Aberrant gut microbiota composition at the onset of type 1 diabetes in young children

Introduction. RESEARCH DESIGN AND METHODS—A total of 145 young patients with early-onset diabetes (age and age at diagnosis ≤40 years) and a family history of diabetes were studied. A parent with MODY has a 50% chance of passing on MODY to their child. (14) “Overload” may be caused by a high growth rate in fetal and early life (15), or by early-life stress, such as complicated pregnancy (16), neonatal hospitalization, or even childhood psychological stress. Absolute mortality was significantly lower in females than in males (HR 0.50 [95% CI 0.38, 0.65]), although the SMRs were similar. Later age at onset of diabetes was associated with a higher rate of having a first child among men (p = 0.04) and having a second live birth among women (p = 0.002). Annually, in 1991-2009 the proportion presenting with ketoacidosis varied between 20% and 33% (mean 25%) with no change over time.

We designed and validated a diagnostic flowchart in the attempt to improve the detection rate and to increase the number of properly requested tests. Stoss et al. The rapid development of the gut microbiota during the first 3 years of life furthermore necessitates the use of paired analyses. Obesity is prevalent in youths with newly diagnosed diabetes, particularly during recent years. Furthermore, two diabetic children older than 3 years were missing a paired control (as a matching sample failed to produce results). In order to use as many data points as possible, Table 1 shows the results from the paired and unpaired analyses in both age cohorts. Clostridium clusters IV and XIVa were found to be similarly important in a recent study involving Finnish children that were positive for two or more diabetes-related autoantibodies, as several of their members were found to be negatively correlated with the number of diabetes-specific autoantibodies [11].

Newborn litters were treated during the first few days of life in the following way: the newborn pups were taken from their mother for two 4-h periods during each of 5 successive days. Finally, Hamman et al. Calcineurin inhibitors prevent beta-cells from making insulin efficiently and so the blood glucose may remain high and therefore lead to a diagnosis of diabetes. Fasting blood sugar (FBS) 114 mg/dL, HbA1c 6.5%. Proportions were compared between MODY groups using the Fisher’s exact test, and means and medians were compared using the Student’s t test and the Mann-Whitney U test, respectively, or the Kruskal-Wallis test. The association of Bacteroidetes with diabetes has been reported both in humans and in animal models [8–13], but the association between streptococci and type 1 diabetes has only been reported in a study that was also carried out in very young children [15]. Even though the prevalence of streptococci was negatively correlated with that of Bacteroidetes, they were also found to be more prevalent in the younger diabetic children.

Soft tissue infections with both streptococci and members of the Bacteroides fragilis group, as well as respiratory tract infections and bacteraemia associated with streptococci, are more common in diabetic patients [34, 35]. A possibly important similarity between Bacteroides and streptococci in their role in the development of type 1 diabetes is that they both produce glutamate decarboxylase, which might be the trigger for GAD autoimmunity via molecular mimicry [36]. This is performed with an oral glucose tolerance test. de Goffau, unpublished observations) [11]. Contrary to expectations, bifidobacteria were not found to be correlated with diabetes in this study of new-onset diabetes, even though they have previously been found to be negatively associated with beta cell autoimmunity in Finnish children with two or more diabetes-related autoantibodies aged 4–14 years [11], in 7-year-old Spanish diabetic patients [12] and in a Turkish study with even older diabetic children [37]. and C.C.P.) to establish whether the studies were likely to provide relevant data based on the following inclusion criteria: 1) they identified a group with type 1 diabetes and a group without type 1 diabetes, and 2) they recorded maternal age in these groups. In several studies of type 1 diabetes, the Prevotella genus has also been found to be more prevalent in controls [10, 12, 13], although this was not found in the present study.

The most logical reason for this is that Prevotella is simply rare in Finland even in healthy controls (0.6%). In the all-Finnish study by de Goffau et al, Prevotella was absent in 31 out of 36 children (M. Associated with kidney disease that is often diagnosed before diabetes. Because ten of the diabetic children were of non-Finnish origin whereas nearly all the control children were Finnish, it is critical to mention that the differences found between the diabetic and non-diabetic children with regard to the patterns related to Clostridium clusters IV and XIVa, as described in Fig. 3, have not been artificially introduced by possible differences in gut microbiota between Finland and the other European countries: analyses using only Finnish samples yield the same patterns. However, as non-Finnish diabetic children had a lower total abundance of non-butyrate-producing species from Clostridium clusters IV and XIVa, they had a higher abundance of several other groups, most importantly a higher abundance of the closely related Clostridium clusters I and XI [38, 39], which are found to be strongly negatively correlated with Bacteroides. As a relatively large proportion of the diabetic children older than 2.9 years did not come from Finland, this might have obfuscated the correlation between Bacteroides and type 1 diabetes in this age category.

As samples were sent at ambient temperatures before being stored at −75°C, it is not inconceivable that this might have had a small effect on the faecal microbial composition during transit [40, 41]. (2001) reported further details of the same patient. The causality and even the direction of causality of the changes in the microbial composition reported in this and other similar studies still need to be substantiated by functional studies. Predictions about, for example, the potential for butyrate production based on 16S rRNA sequence frequencies will likely remain at best tentative as the actual butyrate production of the species known to be capable of doing this is highly dependent on external factors such as the diet and the presence and abundance of other bacterial species. Confirming predictions about short-chain fatty acid production profiles is furthermore likely to remain difficult as the majority of short-chain fatty acids are taken up by the colon [42] and because of the volatility of such compounds during transit and handling. In vitro co-culture experiments will, however, help to validate the importance and existence of bacterial cross-feeding complexes. In conclusion, although distinct differences have been found in each age category between the healthy and diabetic children, the main differences with regard to Clostridium clusters IV and XIVa appear to represent two sides of the same coin, as they together emphasise the importance of developing balanced bacterial cross-feeding complexes that have sufficient potential for butyrate formation.

The odds ratio for experimental versus control, stratifying for sex, is 3.42 (95% confidence interval, 1.57-7.74).