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.

Human microbiome market poised for economic growth

A recent economic forecast was published which projects the growth of the microbiome market to be $650 million by 2023.  The report states that the major drivers in the microbiome will be therapeutics and diagnostics.  It also anticipates diseases such as obesity, diabetes, cancer, and mental disorders will possibly be treated with microbiome therapeutics by that time through the use of prebiotics, probiotics, food, and drugs.  The projection shows that growth will be driven in Europe, followed by Asia, and then the United States, where the microbiome is still a "niche market due to the lack of awareness among the population regarding the beneficial usage of prebiotics and probiotics."   As for what is holding the market back: "Lack of comprehensive research..., lack of awareness among the population..., and impending government regulations on prebiotics and probiotics."

This forecast is very exciting for all those involved in the microbiome field.  Though, in order for the microbiome to reach its full potential, we must work together to remove the barriers currently restraining the field.  At the AMI we have pinpointed these same problems, and that is why the AMI's mission is to "improve health through microbiome research, education, and advocacy."  We fund and support research efforts that create and prove the efficacy of microbiome therapeutics.  We educate the public to raise the profile of the microbiome field.  We advocate for the microbiome to government entities not only to raise awareness about current microbiome science, but to encourage preparedness for its maturation.

At the AMI we are convinced the microbiome is the next frontier of human health, and we are well positioned to accelerate the growth of this nascent field. 

Caesarean sections, breast feeding, and the microbiome

There is a growing amount of literature on the subject of babies' microbiomes because it is clear that the first few years of life are crucial to the development of the immune system, and poor development can have lasting, life-long consequences.  As we have learned, a healthy microbiome is absolutely critical to a healthy immune system.  Evidence for this connection is vast, but starkly manifests itself in germ-free mice which can not survive long due to autoimmune disease.  So, as the thinking goes, a healthier microbiome as a baby leads to a healthier life.

In any case, a commentary was recently written by AMI Scientific Advisory Board members Maria Gloria Dominguez-Bello, Rob Knight, and a colleague that discusses how delivery mode and infant feeding affect babies' microbiomes.  As it turns out, epidemiological studies on large human populations have correlated Caesarean Section (C-section) delivery to obesity, asthma, celiac disease and type 1 diabetes, which are all autoimmune diseases.  Breast feeding, on the other hand, leads to decreased risk for some of these same diseases.

Research has shown that both C-section and breast feeding have a direct and significant influence on an infant's microbiome.  During vaginal delivery the child's gut is inoculated with the vaginal microbiome, whereas in a C-section the child's gut is associated more with the skin microbiome.  In addtion, breast feeding contains prebiotics that encourage certain bacteria to grow, which selects for a specific infant gut microbiome.  

Interestingly, the authors mention a study that showed the microbiota from the breast milk may actually be different depending on the mode of delivery.  They also comment on a study that showed certain gut bacteria are found in the vaginal microbiomes of pregnant women, as if prepared to inoculate the child.  This is in agreement with another study from Jacques Ravel which I have already blogged about.

It is very important to consider the microbiome when a woman is giving birth and feeding.  If a C-section is required it may be possible to inoculate the child's gut manually, and studies are currently investigating this.  The results of these studies will be the topic of a future blog. 

Antibiotics, obesity, and the microbiome

A paper published last month in Cell by AMI Scientific Advisory Board member Marty Blaser at NYU investigated the role and conseqeunces of low dose antibiotics early in life in mice.  Blaser and his team took two groups of infantile mice, and exposed one group with low doses of penicillin and left the other group alone.  The mice that were given the low doses of antibiotics ended up becoming overweight later in life compared to the group that was not given antibiotics.  Then, the team took the microbiome of each group and transplanted it into germ-free infantile mice that were given no antbiotics.  The germ-free mice that were given the microbiome of the lean mice were lean later in life, while the germ free mice that were given the microbiome of the obese mice were obese later in life.  In addition, when both groups of mice were given high fat diets, the group with low dose antibiotics gained more weight.

Interestingly, the antibiotic group of mice still had an abundance of highly diverse bacteria, however these mice were lacking certain strains that were found in the normal mice, and thus may be critical to later health.  The team discovered rather unambiguously that the obesity was induced by the microbiome.  The mechanism for how this occurs is still unknown, but the researchers suggested changes to normal metabolic processes and the immune system that could occur.  Overall this study shows the importance of a healthy microbiome early in life and the dangers of antibiotics early in life, because they both can have lasting consequences into adulthood.

Obesity and the microbiome

An article was published late last year by Jeff Gordon which studied the impact of human's microbiome in mice.  In the paper the researchers studied pairs of human twins who were discordant in obesity, meaning one of the twins was obese and the other was not.  Each twin's microbiome was transplanted into a germ-free mouse.

The results showed that the obese twin's microbiome made the mouse obese, whereas the lean twin's microbiome made the mouse lean.  Then, the two mice were put together and fed a low fat diet.  This caused the lean mouse's microbiome to establish itself in the obese mouse, which prevented further weight gain.  When the mice were put together and fed a high fat diet, the lean mouse microbiome no longer was taken up by the obese mouse, and the lean mouse stayed lean while the obese mouse continued to gain weight.  

There are a myriad of studies on the microbiome and obesity, so look for more blog posts about this subject moving forward.