Type 2 diabetes and the microbiome. iHMP blog #4

Universal symbol for diabetes

Nearly 10% of individuals in the United States suffer from type 2 diabetes, and the associated costs are hundreds of billions of dollars.  Several studies have correlated microbiome alterations with the presence of diabetes, and studies in mice have shown that changes in the microbiome can lower glucose levels, putting the mice at risk for diabetes.  The iHMP plans on studying diabetes and its associations with the microbiome through a longitudinal study. 

Specifically the iHMP will be testing the following hypotheses:
1) "Environmental stress causes dynamic changes in specific biological pathways in the human body, and these changes lead to alteration of the human microbiome...including glucose."
2) "Some of the changes may affect the [hosts' gene regulation] leading to...biological alteraions that extend well beyond the time of the stress period"
3) "Different physiological stresses, such as respiratory viral infections and diet changes, may have common effects in both the host and microbiome"
Source

The iHMP will investigate these hypotheses by enrolling a cohort of 60 adults at risk for diabetes.  The study will last 3 years and during these years the researchers expect at least 10 individuals to become diabetic.  They will sample the patients' stool, nasal, urine, skin, tongue, and blood microbiomes every 2-3 months, which will measure a full suite of biologics that include bacteria, lipid content, metabolites, and proteins.  Sampling will also occur during periods of 'stress' that include mental stress as well as illnesses and physical trauma.

As always the results of the study will be made available, and we will be checking in on their progress.

This blog post concludes our series on the iHMP (HMP2).  We hope that anyone reading this will continue to check in on the iHMP progress, as we hope the role of the microbiome in pregnancy, IBD, and diabetes continues to unfold. 

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.

Vaginal microbiome during pregnancy. iHMP blog #2

Gardnerella Vaginalis, a bacteria associated with spontaneous preterm labor.

The vaginal microbiome undergoes many changes during pregnancy, and it has been associated with various afflictions, such as gestational diabetes, low birth weight, necrotizing enterocolitis, and colic.  In addition, infection of the uterine cavity is correlated with preterm labor, especially for early preterm labor.  For now though, the crucial role of the microbiome during pregnancy remains largely unknown.

The iHMP will define the  healthy pregnancy microbiome, and investigate how deviations from the healthy microbiome may contribute to preterm birth and still birth.  The iHMP will do a longitudinal study (study spanning the length of the pregnancy and some time after) of 2,000 women, some of whom will be at risk for preterm birth.  The women will have their entire microbiomes, not just vaginal microbiomes, examined regularly during the course of pregnancy and thereafter.  Other microbiome samples include the placenta, amniotic fluid, umbilical cord, and the child's microbiome as well.  This study will measure bacteria, lipids, cytokines, and proteins, which have all been associated with pregnancy disorders.  The cohort will consist of women who are racially diverse and have a wide range of ages.

One of the motivations for this project was a study published in the New England Journal of Medicine in 2000 that reviewed intrauterine infection and its link to preterm birth.  Preterm birth is most often caused by spontaneous labor or rupture of membranes, and is highly correlated with infection.  For more information, follow the link above.

The human microbiome project, part 2. iHMP blog #1

The human microbiome project (HMP) was a large scale program sponsored by the NIH's common fund, which sought to define the healthy human microbiome.  The HMP was a success, and its main findings serve as a foundation upon which most microbiome science is built (cited almost 700 times in 2 years!). Perhaps it was the unexpected successor to the human genome project (HGP), but it is already nearing the HGP in influence.  

Because of its success the NIH is sponsoring the human microbiome project 2 (HMP2), otherwise known as the integrative human microbiome project (iHMP).  Where HMP1 investigated what the human microbiome looked like, iHMP is looking at how the human microbiome is associated with various "exemplars of microbiome-associated human conditions".  

These three conditions are:

1) "Pregnancy, including those that end in preterm birth"
2) "Gut disease onset, using inflammatory bowel disease (IBD) as a model"
3) "Respiratory viral infection and onset of type 2 diabetes (T2D)"

iHMP will track large cohorts of individuals for each of these conditions for 3 years to perform complete longitudinal studies.  Many variables and data sets will be tracked, compiled, and made public.  Of course bacteria will be sampled, but, for the first time, comprehensive sampling of metabolites from those bacteria will also be performed. The results of iHMP will be published periodically and will last from 2013 to 2016.

We would like to thank the entire HMP consortium of scientific investigators for their efforts, but especially Lita Proctor, who has championed the microbiome within the NIH for many years.  Her perspective on iHMP, which was recently published in Cell, was the basis for this blog post and from where the quotations are drawn.

We will will kick off a 3 part blog series here on the AMI blog where I review the 3 microbiome conditions that are being studied in the iHMP.  Check back on Monday for a post discussion about how the microbiome is associated with pregnancy, and how the iHMP plans to perform its investigation.