The Essential Book of Fermentation (9 page)

For example, take the case of
Bacteroides fragilis,
which prevents and can cure inflammatory bowel diseases in animals, including humans. It does this by making a polysaccharide coating that it applies to the intestinal wall, and this coating prevents pathogens from getting a toehold to do their dirty work. How nice. Does
B. fragilis
love its human hosts so much that it plays doctor in the gut? Well, it turns out that it has an ulterior motive. The polysaccharide coating calms the host’s immune system. Without it, the immune system would read the presence of
B. fragilis
as an infection and throw the bums out. So to keep itself healthy and happy in the human microbiome, it has learned to protect itself by protecting us. It also turns out that
B. fragilis
has been around for 500 million years, so as the human body developed through its entire evolutionary process,
B. fragilis
accompanied it, learning to do what it needed to survive in the pleasant climes of the human gut.

Does this mean that our microscopic friends actually manipulate us for their own ends? Yes, it does. Scientists in Sweden and Singapore, working together, found that mice raised in a sterile environment (without gut bacteria) were more likely to take risks than mice with normal gut flora. Normal mice tend to skulk along walls and avoid bright areas, but the sterile mice showed more willingness to walk freely in the center of their room and in brighter light. So somehow the presence of gut bacteria in mice leads them to be more wary, which increases their chance of survival, and by extension, the chance of survival of the gut bacteria that call the mouse home.

When very young sterile mice were given gut bacteria, their behavior reverted to normal skulking. But when adult sterile mice were given intestinal flora, their behavior didn’t change, leading the scientists to theorize that these behavioral changes are locked into the brain at an early age. But mouse studies are one thing, and aren’t always true for humans. Still, Sven Pettersson, a prominent Swedish microbiologist working on how gut bacteria signal the human brain, has stated that he wouldn’t be surprised to find that bacterial signaling acts on pregnant mothers and affects the developing child.

It stands to reason that our modern world’s constant attempts to control and eliminate microbes from our environment can have some pretty disastrous consequences. We have coevolved with a huge diversity of microbes, and in some measure, what and who we have become are predicated on their presence and actions. Take the example of
Helicobacter pylori,
a stomach bacteria that causes ulcers and even stomach cancer. The number of people who are constantly exposed to antibiotics in the meat and milk they ingest continues to increase, and the number of people carrying
H. pylori
in their stomachs continues to decrease. But, as with many members of our microbiome, bacterial actions aren’t all bad.
H. pylori
produces an antacid substance that reduces the incidence of acid reflux, where stomach acid backs up into the esophagus and causes heartburn at best and esophageal cancer at worst. Also, people taking antibiotics to wipe out
H. pylori
have higher levels of a hunger-inducing hormone that may be contributing to the epidemic of obesity in our society. And it’s been shown that people with
H. pylori
in their stomachs have lower risks of getting childhood asthma and allergies. The point is that
H. pylori
can be beneficial—or require antibiotics when it causes stomach ulcers. The key is finding out how to reduce its potential for causing illness and maximize its potential for health benefits. I suspect the key is in flooding the gastrointestinal system with a healthy, diverse mix of microorganisms through ingestion of fermented foods.

The work on
H. pylori
is focused on just one internal microbe, but antibiotics wreak havoc on whole swaths of our microbiome. One study showed that antibiotics altered the levels of 87 percent of the compounds made in mouse intestines by the animals’ intestinal flora. Many of the biological functions that were negatively affected, including the production of bile salts and steroid hormones, are also important for human health.

It shouldn’t be too surprising that the life forms with which we coevolved—big people and tiny microbes—are so closely interconnected. Healthy ecosystems are always in balance, including the ecosystems on and in our bodies. When we big people misuse antibiotics, sterilizing agents, antibacterial soap, and other chemicals that upset nature’s balanced microbial colonies, disease can result. As Rob Knight, a microbial ecologist at the University of Colorado at Boulder, put it in an interview for
Science News,
“Antibiotics are like driving a bulldozer through your garden and hoping that what pops back up is what you want.” My experience with organic gardening shows me that what pops back up is not only not what you want, but is more likely to be what you don’t want: opportunistic rough weeds are always the first to recolonize disturbed soil. There are good reasons for this. The rough weeds, like giant ragweed, pigweed, and lamb’s-quarter, are what’s called C4 plants, while our crop plants, like carrots and spinach, are C3. Without getting too technical, the difference is that C3 plants respond to heat and stress—disturbed soils are generally hotter and drier—by closing their stomata, which prevents the plants from inhaling carbon dioxide or exhaling oxygen. Oxygen thus builds up within the C3 plants and shuts down photosynthesis, stopping their growth. C4 plants have adapted by using a different enzyme to catalyze carbon, one that reduces the buildup of oxygen and allows the plants to keep growing even in conditions of heat and drought. Now, nature not only abhors a vacuum, she abhors bare soil because sunlight, heat, and dryness can harm her precious soil microbes. So she gives the advantage to C4 plants as the first responders when soil is plowed up because they do a better and quicker job of shading the soil with their leaves. That’s why you may plow down garden crops only to find that what pops back up is a lot of ragweed and pigweed.

Similarly, with our intestinal garden. There may well be times when a course of antibiotics is needed, but then the gut is vulnerable to pathogens. So it’s important to keep the gut well supplied with lots of live-culture fermented foods every day during the course of the antibiotic treatment. Yes, most if not all of these microbes will be killed by the antibiotics, but because you are loading more in regularly, the intestines will still be coated with beneficial microbes that keep pathogens at bay.

