Eight ways microbes keep you healthy

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Eight ways microbes keep you healthy
Colorful illustration of countless and diverse microbes coalescing to form the figure of the human body
A mosaic of the diverse and pervasive microbiomes of the human body. Illustration:

They digest our food, adjust our immune system, protect our skin from infection, and play a role in obesity and severe digestive woes. They, of course, are the trillions of microbes -- bacteria, viruses and fungi -- that live in more or less peaceful coexistence with the human body.

The major microbiome is in the large intestine, where microbes aid digestion, create vitamins and deter harmful microbes. Skin and noses are other hotspots of microbial variety.

Even those who were raised to loathe bacteria probably know by now: Our cells are outnumbered 100 to one by the much smaller bacteria. We'd be dead meat without our beneficial bacteria, if only because they crowd out harmful bacteria.

Maybe that's why "Forbes named the microbiome as one of 29 trends to watch in 2015.

So let's get acquainted with some modern marvels of the microbiome:

 Photo of a chubby brown mouse holding and nibbling on a donut-ringed snack.
Could antibiotics alter the “good” microbes in our gut that keep us healthy? Obese and diabetes-prone lab mice suggest “yes.”
Photo of mouse courtesy Shutterstock.

Getting fatter

Here's one clue to the obesity epidemic sweeping the United States: early treatment with the antibiotic penicillin made mice fat. Not only that, but the mice whose mothers got the antibiotic during pregnancy were more obese than the mice that started getting the drug at weaning. Although the antibiotic did not eradicate all bacteria from the gastrointestinal (GI) tract, it did wipe out four groups of bacteria.

The fat, drug-treated mice showed liver abnormalities and an impaired response to insulin. These are two signs of metabolic syndrome, which predisposes to cardiovascular disease and type 2 diabetes.

A high-fat diet made a bad situation worse by causing greater obesity. And a further test blamed the obesity on the altered bacterial community, not the drug treatment itself.

Immune system as bug farmer?

The immune system makes a living by killing pathogens. Now we hear, in studies of inflammatory bowel disease (IBD), that it may also play a role in culturing health-giving microbes.

Immune attacks on the gut in ulcerative colitis and Crohn's disease, the most common IBDs, cause weight loss, loss of appetite and bleeding in the gut and rectum.

A recent study found that lack of the immune protein MyD88 destabilized the proportion of gut bacteria, and made the mice more susceptible to an illness resembling IBD.

"Our work highlights that the immune system shapes the composition of bacterial communities in the intestine,” says senior author June Round, assistant professor of pathology at the University of Utah School of Medicine. “This interaction is important because it’s becoming more and more clear that resident microbes are very important for our health.”

Immune system promotes a healthy bacterial community in colon

Figure showing the effect of T Cell activity on gut microbes where antibodies in the 'active' phase attach to pathogenic bacteria and block them from penetrating the gut lining.
Left: When the molecule MyD88 is active, IgA antibodies bind multiple species of bacteria in the gut, controlling the number and type of “good” bacteria. Right: When the immune system is disrupted and MyD88 is inactive, IgA binding wanes, and an imbalanced bacterial community jeopardizes digestive health.
Modified from original by Charisse Peterson

Bacteria as farmers

Just like a four-year-old, bacteria can be picky eaters. Some metabolize sugar, others fat, or some specific blend of nutrients. Now we hear that hungry gut bacteria can force the human (who is supposedly running the show) to eat what they want, when they want.

It's not clear how microbes place their order, but they may release signaling molecules into the gut that trigger activity in the immune, endocrine and nervous systems. “Microbes have the capacity to manipulate behavior and mood through altering the neural signals in the vagus nerve, changing taste receptors, producing toxins to make us feel bad, and releasing chemical rewards to make us feel good,” said study author Athena Aktipis, who is now at Arizona State University.

Artist representation of the spherical norovirus capsid
X-ray crystallographic structure of a norovirus capsid, or outer container. Norovirus is notorious for causing outbreaks of GI disease on cruise ships, but a recent study suggests that it offers benefits to the intestines in some cases.

If you are starting to wonder who's in charge around here, study co-author Carlo Maley, of the University of California at San Francisco, stressed that this is a two-way street: Our diet affects our microbiome, and changes in what we shove down the hatch can alter the species composition within 24 hours.

A good word for virus?

After all the focus on bacteria in the gut, we're finally starting to hear about viruses. One recent study tested whether a virus could restore immunity and health among mice born without bacteria in the gastrointestinal tract. These mice lacked B- and T-cells, critical parts of the immune system. Two weeks after an injection of rodent norovirus, their intestinal tissue and immunity had improved.

According to senior investigator Ken Cadwell at New York University, “Our research offers compelling data about the mutually supportive relationship between viruses and bacteria in the mouse gut and lays the groundwork for further research on precisely how the virome supports the immune system, which likely applies to humans, as well."

