scholarly journals Integrated multi-omics of the human gut microbiome in a case study of familial type 1 diabetes

2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Anna Heintz-Buschart ◽  
Patrick May ◽  
Cédric C. Laczny ◽  
Laura A. Lebrun ◽  
Camille Bellora ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Human Health ◽  
Large Scale ◽  
Integrative Approach ◽  
Gastrointestinal Microbiota ◽  
Gastrointestinal Microbiome ◽  
Familial Type ◽  
Microbe Interactions ◽  
Host Microbe Interactions

Abstract The gastrointestinal microbiome is a complex ecosystem with functions that shape human health. Studying the relationship between taxonomic alterations and functional repercussions linked to disease remains challenging. Here, we present an integrative approach to resolve the taxonomic and functional attributes of gastrointestinal microbiota at the metagenomic, metatranscriptomic and metaproteomic levels. We apply our methods to samples from four families with multiple cases of type 1 diabetes mellitus (T1DM). Analysis of intra- and inter-individual variation demonstrates that family membership has a pronounced effect on the structural and functional composition of the gastrointestinal microbiome. In the context of T1DM, consistent taxonomic differences were absent across families, but certain human exocrine pancreatic proteins were found at lower levels. The associated microbial functional signatures were linked to metabolic traits in distinct taxa. The methodologies and results provide a foundation for future large-scale integrated multi-omic analyses of the gastrointestinal microbiome in the context of host–microbe interactions in human health and disease.

scholarly journals Understanding the host-microbe interactions using metabolic modeling

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jack Jansma ◽  
Sahar El Aidy
Keyword(s):  
Human Health ◽  
Flux Balance Analysis ◽  
Bacterial Species ◽  
Flux Balance ◽  
Interaction Field ◽  
In Silico Simulation ◽  
Balance Analysis ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Genome Scale

AbstractThe human gut harbors an enormous number of symbiotic microbes, which is vital for human health. However, interactions within the complex microbiota community and between the microbiota and its host are challenging to elucidate, limiting development in the treatment for a variety of diseases associated with microbiota dysbiosis. Using in silico simulation methods based on flux balance analysis, those interactions can be better investigated. Flux balance analysis uses an annotated genome-scale reconstruction of a metabolic network to determine the distribution of metabolic fluxes that represent the complete metabolism of a bacterium in a certain metabolic environment such as the gut. Simulation of a set of bacterial species in a shared metabolic environment can enable the study of the effect of numerous perturbations, such as dietary changes or addition of a probiotic species in a personalized manner. This review aims to introduce to experimental biologists the possible applications of flux balance analysis in the host-microbiota interaction field and discusses its potential use to improve human health.

Analysis of a non-functional HNF-1? (TCF1) mutation in Japanese subjects with familial type 1 diabetes

2001 ◽  
Vol 18 (4) ◽  
pp. 345-351 ◽  
Author(s):  
Issei Yoshiuchi ◽  
Kazuya Yamagata ◽  
Masaaki Yoshimoto ◽  
Qian Zhu ◽  
Qin Yang ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Familial Type ◽  
Japanese Subjects

scholarly journals Characteristics of familial type 1 diabetes: effects of the relationship to the affected family member on phenotype and genotype at diagnosis

Diabetologia ◽  
2019 ◽  
Vol 62 (11) ◽  
pp. 2025-2039 ◽  
Author(s):  
Maaret Turtinen ◽  
◽  
Taina Härkönen ◽  
Anna Parkkola ◽  
Jorma Ilonen ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Family Member ◽  
Affected Family Member ◽  
Familial Type ◽  
The Relationship

Prospects of antigen-specific therapy in type 1 diabetes mellitus

2012 ◽  
Vol 15 (4) ◽  
pp. 28-32
Author(s):  
Tatiana Vasil'evna Nikonova ◽  
Yulia Viktorovna Alekseeva
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Pancreatic Beta Cells ◽  
Large Scale ◽  
Specific Immunotherapy ◽  
Preventive Measures ◽  
Therapeutic Agents ◽  
Specific Therapy

Type 1 diabetes mellitus is commonly recognized as an autoimmune disease characterized by progressive destruction of pancreatic ?-beta-cells. Progress in diagnostics at preclinical stage is accompanied with active development of preventive measures. So far, there are no specific therapeutic agents approved for clinical practice. However, ongoing large-scale studies have outlined some promising solutions, antigen-specific immunotherapy being one of them.

scholarly journals Monogenic causes in the Type 1 Diabetes Genetics Consortium cohort; low genetic risk for autoimmunity in case selection

2021 ◽  
Author(s):  
Luc Marchand ◽  
Meihang Li ◽  
Coralie Leblicq ◽  
Ibrar Rafique ◽  
Tugba Alarcon-Martinez ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Genetic Risk ◽  
Large Scale ◽  
Wolfram Syndrome ◽  
Monogenic Diabetes ◽  
Therapeutic Implications ◽  
Pathogenic Variants ◽  
Affected Parent ◽  
Diabetes Genetics

