Immune cells are educated in the gut to not attack beneficial bacteria

The gastrointestinal tract is made up of trillions of bacteria that are largely ignored by the body’s immune system.  Why is it that the body’s immune system knows to ignore these beneficial bacteria that are so important for our ability to live a healthy life? The answer to this question could play an important role in understanding how to maintain a healthy gut and how to treat diseases. Scientists led by Gregory Sonnenberg at Weill Cornell Medical College may have answered this question in a study published last week in Science.

The researchers studied T cells, cells that are made in the thymus and are trained there to kill-off foreign microbes and other intruders that make their way into the human body. But why don’t these T cells attack helpful bacteria in the GI tract? They found that the T cells are again educated in the gut to not attack beneficial bacteria but when this education is disrupted, it can lead to disease.  For example, inflammatory bowel diseases like Crohn’s disease and ulcerative colitis occur when the immune system attacks the GI tract and bacteria in the GI tract.

In the thymus, T cells that could attack the body are destroyed before they are released into circulation. In the gut, a type of cell called innate lymphoid cells (ILCs) educate the T cells to not attack beneficial bacteria. These ILCs had previously been found to make a physical barrier between the bacteria in the gut and the immune system.

In mice, they found that ILCs attacked T cells that were destroying beneficial bacteria and when they prevented this attack by ILCs on the T cells, severe intestinal inflammation resulted. They also looked at intestinal biopsies of young patients with Crohn’s disease. In the biopsies they found that the ILCs lacked specific molecules that are important for educating the T cells not to attack the bacteria in the gut. They found that a decrease in this molecule correlated with an increase in pro-inflammatory cells in children with Crohn’s disease.

The authors state that it may be possible to get rid of these T cells that are causing the inflammation and by doing so you may be able to help treat the disease.  By restoring this molecule (Major Histocompatibility Complex class II) that is preventing the education of the T cells, pro-inflammatory T cells may be reduced resulting in reduced intestinal inflammation.

A gluten free diet and IBD

The University of North Carolina recently published the results of a study based on a longitudinal internet survey conducted by the Crohn's and Colitis Foundation of America (CCFA).  Almost 1700 people with inflammatory bowel disease (IBD) participated in the study including many people with Celiac disease, others who were gluten-sensitive, and even more who had tried a gluten free diet.  In the study, 66% of participants who were on a gluten free diet had improved gastro-intestinal symptoms, and 38% reported improvement of IBD flares. This study shows that potential role that diet, especially a gluten free diet, may have in IBD management.

However this study was only based on a longitudinal internet survey, and not as rigorous as clinical trials.  We must also keep this in mind in light of a recent study that suggested a gluten free diet placebo effect, though these studies were hardly robust and had their problems as well. 

While this post is not necessarily focused on the microbiome, there have been clear associations between Celiacs, IBD, nutrition, and the microbiome.

Inflammatory bowel disease (IBD) and the microbiome. iHMP blog #3

Micrograph of inflammation of the large intestine with IBD

Inflammatory bowel disease (IBD) encompasses a group of diseases that include Crohn's disease and ulcerative colitis, among others.  Thus far, IBD has proven to be a very complex disease, with no straight-forward microbial causes.  Instead, it has been linked to the overall health of the microbiome, which includes disproportionate populations of healthy and unhealthy associated bacteria and their metabolites.

The iHMP is tackling the connection between IBD and the microbiome through a longitudinal IBD study.  The study will recruit 90 patients who are: adults recently diagnosed with IBD, children recently diagnosed with IBD, people with established cases of IBD, and people with no IBD who will serve as controls.  Each person in the study will sample his/her own stool once every 2 weeks for 1 year. The stool will be sampled for its entire microbial community, including bacteria and viruses, as well as proteins, and metabolites.  In addition, biopsies will be performed on the patients' guts periodically over the year.  Finally, blood samples will also be taken.

The overall goal of the study is threefold:
1) "identifying the molecular mechanisms by which the intestinal microbiome may trigger...IBD"
2) "determining if microbial composition predicts subsequent risk of flareups in [IBD]"
3) "testing whether successful response to therapy can be predicted from the stool microbiota"
(source)

This study will be completed within the year and all the data will be made available at ibdmdb.org.  Check back with this blog throughout the year for updates.

I also want to draw attention to the great work being supported by the Crohn's and Colitis Foundation of America's (CCFA) microbiome initiative.  The CCFA is entering the later stages of their own research projects and I encourage any interested people to check out the CCFA website.