Research Initiatives Around the Microbiome


What does a “healthy” microbiome look like? Who is part of a microbiome? How can we quantify and analyze our microbiome?

The Human Microbiome Project (HMP), a $173 million project by the NIH, was initiated to address these questions. It focuses on a comprehensive characterization of the human microbiome and the development of computational tools for the analysis of microbiome data. In 2012, NIH announced the first referenced data of a normal bacterial makeup in healthy individuals. Tissue samples from different body sites of 242 people were collected and sequenced to understand the structure and diversity of the healthy human microbiome. Scientists found that the microbiome contains 360 times more microbial genes than human genes that are involved in vital metabolic functions like digestion or the production of anti-inflammatories. Read the original article published in Nature to find out more.

The American Gut project follows another approach. Rather than carefully selecting test subjects, the founders wanted to involve the national and international public. So far, several thousand people have followed their call. If interested, you can still join the American Gut project!

Earlier this month, American Gut published preliminary results for more than 3,000 participants which described microbial composition and factors that affected the gut habitat, such as age and diet.

Individual Findings- Lone Fighters

Large studies are not necessary to contribute to the understanding of our microflora. Larry Smarr gathered information from blood and stool samples that showed early signs of the disease process, years before the first detectable symptoms of his late onset Crohn’s disease.

In another self experiment, Jeff Leach, founder of the Human Food Project and collaborator of American Gut, studies the effects of various dietary patterns on his gut microbiota.

And lots of unanswered questions

The research on the human microbiome is just getting started. Although important steps have been made towards defining the human microbiome and its role in diseases, many questions remain to be answered. Are associations with health and disease causal? How can this newly generated knowledge contribute to the development of interventions? In which diseases does the microbiome play a causal role?

Group Findings

A few years earlier, in 2012, an NIH press release announced the definition of a normal bacterial makeup in healthy individuals. This provides a much needed reference in order to study the role of the microbiome in diseases. This research article by Bäckhed et al.  elaborates on how understanding the properties of healthy microbiota could contribute to the development of interventions. The results of HMP have implications for other research fields such as epidemiology, as described by Foxman and Rosenthal.

Although science has provided important insights into the role of the microbiome in some diseases, it is still unclear whether these relationships are causal. 

Next time you look at a fellow human, pretend to be Neo from The Matrix, only try to see the trillion cells and around 23,000 genes that make up his or her body. Then, take a second look and try to imagine that the microbes within his or her body outnumber the human cells by a factor of 10.

Stay with us to find out in the next post, how scientists deal with this vast amount of information that would blow even Neo’s mind.

What questions would you like to learn more about next?


The Human Microbiome: An Invisible Spouse in Sickness and in Health


The second we are born, each of us enters a unique relationship that is going to last a lifetime. Who’s the lucky one, you ask? About 100 trillion microbes that dwell everywhere on and inside our body: the skin, the mouth, the gut. Click on the individual words in this Scientific American interactive map to explore who lives within us.

Your enemies are my enemies: The Economist describes the symbiotic relationship between us and our microbes; while we offer them shelter and raw materials, they provide nutritional services and synthesis of vitamins, as well as protection from interlopers. They also educate our immune system to discriminate between thousands of harmless species and pathogens.

Unfortunately, as in most marriages, times are not always as harmonious as we would like them to be. Disbalances in our microbiome have a striking effect on the body and have been associated with a wide variety of diseases: metabolic conditions, such as type 2 diabetes and obesity; heart disease;  asthma and eczema; and even autoimmune disorders like inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and rheumatoid arthritis.

A New York Times article explores the complexity of the human microbiome and efforts to restore order to the microbial system.

The human microbiome is unique in every person and varies from day to day. Eric Alm from MIT tracked his gut microbiome for a whole year and noticed that no day is the same in the microbial universe (see his  2012 GET Conference talk). He did so by collecting and measuring stool samples every single day. Read another New York Times article to find out about new surveys that help scientists measure and understand the microbiome.

This slideshow by David A. Relman (Stanford University) views our invisible spouse as a complex ecosystem and addresses important characteristics: diversity, stability, and resilience.

Watch this video by NPR to get an overview of the functions of the microbiome. 

In our next few posts, we will be learning more about how we interact with our microbiome.  What specific topics would you like to learn about?

