The human microbiome: there is still a lot to do

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

Before that, microbiologists knew that the body harbored a large mass of microorganisms – a heady mix of bacteria, as well as archaea, fungi and viruses, spread over the skin, in the mouth and in the gut – together dubbed the microbiome. But until 2012, we lacked an inventory.

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 486, 207–214; 2012), and revisits the project to represent humanity in all its complexity.

It took a long time to begin this first work, and the pace of change over the past ten years has been staggering. It wasn’t until high-throughput gene sequencing technologies – originally developed to study the human genome – became cheap and easy enough to use that HMP could begin.

After its launch in 2007, the consortium sequenced the DNA of microbes found in and on 242 people from 2 American cities – Boston, Massachusetts and Houston, Texas, chosen for their proximity to the two main sequencing centers of the time, 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 Common Fund, and the project employed academic microbiome bioinformaticians to work on the data after it was generated.

The result was the first comprehensive catalog of a healthy human microbiome in the United States: a comprehensive list of gut microbe genes. The HMP showed that the cellular organisms of the intestine consist of thousands of species, with a genetic fingerprint 150 times larger than the human genome. Eventually, this abundance led biologists to view the microbiome as a “second genome” acquired from the environment, hidden within the human host.

Ten years later, we know much more. The microbiome is essential for the proper functioning of our body, key to digesting food and warding off 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 influences microbiome development – ​​is also becoming clearer.

(Given how fundamental microbes are to our health, I still find it amazing that we outsource so many functions to a myriad of organisms that we pick up from our environment, right from birth.)

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

This first scan a decade ago, recruiting people from just two US cities, failed miserably 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 the differences between groups of humans.

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

Finding out more will require a new consortium, sampling thousands of people and animals. We need wildlife biologists and microbiome scientists working side by side, with teams around the world. Ten years ago, analysis was so new and difficult that we hardly spared the acquisition of samples. Now, acquiring samples from sources around the world should drive the process.

Some might ask why we need a new, large and expensive consortium when data is already trickling in – one study at a time, by labs working alone. But industrialization is moving fast, and modern economic forces have the power to wipe out microbial diversity faster than can be observed.

A new consortium would allow scientists to finally complete the map of the microbiome. It’s like a human census: you don’t wait for individual cities to report their population; you make one concerted effort to do it consistently and quickly, before that changes.

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

Competing interests

The author declares no competing interests.

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