Blog Post August 29, 2013

Outnumbered: my microbiome, my health

Our bodies are made up of a lot of individual cells.

How many is a lot? There’s no way to calculate it precisely. Early sources such as Isaac Asimov and the Encyclopedia Brittanica say 50-75 trillion cells, and biologists at Arizona State University estimate 60-90 trillion. Wiki Answers goes a bit higher with 1014 (100 trillion) but disturbingly writes it as 1,000,000,000,000,000, which last I knew was one quadrillion, providing a nice demonstration of why it’s not wise to use wiki-anything as an authoritative source.

Ironically, however, the one quadrillion figure from Wiki Answer is actually close to correct if you add one more cellular component—the number of microorganisms in and on the human body. The consensus figure is that we host 10 times as many microorganisms as we have cells in our body. Therefore, we carry with us something in the neighborhood of a quadrillion cells, regardless of exactly how many trillion are our own. 

Yes, that’s nearly 1,000,000,000,000,000 cells in addition to our own, comprising what’s known as our microbiome.

Microbiome research

It can be difficult to view the microbiome as its own entity, as necessary to our function and survival as our own organs. For one thing, most people think first about infectious pathogens and the diseases they can cause, and that has cast a negative shadow over our perception of the microbial world. And we view our own genes, 23,000 of them give or take, as far more central to our existence than the ~8 million microbial genes from the thousands of different bacterial strains that share our space. But we depend in part on the vast colonies of microbes for our health and wellbeing, and, in balance, the nuanced interplay between cells benefits all.

Many recent revelations have arisen from a surge in research looking into the microbiome’s composition, activity, interactions with the host organism (a.k.a. us) and its impact on health and disease. The Human Microbiome Project (HMP), begun in 2007 and funded by the Common Fund at the National Institutes of Health, has played a large role in bringing more attention to the microbial communities with which we coexist. HMP researchers are collecting and sequencing a reference set of microbial genome sequences, with strains collected from five sites: nasal passages, oral cavities, skin, gastrointestinal tract and urogenital tract. HMP researchers published a large amount of data in a series of reports in June 2012, which the NIH characterized as having “mapped the normal microbial make-up of healthy humans, producing numerous insights and even a few surprises.” While anyone associated with biomedical research flinches a bit at the word “normal,” it was indeed a formidable effort that lays the groundwork for starting to determine what tips the balance toward disease and other health problems.

A walking ecosystem

Not surprisingly, balance is an important concept when looking at the microbiome. As with larger ecosystems, our microbiomes generally flourish in harmony with us when provided with a stable, balanced environment. Interestingly, however, different places on our bodies host such different microbial colonies that the NIH press release about the HMP said “each body site can be inhabited by organisms as different as those in the Amazon Rainforest and the Sahara Desert.”

While our microbial partners play vital roles throughout the body, much attention has been focused on the gut microbiome. Deservedly so, as it is here that symbiosis is most evident, with microbes allowing us to properly digest food and absorb more nutrients. Each intestinal microbiome is composed of up to 1,000 species of bacteria, as well as relatively small populations of other microbes, including viruses and eukaryotes. Three bacterial groups dominate: the Firmicutes, Bacteroides and Actinobacteria, though the exact composition of the populations varies between individuals. Indeed, the relative percentages may play a significant role in weight management, as reported in recent research findings. 

Obvious perturbations to the system—the use of antibiotics, for example, or a diet consistently rich in high-fat, high-energy foods—create disruptions to the microbiome that can influence health and metabolism in animal model experiments. There are strong indications that variations in these areas can influence the human microbiome as well, though the human research inherently involves far more variability.

Fun with correlation and causation

Investigations into the microbiome have shown that our non-pathogenic microbes likely influence our health far more than previously thought. Indeed, new findings are being broadcast that make it seem like there’s little health-wise that the microbiome doesn’t influence, particularly when it comes to our digestive systems. Recent research has implicated certain populations of microorganisms in contributing to neonatal health, diabetes, mental health, behavior and even longevity in addition to weight management.

The clinical possibilities are more than a little intriguing, and the ongoing research is likely to yield powerful medical insights. Nonetheless, it makes sense to be somewhat cautious when reading about the power of the microbiome at the moment. Indeed, well-known researcher Jonathan Eisen from the UC Davis Department of Medical Microbiology has gone so far as to create an “overselling the microbiome” award. Its most recent recipient was a press office whose headline implied that its institute’s research showed that intestinal flora determined the health of obese people, rather than being correlated with health and risk status.* And as covered in this space before, getting from correlation to cause-and-effect is a difficult task. Therefore, as reports of new and tantalizing findings make their way into the media—and they will—remember the words of Dr. David Relman, a Stanford microbiologist, speaking with The New York Times after the HMP published its initial findings last summer. It was a veritable deluge of data, but, Dr. Relman said, “we are scratching at the surface now.” It is, he said, “humbling.”