The Celiac Disease Foundation: Raising Awareness and Promoting Research

Elaine Monarch suffered from a mysterious illness for most of her adult life.  It was only in her 50s that she received an accurate diagnosis: celiac disease (CD).  CD is an autoimmune disease that causes damage to the small intestine when a person eats gluten, a protein found in common grains like wheat.  Ten years ago, the medical community thought that CD was a rare disorder that affected only 1 in every 10,000 people: primarily children who had digestive problems and failure to thrive.  Now, it is thought that celiac disease currently affects at least 1 in 100 people worldwide (a four-fold rise in prevalence from the 1950s).  Despite the rising incidence, only 1 in 6 people with the disease gets correctly diagnosed.  

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Elaine knew that she wasn’t the only one who’d faced the challenges of undiagnosed CD.  Even armed with her diagnosis, she couldn’t find a physician who took her seriously: the disease was not yet widely acknowledged as real.  These frustrations led her to start the Celiac Disease Foundation (CDF), in 1990.

Since then, CDF has made substantial progress in raising awareness among the general public, the medical community, and the food industry.  

  • CDF organized a march on the FDA, CDC, and NIH, in order to win recognition of celiac disease as a legitimate illness in need of funding and research.  After fighting for ten years, CDF succeeded in pressuring the FDA to create rules for gluten-free labels on food.

  • A gluten-free diet used to mean forgoing common staples like bread, and driving long distances to over-pay at speciality and health food stores.  The CDF worked with large food companies such as General Mills and Frito-Lay to initiate gluten-free versions of their popular items.  

CDF is also heavily invested in education for both patients and doctors on both celiac disease and non-celiac gluten sensitivity.  Their website offers an informational quiz used by 10,000 people each month.  If a person’s symptoms resemble celiac disease, the website can help find a local practitioner who can conduct a formal screening and diagnosis, which may include blood work and an endoscopy.

Since many physicians and the general public remain unaware of celiac disease and non-celiac gluten sensitivity, CDF conducts physician grand rounds, sends speakers to conferences and delivers outreach to the public with a simple message: “Consider Celiac, Request The Test.”  

To complement their educational work, CDF emphasizes advocacy and has a strong voice in influencing policy.  They hope that an upcoming 2015 policy summit will lead to a nationwide platform for screening and diagnosis of CD in America.  Marilyn Geller, CEO of the CDF, describes the crucial importance of diagnosis:

“A lot of physicians will hear patients describe celiac-like symptoms and tell them to go gluten free without giving a referral for a diagnosis.  That’s a problem, since celiac disease is such a gateway disorder for other autoimmune problems.  If you don’t have a firm  diagnosis and the medical required need for the gluten-free diet, it’s too easy to cheat  and do lasting damage to your digestive system.  And with no diagnosis, there’s no follow-up. Nobody is checking to see how you’re doing on your diet, testing for your vitamin levels, bone density - all those things that need to happen.  The gluten free diet is not the panacea for everything that affects a person.”

As Marilyn mentioned, there is growing evidence that celiac disease does increase the likelihood of developing other autoimmune disorders.  The CDF is working to promote awareness of celiac disease and non-celiac gluten sensitivity to help people get diagnosed and bring their disease under control.  I wonder whether their efforts will help to slow the rising tide of autoimmunity as a whole.

For further information consult the following sources:

More details about the gluten-free diet, written by physicians:

Multiple Myeloma Research Foundation: One Person’s Power to Ignite Collaboration

Kathy Giusti was an ambitious Harvard Business School graduate with a promising career in the pharmaceutical industry.  Her attention was focused on her work, her growing family, and their new home, but the trajectory of her life took a dramatic turn when she was diagnosed with Multiple Myeloma, a rare blood cancer, at the age of 37.  At that time, in the mid-90s, there was so little understanding of Multiple Myeloma that Kathy’s diagnosis was the equivalent of a death sentence; she wondered whether her one-year-old daughter would even remember that she’d had a mom.

Seeking the best treatment she could find, Kathy was shocked to learn that the state of the art in 1996 was the same as it had been in 1956, when her grandfather had battled the disease - a testament to the lack of awareness, lack of funding, and ultimately lack of any progress in fighting this disease.  Kathy felt frustrated and turned her personal charisma and business acumen toward solving this problem.  She founded the Multiple Myeloma Research Foundation to raise funds and attract talent to help combat the disease.  

Kathy took a measured approach.  She first identified the main reasons for the lack of progress: the rarity of MM meant that pharma companies had no monetary incentives to make the substantial investment needed to develop treatments.  In the rare cases where research was happening, scientists jealously guarded their data and results.  Kathy knew she had to attract funding and convince scientists who had been competitors to become collaborators.   

Generous donations from organizations and peers who believed that Kathy could make a difference allowed MMRF to expand from a grant-writing role to a full-fledged foundation.  Kathy set to work creating collaborative models to bring disparate researchers together:

The Multiple Myeloma Research Consortium brings together top academic centers to conduct clinical trials, enrolling patients 10% faster than the industry average - a testament to the MMRC’s high level of efficiency.  These trials have already given over 1,000 patients access to lifesaving treatments.

