Epigenetic Regulation in Etiology of Type 1 Diabetes Mellitus

Černá, Marie

doi:10.3390/ijms21010036

Cited by 51 publications

(43 citation statements)

References 62 publications

(70 reference statements)

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“…Also, the same study showed a decrease in the level of the hypermethylated FOXP3 promoter in CD4+ T cells of LADA patients compared with controls; a biomarker of T1D (37). On the other hand, many studies showed variation of DNA methylation within the insulin region (INS), which represent the second most important locus associated with T1D (38)(39)(40)(41)(42). In fact, the variation of the DNA methylation within the INS gene is suspected to regulate INS gene transcription in the pancreatic β-cells as well as the medullary thymic epithelial cells.…”

Section: Epigenetics In T1dmentioning

confidence: 89%

Epigenetic Effects of Gut Metabolites: Exploring the Path of Dietary Prevention of Type 1 Diabetes

et al. 2020

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Type 1 diabetes (T1D) has increased over the past half century and has now become the second most frequent autoimmune disease in childhood and one of major public health concern worldwide. Evidence suggests that modern lifestyles and rapid environmental changes are driving factors that underlie this increase. The integration of these two factors brings about changes in food intake. This, in turn, alters epigenetic regulations of the genome and intestinal microbiota composition, which may ultimately play a role in pathogenesis of T1D. Recent evidence shows that dysbiosis of the gut microbiota is closely associated with T1D and that a dietary intervention can influence epigenetic changes associated with this disease and may modify gene expression patterns through epigenetic mechanisms. In this review focus on how a diet can shape the gut microbiome, its effect on the epigenome in T1D, and the future of T1D management by microbiome therapy.

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Section: Epigenetics In T1dmentioning

confidence: 89%

Epigenetic Effects of Gut Metabolites: Exploring the Path of Dietary Prevention of Type 1 Diabetes

et al. 2020

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“…Up to 50% of genetic risk for T1DM is due to the presence of susceptibility loci within the human leukocyte antigen (HLA) regions ( 5 – 7 ), with a strong linkage between T1DM and genetic variations of the HLA region on the short arm of chromosome 6 (6p21) ( 4 – 6 , 8 , 9 ).…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota and Type 1 Diabetes Mellitus: The Effect of Mediterranean Diet

Calabrese

Valentini²,

Calabrese

2021

Front. Nutr.

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Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease resulting from a complex interplay between genetic susceptibility and environmental factors. Regarding the latter, gut microbiota has a pivotal role in the pathogenesis of T1DM, by affecting intestinal permeability, molecular mimicry, and modulating innate and adaptive immune system, as described in several previous studies. The composition of the gut microbiota is largely influenced by diet. Some observational studies have shown that a low fiber intake is associated with the development of many inflammatory and immune-mediated diseases. In this context, the Mediterranean diet (MD), which is based on high consumption of cereals (preferably as whole grains), legumes, nuts, vegetables, fruits, olive oil, and fish, could play a protective role. Many of the characteristic components of MD have functional characteristics with positive effects on health and well-being. Eating habits are the main significant determinants of the microbial multiplicity of the intestine and the food components influence both microbial populations and their metabolic activities from the early stages of life. Moreover, food metabolites influence the immune response. The intestine is considered the primary site where food metabolites mediate their effects, through epithelial integrity or mucosal immunity. The compromised epithelial integrity allows the translocation of bacteria and/or the diffusion of their products, such as food antigens and lipopolysaccharides, from the intestinal lumen to the tissues, which could enhance the stimulation of immune cells, contributing to the pathogenesis of autoimmune diseases, such as T1DM. The intake of a high amount of fiber and therefore of prebiotics with MD allows the microbiota to have a good microbial balance. Moreover, as more dietary fibers are ingested, a higher amount of short-chain fatty acids (SCFAs) is produced by anaerobic gut microbiota, promoting gut homeostasis, to which also contribute tryptophan metabolites and omega-3-fatty acids. Furthermore, the higher intake of polyunsaturated fatty acids and omega-3-fatty-acids contribute to a better metabolic control. In this review we report the relationship between gut microbiota and T1DM and we explore the effects of Mediterranean diet on microbiota as a potential therapeutic strategy, aimed at preventing or delaying progression of T1DM and its complications.

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“…Recently, a substantial increase in T1D incidence was observed [ 10 ], suggesting that multiple contributing factors must be involved in this higher incidence. Those factors include genetic and epigenetics contributors, autoimmunity, viral infections, antibiotics-mediated dysbiosis, gut microbiome composition, and lifestyle factors such as nutrition and modern diet [ 2 , 11 , 12 , 13 , 14 , 15 ]. Although certain HLA risk alleles are known to increase the susceptibility to T1D in children at risk, only 5% or fewer of them actually develop T1D [ 16 ], highlighting the importance of the non-genetic modifiers, in addition to other environmental factors in T1D pathogenesis [ 12 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Exploring the Triple Interaction between the Host Genome, the Epigenome, and the Gut Microbiome in Type 1 Diabetes

Elhag

Kumar

Khodor

2020

IJMS

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Type 1 diabetes (T1D) is an auto-immune disorder characterized by a complex interaction between the host immune system and various environmental factors in genetically susceptible individuals. Genome-wide association studies (GWAS) identified different T1D risk and protection alleles, however, little is known about the environmental factors that can be linked to these alleles. Recent evidence indicated that, among those environmental factors, dysbiosis (imbalance) in the gut microbiota may play a role in the pathogenesis of T1D, affecting the integrity of the gut and leading to systemic inflammation and auto-destruction of the pancreatic β cells. Several studies have identified changes in the gut microbiome composition in humans and animal models comparing T1D subjects with controls. Those changes were characterized by a higher abundance of Bacteroides and a lower abundance of the butyrate-producing bacteria such as Clostridium clusters IV and XIVa. The mechanisms by which the dysbiotic bacteria and/or their metabolites interact with the genome and/or the epigenome of the host leading to destructive autoimmunity is still not clear. As T1D is a multifactorial disease, understanding the interaction between different environmental factors such as the gut microbiome, the genetic and the epigenetic determinants that are linked with the early appearance of autoantibodies can expand our knowledge about the disease pathogenesis. This review aims to provide insights into the interaction between the gut microbiome, susceptibility genes, epigenetic factors, and the immune system in the pathogenesis of T1D.

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Epigenetic Regulation in Etiology of Type 1 Diabetes Mellitus

Cited by 51 publications

References 62 publications

Epigenetic Effects of Gut Metabolites: Exploring the Path of Dietary Prevention of Type 1 Diabetes

Epigenetic Effects of Gut Metabolites: Exploring the Path of Dietary Prevention of Type 1 Diabetes

Gut Microbiota and Type 1 Diabetes Mellitus: The Effect of Mediterranean Diet

Exploring the Triple Interaction between the Host Genome, the Epigenome, and the Gut Microbiome in Type 1 Diabetes

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