Just as most landscapes on earth are ecosystems that have not been studied in scientific detail, so our microbiome is still just being looked at. “It’s as if we have these other organs, and yet these are parts of our bodies we know nothing about,” Dr. George Weinstock of Washington University in St. Louis told the
New York Times.
Dr. Weinstock is part of the Human Microbiome Project’s international effort to catalog new species of microbes from our bodies, not by looking at them under a microscope—many of the microbes die off when being transported to the viewing table—but by gathering their DNA. They scraped the skin, swabbed the cheek, and sampled the surfaces at eighteen sites on the bodies of three hundred volunteers. What they get is a jumble of millions of DNA sequences left by hundreds of different species of microbes. How to make sense of it?

That’s what the Human Microbiome Project is attempting to do. First researchers sequenced the entire genome of 900 species of microbes that can be cultivated in the laboratory. From these they discovered nearly 30,000 genes that are unlike any other known genes, which was surprising because these were microbes that could survive the trip to the viewing table and had been studied for years.

The new work is opening doors on a truly multifaceted world of microbial ecosystems in and on our bodies. Dr. David Relman of Stanford University, who’s participating in the project, estimates there are between five hundred and one thousand species of microbes in our mouths alone. “It hasn’t reached a plateau yet,” he told Carl Zimmer of the
New York Times
. “The more people you look at, the more species you get.” And the mouth’s subdivided ecosystem species vary from person to person as well. Only about one hundred to two hundred species live in any given person’s mouth at a given time, but all the rest are available for colonization, and indeed the composition of the mouth’s ecosystems may change widely over time.

The project is demolishing some old ideas as well as highlighting new ones. For many years, the lungs were thought of as sterile tissue, but scientists have now found 128 species of bacteria on the lungs of healthy people. Every square centimeter of lung tissue, it turns out, carries about two thousand bacterial inhabitants. All the microbial permanent inhabitants, all the renters so to speak, and the hitchhikers, plus all the cells of the human body make up the human biome, and so the DNA of all the biome’s creatures, including “us,” is an enormous mishmash, and the total number of genes has to be mind-boggling.

Microbiologists from the University of Puerto Rico recently spent time studying the biome of newborns in a Venezuelan hospital. Those who were born vaginally were covered with microbes from the mother’s birth canal, while babies born by Caesarean section were coated with microbes typically found on the skin of adults—two very different microbial ecosystems. The microbiologists thought that the C-section babies would be sterile, like they are in the womb, “but they’re like magnets,” said Dr. Maria Dominguez-Bello, who was surprised at how quickly the sterile newborns delivered by C-section became colonized.

We’re also finding out that babies born by C-section may be more likely to become obese children than babies born vaginally. A study published in the
British Medical Journal’s Archives of Disease in Childhood
found that babies born by C-section were about twice as likely to become obese as those delivered vaginally—15.7 percent compared to 7.5 percent. Even after accounting for the mother’s weight, the length of time being breast-fed, and the baby’s size, the numbers held up. The study’s authors suggested that delivery by C-section alters the babies’ acquisition of key digestive bacteria in their intestinal flora and that this might be the cause of the high levels of obesity. About a third of the births in the United States are now by C-section, compared to just 20 percent in 1996.

Children born by C-section are shown to be more likely to get infections from methicillin-resistant
Staphylococcus aureus
(MRSA) than children born vaginally, possibly because they lack the healthy gut bacteria seeded in their intestines by the mother’s healthy vaginal ecosystem. C-sections have also been linked to an increase in asthma and allergies, as have antibiotics. Young bodies need signals from internal microbes to fully and properly develop. For instance, mice grown in a sterile environment with no gut bacteria develop stunted intestines.

Scientists are now discovering that certain diseases are accompanied by changes in the biome. Asthma sufferers harbor a different microbial ecosystem than healthy people, and obese people have different gut bacteria than people of normal weight. All this information leads toward the new understanding that when children fail to develop a strong, diverse ecosystem of gut bacteria, their immune systems aren’t trained to fight diseases in the normal way. Their immune cells may too vigorously cause inflammation that damages the person’s body instead of protecting it.

Besides causing trouble, changes in the biome, or at least the intestinal part of it, may support healthy, normal bodily functions, like gestation. Research led by Ruth Ley at Cornell University and published in the journal
Cell
shows that women’s gut microbes become less normal and less diverse as pregnancy progresses. The researchers examined stool samples from ninety-one pregnant women in their first, second, and third trimesters and discovered that changes in the gut bacterial ecosystem that normally cause weight gain and inflammation may actually benefit expectant mothers. As the nine months passed, the pregnant women’s gut bacteria became less normal and diverse. They also found the number of beneficial bacteria declined while the levels of disease-related bacteria increased. The changes were not related to diet.

“By the third trimester,” Ley reported, “the microbiota can induce changes in metabolism.” Ordinarily, these changes can lead to type 2 diabetes and other health problems, but in the context of pregnancy, they’re beneficial because they promote energy storage in fat tissue and help support the fetus. The takeaway from Ley’s study is that our bodies have coevolved with our intestinal flora and that the flora cause healthy changes in the body’s metabolism while the body readies a developing fetus to term.

The colonization of our bodies proceeds throughout life, every day, because we live and move in a torrent of microbes, without which we couldn’t survive. According to scientists taking part in the Human Microbiome Project, human beings on their own produce a paltry number of enzymes that break down plant matter into its constituent nutrients. The wide range of microbes in our guts, on the other hand, have a large arsenal of enzymes that perform this critical function, and they perform it on our behalf.