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.
"It has been hypothesized that beneficial microbes or probiotics can protect against diabetes ( Neu et al . , 2010 ) . VSL#3 has been shown to prevent diabetes in NOD mice when administered after weaning ( Calcinaro et al . , 2005 ) . Yet , admin - istration to germ - free NOD neonatal mice shows no effect ( Yurkovetskiy et al . , 2013 ) . Although NOD mice were deficient in several beneficial microbes present in the probiotic VSL#3 , we found that "
[Show abstract][Hide abstract] ABSTRACT: Accumulating evidence supports that the intestinal microbiome is involved in Type 1 diabetes (T1D) pathogenesis through the gut-pancreas nexus. Our aim was to determine whether the intestinal microbiota in the non-obese diabetic (NOD) mouse model played a role in T1D through the gut. To examine the effect of the intestinal microbiota on T1D onset, we manipulated gut microbes by: (1) the fecal transplantation between non-obese diabetic (NOD) and resistant (NOR) mice and (2) the oral antibiotic and probiotic treatment of NOD mice. We monitored diabetes onset, quantified CD4+T cells in the Peyer's patches, profiled the microbiome and measured fecal short-chain fatty acids (SCFA). The gut microbiota from NOD mice harbored more pathobionts and fewer beneficial microbes in comparison with NOR mice. Fecal transplantation of NOD microbes induced insulitis in NOR hosts suggesting that the NOD microbiome is diabetogenic. Moreover, antibiotic exposure accelerated diabetes onset in NOD mice accompanied by increased T-helper type 1 (Th1) and reduced Th17 cells in the intestinal lymphoid tissues. The diabetogenic microbiome was characterized by a metagenome altered in several metabolic gene clusters. Furthermore, diabetes susceptibility correlated with reduced fecal SCFAs. In an attempt to correct the diabetogenic microbiome, we administered VLS#3 probiotics to NOD mice but found that VSL#3 colonized the intestine poorly and did not delay diabetes. We conclude that NOD mice harbor gut microbes that induce diabetes and that their diabetogenic microbiome can be amplified early in life through antibiotic exposure. Protective microbes like VSL#3 are insufficient to overcome the effects of a diabetogenic microbiome.The ISME Journal advance online publication, 14 August 2015; doi:10.1038/ismej.2015.114.
The ISME Journal 08/2015; DOI:10.1038/ismej.2015.114 · 9.30 Impact Factor
"is rapidly gaining importance in clinical research        , environmental studies    and biotechnology   . 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    and MG-RAST  , the marker-gene identifying phylogenetic analyzer AMPHORA  and its more user-friendly versions, AMPHORA2  and AmphoraNet  . "
[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.
[Show abstract][Hide abstract] ABSTRACT: The worldwide obesity epidemic is paralleled by a rise in the incidence of pancreatic disorders ranging from "fatty" pancreas to pancreatitis and cancer. Body fat accumulation and pancreatic dysfunctions have common pathways, mainly acting through insulin resistance and low-grade inflammation, frequently mediated by the epigenome. These mechanisms are affected by lifestyle and by the toxic effects of fat and pollutants. An early origin is common, starting in pediatric age or during the fetal life in response to nutritional factors, endocrine disruptor chemicals (EDCs) or parental exposure to toxics. A "fatty pancreas" is frequent in obese and is able to induce pancreatic damage. The fat is a target of EDCs and of the cytotoxic/mutagenic effects of heavy metals, and is the site of bioaccumulation of lipophilic and persistent pollutants related with insulin resistance and able to promote pancreatic cancer. Increased Body Mass Index (BMI) can act as independent risk factor for a more severe course of acute pancreatitis and obesity is also a well-known risk factor for pancreatic cancer, that is related with BMI, insulin resistance, and duration of exposure to the toxic effects of fat and/or of environmental pollutants. All these mechanisms involve gene-environment interactions through epigenetic factors, and might be manipulated by primary prevention measures. Further studies are needed, pointing to better assess the interplays of modifiable factors on both obesity and pancreatic diseases, and to verify the efficacy of primary prevention strategies involving lifestyle and environmental exposure to toxics
European Journal of Internal Medicine 12/2014; 25(10):865-873. DOI:10.1016/j.ejim.2014.10.012 · 2.89 Impact Factor
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