We are vastly, ridiculously, hopelessly, humblingly outnumbered: For every one human cell, there are an estimated 10 single-cell microbes in us or on us, at least 100 trillion in all, nestled in our guts and in our urogenital tracts, lying on our skin and happily ensconced in our mouths and noses--entire civilizations of fungi and protozoa and (mostly) bacteria that eat and breathe, evolve and reproduce and die.
Before you reach in horror for the hand sanitizer or industrial-strength mouthwash, you might want to keep something in mind. A profusion of research in just the past five years is showing that our microbial hitchhikers, collectively called the "human microbiota" and so small they account for only 1 or 2 percent of our weight, play a key role in maintaining our health. And we disrupt them at our peril. "It's not possible to understand human health and disease without exploring the massive community of microorganisms we carry around with us," says Professor George Weinstock of Washington University in St. Louis. Knowing which microbes live in healthy people "allows us to better investigate what goes awry in diseases that are thought to have a microbial link, like Crohn's and obesity."
The microbes in our body--especially some of the 10,000 or so species of bacteria in and on us--have indeed been implicated in disorders as diverse as obesity and Crohn's, and also in asthma, heart disease, sinusitis, and possibly even mood disorders. They influence how big our appetite is and, possibly, even what foods we crave. They synthesize vitamins and affect how quickly we metabolize drugs such as acetaminophen (Tylenol), they protect against esophageal reflux and they churn out many of the same neurochemicals as our own brains. Given this job description, it's hardly surprising that when perturbed, scientists are discovering, the microbiota can tip us into poor health or outright illness.
Exactly how our bacterial companions affect our health is the subject of ongoing research in labs around the world, but one thing is clear: Our decades-long war on germs is looking seriously wrongheaded. In an effort to obliterate disease-causing microbes through antibiotics and anti-microbials--from the pills we down for a cold (against which antibiotics are useless) to the meat we eat to the hand-sanitizer-dispensers everywhere you look--we are carpet-bombing our microbiota. And that war on germs takes a huge toll on beneficial bugs, too.
One example: The bacterium Helicobacter pylori causes ulcers and has been linked to stomach cancers. Although it was once in almost everyone's gut, it is now found in just 6 percent of U.S. children, Science magazine reported in 2011, probably due to the widespread use of antibiotics and anti-microbials. That should mean fewer ulcers, but there's a dark lining to that silver cloud: H. pylori may ward off asthma. Scientists led by Dr. Martin Blaser of New York University Langone Medical Center found that those without H. pylori are more likely to have had childhood asthma than those with it. Coincidence? In 2011 scientists in Switzerland infected half of a colony of mice with the bacteria and left the other half germ-free. They showered all the mice with dust mites and other allergens. Mice with H. pylori were fine; those without suffered airway inflammation, the hallmark of asthma.
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Exactly how H. pylori might ward off asthma is still a mystery, but researchers have made progress understanding the link between our microbiota and other diseases.
The field of microbiota and health took off in 2006, when scientists led by Jeffrey Gordon of Washington University in St. Louis noticed something: Fat mice and svelte mice have very different gut microbes. Could different microbes actually cause obesity? To find out, Gordon transferred gut bacteria called Firmicutes from obese mice into thin ones. The thin mice ate no more than they used to, but they quickly started packing on the pounds (okay, ounces). Firmicutes, it turns out, are really good at liberating calories from food, much better than the common gut bugs called Bacteroidetes. That finding offers a hint of why your friend can scarf down calories and remain slim while you have merely to walk past a bakery window to gain weight. "Some microbes change how efficiently we metabolize food," says biologist Rob Knight of the University of Colorado, who studies the genetics of the microbiota, called the microbiome.
It seems Firmicutes are quite adept at digesting fats and carbs, allowing you to absorb many more of, say, the 1,200 calories in half of a Domino's bacon-cheeseburger pizza than if you have fewer Firmicutes and more Bacteroidetes. "Obesity depends not just on calories ingested but also on the microbiome," says Dr. Yang-Xin Fu of the University of Chicago Medicine. And, yes, like mice, obese people tend to have more Firmicutes and fewer Bacteroidetes than slim people.
At this point everyone asks, how can I get my slim friend's menagerie of gut microbes? Short answer: Scientists don't know yet. But they have some clues. For instance, Bacteroidetes--the microbes linked to slimness--proliferate in the presence of fructans, a form of fructose found in asparagus, artichokes, garlic, and onions, among other foods, notes microbiologist Andrew Gewirtz of Georgia State University. A diet high in fructans might support a good crop of slimming Bacteroidetes. On the other hand, he notes, stress decreases the abundance of Bacteroidetes, suggesting one more way stress causes obesity.
"Lots of people are exploring the possibility of using antibiotics or prebiotics or probiotics to treat obesity," says Colorado's Knight. Prebiotics are foods that promote the growth of some bacteria at the expense of others. Probiotics are live microorganisms such as the Lactobacillus in yogurt; the idea is to ingest beneficial ones. The strategy with antibiotics would be similar: Zap the obesity-promoting ones. These ideas are in their very earliest stages, so don't go looking on your drugstore shelves for such products just yet.
