Cool Microflora Translational Study with Celiac Disease

There has been a deluge of articles regarding the microbiome; yet, many aspects of microbiome derangements may have limited clinical significance.  In addition, in many circumstances, it is not clear if the changes in the microbiome represent the proverbial chicken or the egg.  How much of the changes in the microbiome are a consequence rather than a cause of a clinical problem?

One fascinating article (A Caminero et al. Gastroenterol 2016; 151: 670-83) looks at the role of the microflora with regard to gluten breakdown and immunogenicity.  Thanks to Ben Gold who prompted me to take a 2nd look at this study.

In this study, the authors took bacteria isolated from the small intestines of Celiac disease (CD) patients or controls and colonized germ-free mice.  Subsequently, “after gluten gavage, gliadin amount and proteolytic activities were measured” and characterized.

Key findings:

  • Pseudomonas aeruginosa isolated from CD patients “produced peptides that better translocated the mouse intestinal barrier.”
  • The P aeruginosa-modified gluten peptides activated gluten-specific T-cells from CD patients.
  • In contrast, Lactobacillus spp isolated from the duodenum of non-CD controls degraded gluten peptides and reduced their immunogenicity.

The others selected P aeruginosa from CD patients as it was not present in controls, though most strains were in fact within the phylum Firmicutes.  Lactobacillus spp was chosen from the healthy subjects “because it constitutes a core resident group in the human small intestine that is involved in gluten metabolism in vitro and is altered in CD patients.”

  • Figure 2 specifies the distinct gluten metabolic patterns induced by the intestinal bacteria.
  • Figure 3-6 show numerous changes in the immunogenicity of gluten peptides induced the intestinal bacteria.

Overall, the study provides some evidence that changes in microbiome could trigger intestinal inflammation.  Thus, since autoimmunity and celiac disease have an environmental trigger, this study implicates changes in the microflora as a risk factor for developing celiac disease in the susceptible host (see Figure 7 in the source article).

My take (from authors): This study identified “both pathogenic and protective microbe-gluten-host interactions that may modulate autoimmune risk in HLA-DQ2 susceptible persons.”

Acadia Natl Park

Acadia Natl Park

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