The human microbiome: there is still a lot to do

The human microbiome: there is still a lot to do

This week marks the tenth anniversary of the first major study of microbial diversity in the human body, published in Nature of the Human Microbiome Project (HMP) Consortium, of which I was a member.

Before that, microbiologists knew that the body hosted a large number of microorganisms – an intoxicating mixture of bacteria, along with archaea, fungi and viruses, spread over the skin, in the mouth and in the intestine – collectively called the microbiome. But until 2012, we lacked an inventory of them.

In fact, this inventory – an index of 10 trillion cells belonging to thousands of species, weighing a total of 200 grams in each person – is still incomplete. It is time to build on this early work (Human Microbiome Project Consortium Nature 486207-214; 2012), and renew the project to represent humanity in all its complexity.

It took a long time to start the early work, and the pace of change over the last ten years has been fantastic. Only when high throughput gene sequencing technologies – first developed to examine the human genome – became inexpensive and easy to use could HMP begin.

Following its launch in 2007, the consortium sequenced DNA from microbes found in and on 242 individuals from 2 U.S. cities – Boston, Massachusetts and Houston, Texas, selected for its proximity to the then two prominent sequencing centers, the Broad Institute of MIT and Harvard near Boston, and Baylor College of Medicine in Houston. Our activities were funded by the US National Institutes of Health’s joint fund, and the project involved academic bioinformatics in microbiome to work with data after we generated it.

The result was the first comprehensive catalog of a healthy American human microbiome: a complete list of genes in the gut microbes. HMP showed that the intestinal cellular organisms consist of thousands of species, with a genetic footprint that is 150 times as large as the human genome. Eventually, this abundance led biologists to view the microbiome as an environmentally acquired “second genome,” hidden in human values.

Ten years later, we know much more. The microbiome is crucial for our bodies to function properly, the key to digesting food and repelling pathogens. Experiments on mice have shown that microbiome compositions affect levels of social engagement and anxiety. Common diseases such as cardiovascular disease and obesity are linked to distinct microbiomes. How babies acquire their microbiomes – and what affects the development of microbiomes – is also becoming increasingly clear.

(Given how basic microbes are to our health, I still find it amazing that we put so many functions on countless organisms that we retrieve from our environment, from birth.)

We also have many unanswered academic questions. Where did the microbiome first come from in human evolution? How do human microbiomes differ from other primates, mammals or animals more generally? How do microbiomes move from person to person? And what do changing diets and lifestyle changes mean for the long-term health of the microbiome?

The first analysis ten years ago, which recruited people from just two American cities, failed to capture the true diversity of the human microbiome. We now know that people living in Europe and North America have less diverse microbiomes than people living in less industrialized regions – but too little is known about differences between groups of people.

And even less is known about the amount of other animals that themselves contain amounts. We know that microbiomes in captive animals differ from those in wild animals, in much the same way that industrialized human microbiomes differ from non-industrialized ones. But most of what we know about animal microbes comes from studies of animals in captivity. When we lose animal diversity due to rapid global change, we also lose microbiome diversity.

Learning more will require a new consortium taking samples of thousands of people and animals. We need wild biologists and microbiome researchers working side by side, with herds around the world. Ten years ago, the analysis was so new and difficult that we did not save much on taking samples. Now, provincial collection from sources globally should lead the process.

Some may ask why we need a new, grand, expensive consortium when data is already seeping in – one study at a time, conducted by laboratories working alone. But industrialization is rapid and modern economic forces have the power to wipe out microbial diversity faster than can be observed.

A new consortium would give researchers the opportunity to finally fill in the microbiome map. It’s like a census: you do not wait for individual cities to report their population figures; you make a single concerted effort to do it consistently and quickly, before it changes.

A comprehensive new diversity analysis of the human microbiome, and of the broader vertebrate microbiome, will finally place our own species’ data in the context of the tree of life. Only then can we really extend the label “human” to the microbiome.

Competing interests

The author does not declare competing interests.

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