Grainy black-and-white micrograph of several bacteria-attacking viruses surrounding a bacteria cell and injecting their genetic information.
Graham Beards/Wikipedia The small objects tethered to the bacterial cell are bacteriophages -- viruses that infect bacteria. Scientists have associated an increase in viral diversity in the gut, especially among bacteriophages, with inflammatory bowel disease, suggesting that viruses play a role in these illnesses.
Image:Andrea Azcarate, UNC School of Medicine

“We have known for a long time that people get infected all the time with viruses and bacteria, and they don’t get sick,” says Cadwell. “Now we have scientific evidence that not every viral infection is bad, but may actually be beneficial to health, just as we know that many bacterial infections are good for maintaining health.”

A bad word for virus?

Viruses are not all benign, however. In a study at Washington University in St. Louis, human IBD patients had greater viral diversity than healthy controls. Much of the increased viral diversity appeared in viruses that infect bacteria, called bacteriophages.

Study author Herbert Virgin IV, professor of pathology, speculated that changes in the gut that eliminate bacteria in inflammatory bowel diseases may unleash bacteriophages as the bacteria die. Or the introduction of a new bacteriophage to the gut, perhaps through food, may trigger a damaging reaction in the digestive system or the microbiome.

Virgin says his work adds complexity to the search to heal a condition that affects about 1 million Americans: "We know that mutations in human genes affect the risk of inflammatory bowel diseases, and scientists also are exploring how bacterial genes may influence risk.” Referring to the totality of viral genes present in the body, he added, “Our results show that the virome’s potential effects on the gut also need to be a part of these investigations.”

Photograph of a frothy bee and a hardy bread loaf.
Toast the biota! Some gut microbes have a rare and specialized mechanism for breaking down tough yeast carbohydrates present in beer, wine and bread, all produced with critical help from our favorite industrial microbe.
Photo: davecurlee

This beast eats yeast

Do beneficial gut bacteria consume traces of yeast from beer, bread, soy sauce and wine? Yeast cell walls contain a tough carbohydrate called mannan, and researchers have now revealed the metabolic machinery that Bacteroides thetaiotomicron uses to break down mannan.

That machinery seems to be rare, and so eating yeast could support a healthier gut, according to this early finding. “One of the big surprises in this study was that B. thetaiotaomicron is so specifically tuned to recognize the complex carbohydrates present in yeasts,” says Eric Martens, in the University of Michigan department of microbiology and immunology. “Even the relatively small amounts of yeast that we commonly consume in foods are enough to impact the physiology of our friendly gut bacteria.”

The researchers suggest that a better understanding of how the bacteria eat yeast could lead to better prebiotics for treating bowel diseases. Prebiotics are compounds that enhance the activity of probiotics like lactobacillus in yogurt.

Beating allergies

 Photo of a farmer holding a bunch of peanut plants pulled directly from the earth.
Peanut allergies affect three of every 500 people in the US, according to the National Institutes of Health, but microbial communities may help reduce allergic reactions.

Food allergies have risen about 50 percent in the United States between 1997 and 2011. Is there a role for the microbiome? In 2014, researchers led by Cathryn Nagler, of the University of Chicago, evoked a strong allergy to peanuts in mice devoid of bacteria.

When the germ-free mice got a dose of Clostridia bacteria, that allergy receded. However, dosing the animals with Bacteroides, a different beneficial gut bacteria, had no effect.

The investigators credited the protection to interleukin-22, an immune signaling molecule that makes the intestine less porous. When IL-22 was present, peanut allergens could not leak through the intestine and reach the blood. But when the researchers neutralized IL-22, the leakage and the peanut allergy symptoms recurred.

“We’ve identified a bacterial population that protects against food allergen sensitization,” Nagler said. “The first step in getting sensitized to a food allergen is for it to get into your blood and be presented to your immune system. The presence of these bacteria regulates that process.” She cautions, however, that the relationship requires further study.

Finding drugs

Photo of a well-prepared bowl of yogurt adorned with fresh pecans
Several beneficial bacteria in the genus Lactobacillus inhabit the mouth, intestinal tract and vaginal tract, and help the body break down dairy products. Yogurt, shown here, is a major source of probiotic bacteria.

The gut microbiome is a zone of constant rivalry, where the signals and weapons are entirely chemical. This rivalry in the soil has produced some of the best antibiotics, based on chemicals produced by fungi combatting bacteria. About one-third of human medicines have origins in plants, animals or microbes, and yet the human microbiome has barely been explored for drugs.

Michael Fischbach, an assistant professor of bioengineering at the University of California at San Francisco, is looking for candidate drugs in the human microbiome.

Fischbach identified more than 3,000 active clusters of genes, zeroed in on Lactobacillus gasseri, a common vaginal bacterium, and extracted lactocillin. In tests, the compound killed several species of pathogenic bacteria often found in the vagina, while sparing harmless bacteria.

The structure of lactocillin is similar to several candidate drugs under investigation at drug companies, Fischbach notes.

“We used to think that drugs were developed by drug companies, approved by the FDA, and prescribed by physicians, but we now think there are many drugs of equal potency and specificity being produced by the human microbiota,” Fischbach said.

– David J. Tenenbaum

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Kevin Barrett, project assistant; Terry Devitt, editor; S.V. Medaris, designer/illustrator; David J. Tenenbaum, feature writer


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