Clinical and Public Health Microbiology

NIH Workshop:
The Human Microbiome – Conference Round-Up for August 16, 2017

CONFERENCE ROUND-UP – August 16, 2017

The Human Microbiome: Emerging Themes at the Horizon of the 21st Century

Microbes inhabit just about every part of the human body, outnumbering human cells by ten to one. The ten-year, National Institutes of Health (NIH) Common Fund Human Microbiome Project was established to understand how microbial communities impact human development, physiology, immunity, brain development, and behavior, and to create research resources for this emerging field.

This 2017 NIH-wide microbiome workshop was organized by a planning committee of the trans-NIH Microbiome Working Group (TMWG)1, which includes program staff from the 19 NIH Institutes, Centers and Offices that support human microbiome research through their extramural portfolios. The TMWG is interested in taking stock of where the microbiome field stands after NIH’s ten-year investment in the Human Microbiome Project and evaluating what is needed for this field to advance over the next decade. This meeting will cover advances that reveal specific ways that microbiota influence the physiology of the host, in both health and disease, and how the microbiota may be manipulated at the community, population, organismal, or molecular level to maintain and/or improve host health.

Below are summaries of only a few of the sessions that occurred today.  To hear all the sessions, go to the NHGRI web site (https://www.genome.gov/) and access the livestream on demand recordings for each day of the conference.  Each session lasted 15 minutes to give more speakers a chance to contribute and to give attendees as large an overview of the field as possible.

 

The Impact of the Microbiome of the Female Reproductive Tract on Health and Pregnancy

(Gregory A. Buck, presenter – Virginia Commonwealth University)

The researchers focused on the influence of the cervical, vaginal, and rectal microbiomes on preterm pregnancies (< 37 weeks).  According to 2005 World Health Organization data, 12 million preterm pregnancies occur every year with a fetal mortality that can be up to 40 percent, depending on the country in which the pregnancy occurs.  Many of the infants who survive preterm pregnancies have long-term health issues.

Preterm pregnancies occur most often in people of African descent.  The reasons for this may be genetic, environmental, or a combination of both, but they have not yet been determined.  The presenter said that an epigenomic exploration of the phenomenon was high on his list of priorities.

The team took cervical, vaginal, and rectal microbiome samples at intervals during the pregnancies of 1,594 women.  At birth, samples were taken from the amniotic fluid, cord blood, placenta, and uterine membranes and from stool samples of the babies.  Altogether, analyses were performed on 231,391 samples over 3.5 years.  Most of the data from these analyses will be posted on the DCC database and will be open access.  Controlled access data will be stored in the dbGAP database but the databases will be linked so those who have access to controlled information can find it.

Conclusions so far include:

  • cytokine profiles and communal states are correlated and can predict microbiome transitions throughout pregnancy,
  • the most microbial diversity was observed during the first trimester of pregnancy and tapered off significantly during the second trimester, and
  • the vaginal microbiome during the second trimester contained unexpected complexities.

 

Integrative Personal Omics Profiling During Periods of Environmental Stress

(Michael P. Snyder, presenter – Stanford University)

The conclusions from this presentation were that the personal microbiome remains robust and individual through short-term perturbations, but is disrupted by long-term problems.  The subjects wore a variety of devices on their bodies – including monitors for heart rate, skin temperature, respiration, and insulin sensitivity – that continuously tracked metabolic signs and produced 250,000 pieces of data per day apiece.  It turned out that once the individual’s baseline parameters were established, these monitors were able to accurately pick up changes in metabolic signals that heralded incipient bacterial and viral infections.

