Article

The Intestinal Microbiome: Relationship to Type 1 Diabetes

Department of Pediatrics, University of Florida, Gainesville, FL 326101, USA.
Endocrinology and metabolism clinics of North America (Impact Factor: 2.86). 09/2010; 39(3):563-71. DOI: 10.1016/j.ecl.2010.05.008
Source: PubMed

ABSTRACT This article discusses recent evidence that associates the developing intestinal microbiome to the pathogenesis of autoimmune T1D. It attempts to identify avenues that should be pursued that relate this new evidence to interventions that eventually could result in prevention.

2 Followers
 · 
175 Views
  • Source
    • "is rapidly gaining importance in clinical research [2] [3] [4] [5] [6] [7] [8] [9], environmental studies [10] [11] [12] and biotechnology [13] [14] [15]. Numerous complex and reliable methods have been published for the phylogenetic identification of non-cloned short DNA reads from environmental or clinical samples, for example, the similarity-based methods MEGAN [16] [17] [18] and MG-RAST [19] [20], the marker-gene identifying phylogenetic analyzer AMPHORA [21] and its more user-friendly versions, AMPHORA2 [22] and AmphoraNet [23] [24]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Discoveries of new biomarkers for frequently occurring diseases are of special importance in today's medicine. While fully developed type II diabetes (T2D) can be detected easily, the early identification of high risk individuals is an area of interest in T2D, too. Metagenomic analysis of the human bacterial flora has shown subtle changes in diabetic patients, but no specific microbes are known to cause or promote the disease. Moderate changes were also detected in the microbial gene composition of the metagenomes of diabetic patients, but again, no specific gene was found that is present in disease-related and missing in healthy metagenome. However, these fine differences in microbial taxon- and gene composition are difficult to apply as quantitative biomarkers for diagnosing or predicting type II diabetes. In the present work we report some nucleotide 9-mers with significantly differing frequencies in diabetic and healthy intestinal flora. To our knowledge, it is the first time such short DNA fragments have been associated with T2D. The automated, quantitative analysis of the frequencies of short nucleotide sequences seems to be more feasible than accurate phylogenetic and functional analysis, and thus it might be a promising direction of diagnostic research.
  • Source
    • "Bosi et al. (2006) observed increased gut permeability in human subjects with type 1 diabetes . Because gut microbes can affect intestinal permeability (Garcia-Lafuente et al. 2001), gut ecology may play a role in the development of type 1 diabetes (Neu et al. 2010). Another hypothesis by which microbes may cause type 1 diabetes is by producing bacterial toxins that can directly damage or affect the function of pancreatic beta cells. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Gut mucosal barrier breakdown and inflammation have been associated with high levels of flagellin, the principal bacterial flagellar protein. Although several gut commensals can produce flagella, flagellin levels are low in the healthy gut, suggesting the existence of control mechanisms. We find that mice lacking the flagellin receptor Toll-like receptor 5 (TLR5) exhibit a profound loss of flagellin-specific immunoglobulins (Igs) despite higher total Ig levels in the gut. Ribotyping of IgA-coated cecal microbiota showed Proteobacteria evading antibody coating in the TLR5(-/-) gut. A diversity of microbiome members overexpressed flagellar genes in the TLR5(-/-) host. Proteobacteria and Firmicutes penetrated small intestinal villi, and flagellated bacteria breached the colonic mucosal barrier. In vitro, flagellin-specific Ig inhibited bacterial motility and downregulated flagellar gene expression. Thus, innate-immunity-directed development of flagellin-specific adaptive immune responses can modulate the microbiome's production of flagella in a three-way interaction that helps to maintain mucosal barrier integrity and homeostasis.
    Cell host & microbe 11/2013; 14(5):571-81. DOI:10.1016/j.chom.2013.10.009 · 12.19 Impact Factor
  • Source
    • "Bosi et al. (2006) observed increased gut permeability in human subjects with type 1 diabetes . Because gut microbes can affect intestinal permeability (Garcia-Lafuente et al. 2001), gut ecology may play a role in the development of type 1 diabetes (Neu et al. 2010). Another hypothesis by which microbes may cause type 1 diabetes is by producing bacterial toxins that can directly damage or affect the function of pancreatic beta cells. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Gut microbiota are important factors in obesity and diabetes, yet little is known about their role in the toxicodynamics of environmental chemicals, including those recently found to be obesogenic and diabetogenic. We integrated evidence that independently links gut ecology and environmental chemicals to obesity and diabetes, providing a framework for suggesting how these environmental factors may interact with these diseases, and identified future research needs. We examined studies with germ-free or antibiotic-treated laboratory animals, and human studies that evaluated how dietary influences and microbial changes affected obesity and diabetes. Strengths and weaknesses of studies evaluating how environmental chemical exposures may affect obesity and diabetes were summarized, and research gaps on how gut ecology may affect the disposition of environmental chemicals were identified. Mounting evidence indicates that gut microbiota composition affects obesity and diabetes, as does exposure to environmental chemicals. The toxicology and pharmacology literature also suggests that interindividual variations in gut microbiota may affect chemical metabolism via direct activation of chemicals, depletion of metabolites needed for biotransformation, alteration of host biotransformation enzyme activities, changes in enterohepatic circulation, altered bioavailability of environmental chemicals and/or antioxidants from food, and alterations in gut motility and barrier function. Variations in gut microbiota are likely to affect human toxicodynamics and increase individual exposure to obesogenic and diabetogenic chemicals. Combating the global obesity and diabetes epidemics requires a multifaceted approach that should include greater emphasis on understanding and controlling the impact of interindividual gut microbe variability on the disposition of environmental chemicals in humans.
    Environmental Health Perspectives 03/2012; 120(3):332-9. DOI:10.1289/ehp.1104204 · 7.03 Impact Factor
Show more