The MMRC’s biorepository is the largest, best, and first of its kind.  Its 4000+ annotated GLP-quality bone marrow and blood samples allow researchers to conduct previously-impossible genomics studies.

The Multiple Myeloma Genomics Initiative is a leader in genome mapping.  It has already mapped the full genomes of over 200 MM patients.  Further, the results of this research were made widely available to hundreds of researchers worldwide via a public portal - a pioneering step in open collaboration.  

The MMRF is also leading the charge toward personalized medicine with the CoMMpass study, which aims to recruit 1000 patients and learn how their unique genetic profiles impact the progression of their illness and their response to treatments.  This project represents a significant partnership between academia and industry.

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The MMRF’s innovative approach to disease research has attracted praise and investment, and contributed to unprecedented progress in improving the MM prognosis.  Kathy and her organization have been recognized by Harvard, Time Magazine, and Forbes.  The foundation has attracted $250 million in donations to date, which has been used to fund 500 researchers and bring 6 FDA-approved drugs to market.  As a result of new drugs and treatments, the average life expectancy for those diagnosed with MM has more than doubled, from 3 years to 8 years.  

The impact that the MMRF and Kathy have made on the lives of those with MM is enormous.  What’s even more tremendous is the potential for catalyzing progress in other diseases by applying a similar business model.  Anne Quinn Young, VP of Development and Strategic Partnerships at the MMRF, described what sets this organization apart from others: “Our donors tend to be entrepreneurs who appreciate our business-oriented approach to nonprofit work - we’re willing to take risks but always backed by a sound business plan.”  

How can we work together to apply a similar model to help connect stakeholders in autoimmune disease and lead to faster treatment and cures?  All ideas welcome!

The Rare Genomics Institute: Fostering Collaboration by Breaking Down Barriers between Patients, Resources, and Researchers

Jimmy Lin, MD PhD MHS, thinks of his digital health nonprofit startup, The Rare Genomics Institute, as an “Amazon-slash-Kickstarter for Science.”  Jimmy was inspired to start the RGI when he met a family whose young son had a rare disease.  The family was exhausting their resources going from doctor to doctor, failing to find anyone who could help their child; not one organization was conducting research on his particular disease.  Jimmy was aware of advanced genomic techniques from his background in cancer, and he was aware of the deplorable lack of progress in fighting rare disease.  As he and his friends - all veterans of top medical institutes - founded RGI, they wanted to figure out how to “leverage the technologies that have been so helpful in cancer, in order to help kids diagnosed with rare diseases.”

Jimmy knew that genomic sequencing could help in rare diseases, but one major barrier to sequencing is the high cost: $7 - 10 thousand.  Since paying such a price out-of-pocket is not feasible for most families, RGI incorporated an innovative crowdfunding platform.  Families create a profile to describe their child’s struggle and solicit donations from friends, families, and even strangers.  Once the funding goal is reached, RGI’s volunteer scientists conduct a full DNA sequence and identify genes with unusual changes that might be responsible for a patient’s symptoms.  The goal is to develop a diagnosis, conduct research on the mutations using living organisms such as worms, and ultimately deliver a tailor-made treatment to the patient.  

RGI is a pioneer in the field of truly personalized, individualized medicine.  As Jimmy says, “rare disease is the perfect place to start out with personalized medicine. By definition, with rare disease, there are no large numbers, so it has to be personalized.”  RGI’s approach is also extremely patient-focused.  By putting patients in control of their own data, the pace of innovation can be increased, says Jimmy: “[patients] have the greatest stake, and they can say, ‘it’s my data; I’ll give it to anybody who wants it.” 

This is just one way that the RGI benefits science as a whole - not just individual families.  Ultimately, the organization serves to create a landscape of increased connectedness among all rare disease stakeholders, most of whom were previously acting alone.  Patients get unprecedented access to cutting-edge tools that used to be the preserve of the wealthy.  The scientific community is introduced to questions that are so rare they might never have otherwise been asked.  Jimmy hopes that the RGI’s collaborative network can help overcome the siloing that has slowed research in rare diseases and in medicine generally.  He has ambitious plans for the organization’s future: “In a year I would like to be able to officially launch our platform’s ultimate goal: to help anybody with any disease do any research.”  

Personally, I’m hopeful that such a model could also break down barriers and speed up progress in the siloed world of autoimmune disease.  Are you?

