Where genes meet environment - Integrating the role of gut luminal contents, immunity and pancreas in type 1 diabetes

Abstract The rise in new cases of type 1 diabetes (T1D) in genetically susceptible individuals over the past half century has been attributed to numerous environmental “triggers” or promoters such as enteroviruses, diet and most recently, gut bacteria. No single cause has been identified in humans,...

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Published in:Translational research : the journal of laboratory and clinical medicine 2017-01, Vol.179, p.183-198
Main Authors: Scott, Fraser W, Pound, Lynley, Patrick, Christopher, Eberhard, Chandra, Crookshank, Jennifer
Format: Article
Language:English
Subjects:
Animals
Diabetes Mellitus, Type 1 - metabolism
Diabetes Mellitus, Type 1 - pathology
Gastrointestinal Tract - metabolism
Gene-Environment Interaction
Humans
Immunity - genetics
Internal Medicine
Models, Biological
Pancreas - metabolism
Pancreas - pathology
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Summary:Abstract The rise in new cases of type 1 diabetes (T1D) in genetically susceptible individuals over the past half century has been attributed to numerous environmental “triggers” or promoters such as enteroviruses, diet and most recently, gut bacteria. No single cause has been identified in humans, likely because there are several pathways by which one can develop T1D. There is renewed attention to the role of the gut and its immune system in T1D pathogenesis based largely on recent animal studies demonstrating that altering the gut microbiota affects diabetes incidence. Although T1D patients display dysbiosis in the gut microbiome it is unclear whether this is cause or effect. The heart of this question involves several moving parts including numerous risk genes, diet, viruses, gut microbiota, timing and loss of immune tolerance to β-cells. The majority of clinical trials have addressed only one aspect of this puzzle using some form of immune suppression, without much success. The key location where our genes meet and deal with the environment is the gastrointestinal tract. The influence of all of its major contents, including microbes, diet and immune system must be understood as part of the integrative biology of T1D before we can develop durable means of preventing, treating or curing this disease. In the present review we expand our previous gut centric model based on recent developments in the field.
ISSN:1931-5244
1878-1810
DOI:10.1016/j.trsl.2016.09.001