The microbiome affects celiac severity in mice

In non-celiac people, gluten is broken down into its constituent proteins and does not elicit any immune response.  In celiac disease, however, the gluten proteins cause inflammation, which can result in a number of GI issues.  The microbiome has long been thought to play a role in this disease, because of its importance to immune mediation, and its role in gluten breakdown.  An international group of scientists recently tested the role of various different characteristic microbiome communities on the immune reaction in mice with celiac disease.  They published their results last week in the American Journal of Pathology.

The scientists used a mouse model for celiac disease that involved genetically modified mice that had an immune response to gluten.  They split the mice into three groups, one group had a typical healthy microbiome, the next had a healthy microbiome but without proteobacteria, and the final group was germ free (i.e. completely lacking a microbiome).  When the germ free mice were challenged with gluten they had the highest inflammatory response.  This included increases in immune cells, and breakdown of the intestinal villi.  Unsurprisingly, when the germ free mice were colonized with normal microbiota, their inflammatory response was attenuated.   The scientists then discovered an important relationship between celiac’s and Proteobacteria.  The mice that harbored this phylum had more severe responses to gluten, suggesting that these bacteria somehow worsen the inflammatory response to gluten.  Antibiotic treatment that increased the amounts Proteobacteria, and the relative abundances of Escherichia, Helicobacter, Pasteurella, and Lactobacillus, also increased the inflammatory response.

The exact mechanisms by which the microbiome are mediating the immune response are unclear.  Bacteria are known to induce various immune cells and also break down gluten, and these mechanisms may be involved.  In either case gluten sensitivity and celiac disease are clearly affected by the microbiome.

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