Much clearer is the strong evidence that modern medicine's penchant for antibiotics has a downside beyond the well-known problem of breeding antibiotic-resistant bugs. A study of 11,532 children found that, on average, those exposed to antibiotics for the usual childhood ills, such as ear infections, from birth to 5 months of age weighed more for their height than other kids. By 38 months, they had a 22 percent greater likelihood of being overweight, scientists reported last August. "The rise of obesity around the world is coincident with widespread antibiotic use," says Blaser. "It is possible that early exposure to antibiotics primes children for obesity later in life." That's one reason farmers add antibiotics to animal feed: The drugs alter the gut bacteria in cattle, pigs, and others, substituting bacteria that are better at extracting maximum calories from feed and thereby making the animals pack on the pounds.
Before exploring how else the microbiota influence our health, it's worth taking a step back to cover some of the basics. It starts with birth. The bacteria and other microbes you enter the world with come from your mother's skin (if you were a Cesarean baby) or birth canal. "At first, all your biota resemble your mother's," says Knight. "We don't really know how fast the microbiota of the skin or gut or nose change, but within two or three years they're like an adult's," having picked up microbes from the air, water, clothing, and diet. This last part is vital: What we eat shapes what microbes our guts harbor. In 2010, a study found that Japanese people harbor gut bacteria that digest nori, the seaweed used in sushi. Westerners don't. Why? The Japanese consume lots of fish, which contain marine bacteria, which digest nori. "What you eat," says microbiologist Justin Sonnenburg of Stanford University School of Medicine, is "one of the major determinants" of your gut microbiota.
It isn't just obesity. The list of illnesses linked to the population of microbes in your body seems to get longer every month, but here's a quick tour.
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- Tooth decay. A single species of bacteria is the chief cause of most cavities: It turns the sugar we eat into acid that eats away tooth enamel. Scientists are working on a mouthwash that would kill this bacteria, raising hope that tooth decay will become a thing of the past.
- Chronic sinusitis. Last September, scientists led by Susan Lynch of the University of California, San Francisco, reported that the nasal microbiota of chronic rhinosinusitis (CRS) patients had low levels of good-for-you bacteria and abnormally high levels of a not-so-good bacteria. When the scientists depleted the microbiota of mice to make them like CRS patients', sure enough, the animals developed sinusitis. And transplanting that bug into mice inhibited the growth of sinusitis-causing bacteria and prevented infection.
- Excessive appetite. Certain gut bacteria produce a compound called PYY, which makes you feel full and reduces how much you eat. Absent those bacteria, your brain doesn't get the "stop eating" signal. And H. pylori (of ulcer-causing fame) regulates the stomach's production of ghrelin, an appetite-stimulating hormone. Several labs have found that people whose stomachs harbor more H. pylori have less ghrelin and thus less hunger; conversely, fewer H. pylori means more ghrelin and greater likelihood of overeating.
- Autoimmune diseases. The microbes in your gut play a role in regulating the immune system and therefore autoimmune diseases such as rheumatoid arthritis and Crohn's, researchers at the Mayo Clinic and elsewhere have found. For instance, one powerful gut bacterium has anti-inflammatory properties, protecting against recurrence of Crohn's disease. More generally, the immune system seems to consider some gut microbes dangerous invaders, unleashing an attack that produces the inflammation characteristic of arthritis and Crohn's.
- Atherosclerosis. Patients with this disease characterized by hardening of the arteries had different types of gut bacteria than healthy people, scientists reported in Nature Communications last December. In particular, the gut bacteria of those with atherosclerosis had fewer genes for the production of natural antioxidants linked to heart health; patients therefore had less of these antioxidants in their blood.
In December 2007 the National Institutes of Health launched the Human Microbiome Project to study the role the microbiome--the genes in our microbiota--plays in health and disease. Based on samples from 242 healthy people, 18 to 40, Project scientists announced in 2012, the microbiome consists of some 8 million functional genes from about 10,000 individual species--or 360 times as many genes as the 22,000 or so in our own DNA. "It's like a second genome," said Colorado's Knight, one of the Project scientists.
Where all this leaves someone who wants to cultivate healthy microbiota is only starting to become clear. One obstacle is that "nobody knows what an ideal or even normal human microbiome is," says Jeff Leach, an anthropologist. To help find out, in 2012 he launched "American Gut." A crowdsourced research project, it invites anyone to request a sample-collecting kit ($99), basically a super-long Q-tip that you use to swab used toilet paper and send back for analysis. A questionnaire asks about some of your general habits and lifestyle: what pets you have, whether you have taken antibiotics recently, what you ate over the past few days, and other behaviors thought to affect the gut microbiota. In return, you get back the list of your gut microbes and how you cluster or compare to other people.
That's only the start. Until scientists can give us the recipe for healthy microbiota, experts say it pays to heed the advice of mainstream medical groups, which recommend restricting the use of antibiotics to only must-have circumstances, not every cough and sniffle. Consider buying antibiotic-free meat. "The scorched earth outcome of many broad-spectrum antibiotics is analogous to spraying poison all over your backyard plants and grass, and waiting to see what grows back," says Leach. In both cases "invasive and maybe not-so-good species" can move in, with harmful results.
Be wary of manufacturers making exaggerated claims about probiotics and prebiotics. While some claims are supported by research [see "Post Investigates: Probiotics," Jul/Aug 2012], others "greatly outstrip the scientific evidence," says Knight. But just because commerce has galloped ahead of science doesn't mean there is no scientific basis for manipulating the microbiome to improve health. "We can't change our first genome, the one we inherit from our parents," says Colorado's Knight. "But we can change the second, the microbiome. And that holds real promise."
