July 4, 2022

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There is still a lot to do

There is still a lot to do

This week marks the 10th anniversary of the first major survey of microbial diversity in the human body, published in temper nature by the Human Microbiome Project (HMP) consortium, of which I was a member.

Before that, microbiologists knew the body hosted a large mass of microorganisms — an intoxicating mixture of bacteria, along with archaea, fungi and viruses, spread over the skin, mouth, and intestines — together dubbed the microbiome. But until 2012, we lacked an inventory of them.

In fact, this inventory – an indicator of 10 trillion cells belonging to thousands of species, weighing a total of 200 grams per person – is still incomplete. It is time to build on this early work (Human Microbiome Project Consortium temper nature 486, 207-214; 2012), and the renewal of the project to represent humanity in all its complexities.

It has taken such a long time to get this early on, and the pace of change over the past 10 years has been staggering. Only once high-throughput genetic sequencing technologies — first developed to examine the human genome — are cheap and easy enough to use, can HMP start.

After its launch in 2007, the consortium sequenced the DNA of microbes found in and on 242 people from two American cities – Boston, Massachusetts, and Houston, Texas, selected for their proximity to the two prominent sequencing centers at the time, MIT and Harvard University near Boston, and the College of Baylor Medicine in Houston. Our activities were funded by the US National Institutes of Health Joint Fund, and the project attracted academic bioinformatics experts for the microbiome to work on the data after we generated it.

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The result was the first comprehensive catalog of an intact American human microbiome: a complete list of genes present in the gut microbiome. HMP showed that cellular organisms in the gut consist of thousands of species, with a genetic footprint 150 times the size of the human genome. Ultimately, this abundance led biologists to view the microbiome as an ecologically acquired “second genome,” hidden in the human host.

Ten years later, we know a lot. The microbiome is essential to the proper functioning of our bodies, and is key to digesting food and fending off pathogens. Experiments in mice have shown that the composition of the microbiome affects levels of social engagement and anxiety. Common diseases such as cardiovascular disease and obesity are associated with distinct microbiomes. How children acquire their microbiomes — and what influences microbiome development — is also becoming more clear.

(Given how important microbes are to our health, I still find it surprising that we undertake so many functions for many of the organisms we pick up from our environment, right from birth.)

We also have a lot of unanswered academic questions. Where did the microbiome first come from in human evolution? How do human microbes differ from those of primates, mammals, or animals in general? How is the microbiome transmitted from one person to another? And what do changing sterile diets and lifestyles mean for the long-term health of the microbiome?

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

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And even less is known about many other animals which themselves contain masses. We know that the microbes of captive animals differ from those of animals living in the wild, in the same ways that industrial human microbes differ from non-industrial ones. But most of what we know about animal microbes comes from studies of captive animals. As we lose animal diversity due to rapid global change, we are also losing microbiome diversity.

Learning more will require a new consortium, sampling thousands of people and animals. We need wildlife biologists and microbiome scientists working side by side, with crews all over the world. Ten years ago, the analysis was so new and difficult that we didn’t think much about getting the samples. Now, getting samples from global sources should drive the process.

Some may wonder why we need a massive and expensive new consortium while the data is already pouring in — one study at a time, conducted by labs working on their own. But industrialization is moving fast, and modern economic forces have the potential to eradicate microbial diversity faster than can be observed.

A new consortium would enable scientists to finally fill in the map of the microbiome. It’s like a human census: Don’t wait for individual towns to report their population numbers; You make one concerted effort to do it consistently and quickly before it changes.

An extensive new analysis of the diversity of the human microbiome, and of the broader vertebrate microbiome, will finally put our species data in the context of the tree of life. Only then can we really expand the label “human” to the microbiome.

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conflict of interest

The author declares no conflict of interest.