Smart Patients: Harnessing the Exponential Power of Patient Microexperts

Roni Zeiger MD is a physician who thinks that doctors have a lot to learn from their patients.  As the former Chief Health Strategist at Google, Roni spent a great deal of time thinking about how people search for medical information online.  He began to notice that “it’s easy to find a lot of decent quality info online if you’re looking for something common or general.  But once you get to a specific context or situation, or a rare disease, then most of what you find online is really superficial.”  

Further, says Roni, we shouldn’t assume that doctors necessarily have all the answers.  He notes that when patients are diagnosed with a disease, they and their loved ones can quickly become more knowledgeable than their doctors with regard to their own particular situations.  When Roni looked at online medical message boards, he discovered high-caliber, scientifically informed discussions.  However, all of this expertise was not accessible to web searches, meaning that it was not benefiting as many people as it could.

The existence of this untapped treasure trove is what motivated Roni to partner with Gilles Frydman to start Smart Patients, an easy-to-use community platform focused on oncology and health.  This site allows patients and caregivers to connect and learn from one another’s experience and knowledge in a question-and-answer format.  Roni remarks that complicated health situations are unique - each person’s exact combination of conditions, symptoms, and life circumstances is unprecedented in medical history.  Therefore, the best advice often comes from a network of microexperts - a group of people, each of whom has deep knowledge of one aspect of a certain condition.  When people on Smart Patients ask tough questions, they benefit from a multitude of opinions and perspectives, including those from different disease backgrounds, as is evident in the screenshot below.


Smart Patients earns the trust of users by implementing sophisticated safeguards for privacy and users’ data.  None of the site’s content is publicly accessible, and the site is monitored to ensure that only patients and caregivers - not researchers or industry representatives - can make accounts.  Further, the site promotes a culture of respect, so the communities are self-monitoring against misinformation or rude remarks.

Roni believes that the healthcare system is failing to incorporate user-centered design. Smart Patients has begun to work with academics and researchers, generating insights from relevant communities to improve the design of clinical trials.  Roni hopes that this will lead to clinical trials that are more user-friendly and accessible.  

Smart Patients aims to challenge the top-down paradigm of traditional medicine, helping professionals learn from patients’ stories and experiences to improve healthcare as a whole.  As an indication of Smart Patients’ early success, representatives of other diseases have asked to incorporate the Smart Patients platform into their own patient communities.  

I can see ways that the autoimmune community could benefit from using this platform.  What do you think?


Thank You - BRC D2D Keynote Address





Thank you to all those who contributed to my research for my recent keynote address at BRC D2D. 

Zephyr Health: Variety and Visualization Creates Useful Information

The dimensions of Big Data can be summed up by The Four Vs: Volume, Variety, Velocity, and Veracity.   

But however large or diverse one’s data, it can often be hard to find exactly what one needs.

As a researcher, I spend a lot of time on Google. I might open a multitude of tabs just to find a few good answers. I wish I had a multilayered document where I could click and drill down to find new information efficiently as new questions arise during the research process.

William King, founder and CEO of Zephyr Health, experienced a similar problem while working at Johnson & Johnson, so he set out to build “a product that would bring together information quickly and in a way that customers can visualize.”

Zephyr Health is a business solution targeted to decision makers in healthcare, allowing business users to connect multiple sources of data from both private and public datasets and turn them into organized, actionable information. Each of the applications in Zephyr’s suite provides several layers of information and different ways to extract and analyze data. With the click of a button you can view multiple levels of detail - the perfect research tool!Zephyr picture 2

As shown below, if you want more detailed information about a practitioner, a hospital, or a clinical trial, it is all available on the same screen in an intuitive, easy-to-use interface.

Once you select the category of information, you can easily view details on a practitioner, such as how many clinical trials he has done, how much NIH funding he has received, or how many publications he’s produced. This allows pharmaceutical companies to easily identify the best candidates for clinical trials.image

“As a big data analytics company, the great thing about our applications is that they draw disparate data sources together and then use algorithms to solve a specific business problem,” continued William King.

Zephyr Health’s data analytics platform optimizes efficiency and accuracy in the clinical trial site selection process as well as in patient recruitment and post-approval marketing. The goal is to deliver beneficial drugs to the patients that need them faster than was possible before, ultimately improving or even saving lives.

Overall, I am excited because Zephyr Health’s easy-to-use approach provides an elegant way to take large, disparate data sets and turn them into useful information. I can envision many of the healthcare stakeholders finding this approach useful – medical device manufacturers, hospitals, researchers who work with large datasets, and more.    

As a healthcare consumer who also happens to be a visual learner, I would love to see this easy-to-understand approach applied to my medical records and lab results. What do you think?