Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study

Abstract

BackgroundA recent study using a rat model found significant differences at the time of diabetes onset in the bacterial communities responsible for type 1 diabetes modulation. We hypothesized that type 1 diabetes in humans could also be linked to a specific gut microbiota. Our aim was to quantify and evaluate the difference in the composition of gut microbiota between children with type 1 diabetes and healthy children and to determine the possible relationship of the gut microbiota of children with type 1 diabetes with the glycemic level.MethodsA case-control study was carried out with 16 children with type 1 diabetes and 16 healthy children. The fecal bacteria composition was investigated by polymerase chain reaction-denaturing gradient gel electrophoresis and real-time quantitative polymerase chain reaction.ResultsThe mean similarity index was 47.39% for the healthy children and 37.56% for the children with diabetes, whereas the intergroup similarity index was 26.69%. In the children with diabetes, the bacterial number of Actinobacteria and Firmicutes, and the Firmicutes to Bacteroidetes ratio were all significantly decreased, with the quantity of Bacteroidetes significantly increased with respect to healthy children. At the genus level, we found a significant increase in the number of Clostridium, Bacteroides and Veillonella and a significant decrease in the number of Lactobacillus, Bifidobacterium, Blautia coccoides/Eubacterium rectale group and Prevotella in the children with diabetes. We also found that the number of Bifidobacterium and Lactobacillus, and the Firmicutes to Bacteroidetes ratio correlated negatively and significantly with the plasma glucose level while the quantity of Clostridium correlated positively and significantly with the plasma glucose level in the diabetes group.ConclusionsThis is the first study showing that type 1 diabetes is associated with compositional changes in gut microbiota. The significant differences in the number of Bifidobacterium, Lactobacillus and Clostridium and in the Firmicutes to Bacteroidetes ratio observed between the two groups could be related to the glycemic level in the group with diabetes. Moreover, the quantity of bacteria essential to maintain gut integrity was significantly lower in the children with diabetes than the healthy children. These findings could be useful for developing strategies to control the development of type 1 diabetes by modifying the gut microbiota.

Streptozotocin-induced type-1-diabetes disease onset in Sprague–Dawley rats is associated with an altered intestinal microbiota composition and decreased diversity

“…The data revealed that STZ-induced T1D increased the Bacteroidetes : Firmicutes ratio, as previously demonstrated in various T1D models (de Goffau et al, 2013;Giongo et al, 2011;Murri et al, 2013). Initially, pre-T1D induction, no differences in the Bacteroidetes : Firmicutes ratio was observed between the groups.…”

“…Previous studies have examined the role of the intestinal microbiota in the development of T1D but these are often limited due to the models used [i.e. genetically pre-disposed animals (Roesch et al, 2009) and humans (Brown et al, 2011;de Goffau et al, 2013;Giongo et al, 2011;Murri et al, 2013) who develop T1D, with conflicting results. Oral administration of the probiotic compound VSL # 3 to non-obese diabetic mice prevented spontaneous T1D development (Calcinaro et al, 2005), while antibiotics have also been shown to prevent autoimmune diabetes in bio-breeding diabetesprone rats (Brugman et al, 2006).…”

“…Indeed, the intestinal microbiota is an environmental factor that cannot be overlooked as a contributor towards T1D development or a factor that is significantly altered as a result of T1D development. Many studies have linked alterations in the intestinal microbiota composition with conditions such as obesity (Ley et al, , 2005Murphy et al, 2010;Turnbaugh et al, 2006), inflammatory bowel disease (Greenblum et al, 2012), colitis (Bellavia et al, 2013;Klimesova et al, 2013) and T1D Murri et al, 2013;Roesch et al, 2009). Moreover, risk of T1D onset in childhood is higher in children delivered by Caesarean section (Cardwell et al, 2008), where there is also altered microbiota composition (Dominguez-Bello et al, 2010).…”

The gut microbiota and inflammatory noncommunicable diseases: Associations and potentials for gut microbiota therapies

“…Increased gut permeability and intestinal inflammation with impaired immune-regulatory mechanisms have been shown in children with allergic disease 55 , and also in children with type 1 diabetes 56 . Consistent with reports of dysbiosis in children with allergic manifestations, an aberrant gut microbiome has been associated with type 1 diabetes 57,58 . 16S-sequencing revealed differences in the gut microbiome in children with signs of ß-cell autoimmunity compared to healthy children of the same age and sex, with similar feeding history and genetic risk 57 .…”

Integrated multi-omics of the human gut microbiome in a case study of familial type 1 diabetes

“…Gastrointestinal agents have been implicated in this process due to the immune-modulatory role of the gastrointestinal tract 26,27 and the potential involvement of the pancreatic ducts in the inflammation that culminates in beta-cell destruction 28 . Case-control studies of the microbial community structure during [29][30][31][32] , immediately after 33,34 and before 31,35 seroconversion, have tried but failed to identify generalizable disease-causing or biomarker organism signatures. The present study does not focus on the aetiology, but examines a relatively small cohort of individuals living with T1DM to determine whether there are effects that are apparent in the structure and function of the gastrointestinal microbiome linked to T1DM.…”