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

详细信息    查看全文

• 作者：Fraser W. Scott^a ; ^b ; ^c ; ^{fscott@ohri.ca} ; Lynley D. Pound^a ; Christopher Patrick^a ; Chandra E. Eberhard^a ; ^b ; Jennifer A. Crookshank^a
• 关键词：BBdp ; BioBreeding Diabetes-prone (rat) ; CAMP ; cathelicidin antimicrobial peptide ; CD14 ; cluster of differentiation 14 ; CD163 ; cluster of differentiation 163 ; CRAMP ; cathelicidin-related antimicrobial peptide ; CCL2 ; C-C Motif Chemokine Ligand 2 ; CCL5 ; C-C Motif Chemokine Ligand 5 ; CCL3 ; C-C Motif Chemokine Ligand 3 ; cMLN ; colonic mesenteric lymph nodes ; CTLA4 ; Cytotoxic T-lymphocyte associated antigen 4 ; CXCL9 ; Chemokine (C-X-C motif) ligand 9 ; CXCL10 ; Chemokine (C-X-C motif) ligand 10 ; CXCL11 ; C
• 刊名：Translational Research
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：179
• 期：Complete
• 页码：183-198
• 全文大小：1073 K
• 卷排序：179

文摘

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. Most 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.