A recent study of humans with celiac disease who were treated with helminths raised the possibility that an increase in microbial species richness (i.e. the number of different species present) could regulate gluten-induced inflammation in the gut.
In general, studies indicate that a rich and diverse microbiota is a healthy one. But is richness the only thing that matters when it comes to the microbiota’s effects on the immune system in celiac disease?
One clue comes from a recently published paper by Elena Verdú, Associate Professor at McMaster University (Canada) and GMFH board member. Her group showed that gut microbiota can positively or negatively affect immune reactions involved in celiac disease. In the study, mice who were genetically susceptible to a celiac-like disease were tested under 3 microbiota conditions: no gut microbiota, eight strains of benign bacteria, and a normal, complex microbiota that included pathobionts. After inducing gluten sensitivity, the team found that both germ-free mice and those with a complex microbiota had increased immune reactions to gluten, while mice colonized with benign bacteria had reduced reactions to gluten.
In this model, microbial richness was not what mattered most. Verdú says, “What we saw was that the mice that had the conventional microbiota, which is the more complex — compared to the benign microbiota, of course, it’s richer and more diverse — those responded to gluten with a pro-inflammatory effect.”
She explains, “The ones with the limited bacteria, with the eight strains, those were the ones that were protected… [and] when we further expanded the pathobionts [in the conventional mice, they] got even worse.” The presence of pathobionts increased microbiota richness, then, but also indicated the potential for negative effects on the immune system in this mouse model of celiac disease.
“I don’t think it’s that simple: a matter of richness or diversity,” says Verdú. Even in cases of increased microbiota richness, she says, “the potential is there for a problem to arise if you have those pathobionts and you don’t have the counterbalance of the benign bacteria.”
Still, it remains possible that microbiota richness could be a generally protective factor in human celiac disease, helping maintain homeostasis in the gut. “I [may] have some of those pathobionts [associated with inflammation, but] if I have a balanced microbiota — very rich — I may not develop anything,” Verdú says.
Galipeau HJ, et al. (2015) Intestinal Microbiota Modulates Gluten-Induced Immunopathology in Humanized Mice. American Journal of Pathology DOI: http://dx.doi.org/10.1016/j.ajpath.2015.07.018
Giacomin P, et al. (2015) Experimental hookworm infection and escalating gluten challenges are associated with increased microbial richness in celiac subjects.Scientific Reports doi:10.1038/srep13797