are considered critical: LPS, SCFA and bile acids Other diseases linked to dysbiosis Metabolic syndrome Cardiovascular diseases T1D Non alcoholic liver disease Microbiota-T1D In studies where the composition of the microbiota was evaluated, colonization or antibiotics were applied, intestinal microbiota changes were associated with the development of type 1 diabetes. It has been shown that modulation of microbiota by applying protective intestinal flora transfer can delay or prevent the development of type 1 diabetes  T1D: SCFA SCFA  Bifidobacterium, Lactobacillus, Ruminococcus, Clostridium, Faecalibacterium Butyrate contributes to colon health and prevents leaky gut syndrome with its anti-inflammatory properties and reducing bacterial migration to epithelial cells.  Otoimmünite ve tip 1 diyabet (T1D) gelişiminde diyet ve mikrobiyota ile ilişkili mekanizmalar. Nutrients. 2015 Nov; 7(11): 9171–9184. Published online 2015 Nov 6. doi: 10.3390/nu7115461 The relationship between T1D and dysbiosis in the lactate model: According to this model, the presence of lactic acid and butyrate producing bacteria such as Prevotella and Akkermansia helps maintain a healthy epithelium. This is because butyrate contributes to mucin synthesis and thus to the intestinal epithelium. These bacteria were common in the microbiota of healthy children worldwide.. Conversely, when microorganisms such as Bacteroides and Veillonella are abundantly present, these bacteria follow the path to succinate, acetate and propionate. These products compromise mucin synthesis and alter tight junctions, increasing intracellular permeability Microbiota and Cancer When two populations living in peace and solidarity are threatened for various reasons, "symbiosis" turns into "dysbiosis", and peaceful bacteria turn into "pathobionts" that cause disease. Prof. Dr. Nurdan Tüzün TÜBA Mikrobiyota İnsan Sağlığı Sempozyumu  Microbiota & Cancer Inflammation triggered by the microbiome also causes cancer by stimulating many cytokines and chemokines that increase cell proliferation and suppress apoptosis Diet: The foods we take are important in terms of both the microbiota content and the development of cancer. Namely, the products of microbial metabolism contribute to the development of cancer Prof. Dr. Nurdan Tüzün TÜBA Mikrobiyota İnsan Sağlığı Sempozyumu Aging and Microbiota Hypothesis related to chronic aging Human lifespan is shaped as a result of a complex process involving many genetic and environmental factors, and very few individuals have the chance to reach the age of 100 and above. Telomere hypothesis: Long telomere presence is associated with longevity Number of mitochondria-SASP presence Microbiota diversity-inflammaging: inflammatory cytokine increase  Kostic AD et al. In their study in 2013, Bacteroides, Firmicutes and Acinetobacter from 3 main bacterial families Significant change from childhood to advanced age. Increase in Bacteroides group and decrease in Firmicutes group with age Wu et al. Western diet was associated with Bacteroides, and a Mediterranean diet containing vegetables and fiber was associated with Firmicutes group bacteria.  Odamaki et al. They examined changes in the gut microbiota from newborn to advanced age, and similar to previous study data:  They detected a decrease in Firmicutes group bacteria, an increase in Bacteroides group bacteria, a decrease in Actinobacteria, and an increase in Proteobacteria.  O'Toole PW et al. Eldermet Cohort study by Eldermet Cohort Increase in Bacteroides group in frail elderly The most affected bacterial gene with advanced age is the Prevotella group. It was found to be significantly reduced in those staying in the nursing home for a long time. Sentanaryanları içeren bir çalışmada: They found that SCFA metabolism decreased, aromatic amino acid catabolism increased, and pathobiota (pro-inflammatory cytokine-releasing bacteria) decreased in these individuals ( Rampelli et al.) Park ve ark. They evaluated the elderly people living in the city and in the villages where long-lived people live in terms of microbiota diversity. The most important difference is that Prevotella is more pronounced in long-lived people living in the village. Again, the amount of fecal endotoxin is significantly lower in this group of elderly compared to those living in the city. Who live healthy and long lives.. Prevotella, Firmicute and Ruminococcaceae increase, Lachnospiraceae decrease, Bacteroides inrease is not prominent For healthy longevity, it is necessary not only to reveal the diversity of bacteria, but also to examine the metabolite produced by these bacteria and the cytokine production to which they contribute. Inflammatory Bowel Diseases Ulcerative colitis and Crohn’s Protective mechanism Segmented filamentous bacteriaIL-1 and IL- 23Th17 stimulation Mucosal defense integrity-IgA expression Akkermansia**--secretion of homeostatic IgG Therapeutic approaches IBS-mechanisms IBS F/B ratio should be ½ IBS—Firmicutes increase  4-5