The presence of a commensal intestinal microbiota in infancy is critical for numerous physiologic processes including growth, angiogenesis, optimization of nutrition, and stimulation of various arms of the innate and adaptive immune systems (1
). With this, it is surprising that the effects of intestinal microbiota on the development of type 1 diabetes remain an area subject to somewhat limited investigation.
What does seem clear is that rodent models of type 1 diabetes, including NOD mice and related substrains, are more likely to develop disease under specific pathogen-free conditions (5
). Furthermore, diabetes-prone BB rats (BBDP) subject to Cesarean derivation have been noted to develop accelerated disease (7
). In terms of using such information to proactively modulate diabetes formation, the provision of antibiotics, such as fucidic acid, Colistin, and Bactrim, in BB rats after weaning (8
) lead to diabetes prevention, whereas in our own efforts using the NOD mouse, a decreased frequency of type 1 diabetes was observed with the administration of doxycycline (10
). The specific mechanisms of how such therapies modulate disease are unclear, but it is clear that changes in the microbiota affect the development of autoimmune diabetes in both animal models. Supporting this view, oral probiotic administration to NOD mice was noted to induce interleukin (IL)-10 (i.e., an anti-inflammatory cytokine) production and prevented the development of type 1 diabetes (11
Interest exists on intestinal microbiota composition, a metric that has previously relied almost exclusively on the quantitative cultures from feces. At this time, we are not aware of any published studies that have demonstrated differences in intestinal microbiota of animals or humans with or at high-risk for the development of type 1 diabetes. Furthermore, most microbial species in the intestinal microbiota are not amenable to culture. With the knowledge that environment influences the development of type 1 diabetes and that the gastrointestinal tract provides the greatest surface area for interaction of the environment, this is an area that begs further investigation.
Over 500 species of microbes are known to reside in the human gastrointestinal tract (1
). Their interaction with the mucosal immune system, especially in the first years of life, may have life-long effects. As but one example, differences in the composition of intestinal microflora between healthy and allergic infants in countries with a high and low prevalence of allergies have been noted and precede clinical symptoms (12
). Furthermore, probiotics have been successfully used as immunomodulators in the prevention and treatment of allergies in children (13
), findings indicating that commensal bacteria are not innocent bystanders in humans but active players in the shaping of the immunological network of the host. Hence, new approaches for evaluating the interactions between the intestinal microbiota and barrier and innate immunity are needed.
Among the most promising molecular techniques that have recently been developed to fill this void are those that enable detection of uncultivatable species and that are amenable to statistical microecologic analyses. Some of these methods target 16Ss RNA gene sequences, as they contain signatures of phylogenetic groups and sometimes even species (15
). Other techniques apply PCR with denaturing or temperature gradient gel electrophoresis, fluorescent in situ hybridization and shotgun sequencing DNA (16
), and whole metagenomic approaches (17
). These techniques offer promise for future efforts seeking to establish a causal link between the intestinal microbiota and type 1 diabetes, as well as to the identification of aberrant microbiota that could be targeted for disease prevention strategies.