 

Characterizing the Gut Microbial Ecosystem for Diagnosis and Therapy in Inflammatory Bowel Disease (IBD)

(Curtis Huttenhower, presenter – T.H. Chan Harvard School of Public Health and Broad Institute)

This research group first studied five cohorts of adult and pediatric Crohn’s disease and ulcerative colitis patients who provided biweekly stool samples for a year each.  The researchers received a total of 4,000 samples and have processed 2,000 of them.  Their conclusions were that the microbiomes of Crohn’s disease and ulcerative colitis are different and also vary within each category.  Patterns of disease activity and response to treatment were distinctive.  The team found that when fewer organisms were present in a microbiome, they all worked harder to sustain function.  They also discovered that IBD was caused by facultative anaerobic organisms such as ruminococcus nevis.

In their next study, the team tried to describe the “normal” human microbiome by examining microbial activity on multiple sites on the bodies of 300 healthy participants.  The team took samples from 15 sites on the men and 18 sites on the women over several visits and entered all the data into the Cloud.  They discovered “host-enriched” pathways all over the body that depended on good metabolic nutrition, such as adequate B vitamins, and site-specific microbiomes in each sample area.

The team plans to explore what the microbes they have identified actually do and how they help create the microbiomes in which they live.  They also found so much protocol variation between studies in the literature that data comparison was impossible.  They plan to develop a menu of experimental design possibilities to standardize microbial research and give it statistical integrity.

 

Ethical Issues in Human Microbiome Research: Beyond the Usual Suspects

(Mildred Cho, presenter – Stanford University)

In the early days of microbiome research, ethical considerations were focused on the moral, legal, and social issues surrounding sample collection and disseminating data, such as giving the results of analyses to research subjects and protecting privacy.

Recently there has been a rapid shift from observation and characterization to experimental research and clinical interventions, sometimes on the part of the many companies now in microbiome research and sometimes on the part of “citizen scientists.”  There are many clinical trials of practical applications of microbiome research, and sometimes research goes straight to the consumer, like the smartphone nutrition App based on your microbiome.  The probiotics industry will reach $45 billion in sales by 2018.

All this change happening at breakneck speed is eroding the boundaries of traditional scientific behavior.

Microbiome research is in a grey zone between research and medicine where the boundaries are blurred.  Ordinary people can participate, getting funding through crowdsourcing sites on the Internet, getting research participants through personal networking, and setting up datasets like Open Biome on the Web.

Categories are often non-existent, but categories are important.  If you are a doctor and you stick a knife in someone during surgery that’s OK, but if you knife someone on the street, it’s not.  We have to define people’s roles and how to regulate them.

There are non-scientists doing scientific activities, such as 23 and Me.  What obligation do citizen scientists have to produce generalizable information that can be duplicated?  They are not required to go through IRBs, undergo peer review, or share their results with anyone.

A good example is Fecal Matter Transplant (FMT).  The FDA first listed it as a biologic drug, but the initial trials were done by people working on their own and they were very effective so the FDA backed down and doesn’t regulate FMTs like it does other treatments.  Josiah Zaner put out a do-it-yourself guide: all you need is a blender, a turkey baster, and ziploc bags.  What are the ethical considerations for desperate parents who try FMT on their children with serious diseases?

The upside of citizen science is that your work may be more relevant to you and friends, you can recruit lots of people easily through crowdsourcing, and you might enable research not supported by NIH (postdocs who can’t get funding are proponents of citizen science).  The downside is that it is hard to ensure external and internal validity, there may be self-selection bias because the people who will participate in your trial were interested anyway and have the time to do it, it is hard to establish therapeutic effectiveness validity on your own, and there definitely can be conflicts of interest.  Do you know how to screen patients?  One citizen trial recruited 150 people but ended up with data on only three because everyone else lied about admission criteria and had to be eliminated, were deceptive in other ways, or broke protocol.  Can you weigh the risks and benefits accurately?

These sorts of questions create ambiguity that makes evaluating citizen research on the microbiome difficult.  Our goal should be setting up systems that make people think about ethics and do the right thing rather than creating regulations.

There were also sessions on using Drosophilia, zebrafish, and swine for microbiome research and the advantages and disadvantages of each. 

For more information, click here: https://commonfund.nih.gov/hmp/meetings/emerging

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