Abstract: Hypothesis About 1% of patients clinically diagnosed as type 1 diabetes have non-autoimmune monogenic diabetes. The distinction has important therapeutic implications but, given the low prevalence and high cost of testing, selecting patients to test is important. We tested the hypothesis that low genetic risk for type 1 diabetes can substantially contribute to this selection. Methods As proof of principle, we examined by exome sequencing families with two or more children, recruited by the Type 1 Diabetes Genetics Consortium and selected for negativity for two autoantibodies and absence of risk HLA haplotypes. Results We examined 46 families that met the criteria. Of the 17 with an affected parent, seven (41.2%) had actionable monogenic variants. Of 29 families with no affected parent, 14 (48.3%) had such variants, including five with recessive pathogenic variants of WFS1 but no report of other features of Wolfram syndrome. Our approach diagnosed 55.8% of the estimated number of monogenic families in the entire T1DGC cohort, by sequencing only 11.1% of the autoantibody-negative ones. Conclusions Our findings justify proceeding to large-scale prospective screening studies using markers of autoimmunity, even in the absence of an affected parent. We also confirm that non-syndromic WFS1 variants are common among cases of monogenic diabetes misdiagnosed as type 1 diabetes.

scholarly journals Fatigue Among Adults With Type 1 Diabetes Mellitus and Implications for Self-Management: An Integrative Review

2018 ◽  
Vol 44 (4) ◽  
pp. 325-339 ◽  
Author(s):  
Stephanie Griggs ◽  
Nancy S. Morris
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Secondary Data ◽  
Sociodemographic Factors ◽  
Small Samples ◽  
Integrative Approach ◽  
Cross Sectional ◽  
Qualitative Phenomenology

Purpose The aim of this review was to integrate empirical and theoretical literature on fatigue among adults with type 1 diabetes mellitus (T1DM). A methodological review using an integrative approach was used. Databases MEDLINE via Pubmed, CINAHL, PsycINFO, and Science Direct were searched for peer-reviewed articles published in English from 2007-2017, using the following search terms and Boolean operators: “Type 1 Diabetes” and “Fatigue.” Of 199 articles initially retrieved, 14 were chosen for inclusion. These articles included 13 quantitative (7 cross-sectional, 2 cohort, 2 secondary data analyses, 2 experimental) and 1 qualitative phenomenology. Fatigue was identified as one of the most troublesome symptoms reported in persons with T1DM. Four main themes emerged: fatigue in T1DM is multidimensional and related to psychological, physiological, situational, and sociodemographic factors. Conclusions Fatigue is considered a classic symptom of hyperglycemia; however, there were minimal data to support the theory that fatigue is related to hyperglycemia or hypoglycemia. Studies on fatigue among persons with T1DM are limited to small samples and cross-sectional designs with few randomized controlled trials addressing fatigue and diabetes-related symptoms. Evidence is conflicting regarding the onset of fatigue among persons with T1DM and the relationship between fatigue and diabetes duration. The prevalence of fatigue is likely influenced by disease physiology, psychological stress, and lifestyle factors, but more research is needed to confirm these relationships as causal inference is unclear.

scholarly journals Gastrointestinal Microbiota and Type 1 Diabetes Mellitus: The State of Art

2019 ◽  
Vol 8 (11) ◽  
pp. 1843 ◽  
Author(s):  
Marilena Durazzo ◽  
Arianna Ferro ◽  
Gabriella Gruden
Keyword(s):  
Type 1 Diabetes ◽  
Disease Onset ◽  
Future Perspectives ◽  
Gastrointestinal Microbiota ◽  
Pathogenic Role ◽  
Negative Results ◽  
Intestinal Dysbiosis ◽  
Younger Age ◽  
Exciting Area

The incidence of autoimmune type 1 diabetes (T1DM) is increasing worldwide and disease onset tends to occur at a younger age. Unfortunately, clinical trials aiming to detect predictive factors of disease, in individuals with a high risk of T1DM, reported negative results. Hence, actually there are no tools or strategies to prevent T1DM onset. The importance of the gut microbiome in autoimmune diseases is increasingly recognized and recent data suggest that intestinal dysbiosis has a pathogenic role in T1DM by affecting both intestinal immunostasis and the permeability of the gut barrier. An improved understanding of the mechanisms whereby dysbiosis in the gut favors T1DM development may help develop new intervention strategies to reduce both the incidence and burden of T1DM. This review summarizes available data on the associations between gut microbiota and T1DM in both experimental animals and humans and discusses future perspectives in this novel and exciting area of research.

scholarly journals The Association between rs2292239 Polymorphism in ERBB3 Gene and Type 1 Diabetes: A Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Dingjian Wang ◽  
Guixia Pan
Keyword(s):  
Type 1 Diabetes ◽  
Large Scale ◽  
Web Of Science ◽  
Meta Analysis ◽  
Cochrane Library ◽  
P Value ◽  
Case Control Studies ◽  
Heterogeneity Test ◽  
Strength Of Association

Objectives. The purpose of this study was to explore the association between rs2292239 polymorphism in ERBB3 gene and type 1 diabetes (T1D). Methods. A systematic search of studies on the association of rs2292239 polymorphism in ERBB3 gene with T1D susceptibility was conducted in PubMed, Web of science, Elsevier Science Direct, and Cochrane Library. Eventually, 9 published studies were included. The strength of association between rs2292239 polymorphism and T1D susceptibility was assessed by odds ratios (ORs) with its 95% confidence intervals (CIs). Results. A total of 9 case-control studies, consisting of 5369 T1D patients and 6920 controls, were included in the meta-analysis. This meta-analysis showed significant association between ERBB3 rs2292239 polymorphism and T1D susceptibility in overall population (A vs. C, OR: 1.292, 95% CI= 1.224-1.364, PH=0.450, PH is P value for the heterogeneity test). Similar results were found in subgroup analysis by ethnicity. Conclusions. ERBB3 rs2292239 polymorphism is associated with T1D susceptibility and rs2292239-A allele is a risk factor for T1D. However, more large-scale studies are warranted to replicate our findings.

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