The next time you use alcohol gel or a wet wipe to sanitize your hands, you should give the amazing world of microbiomes some respect. Although our bodies are composed of some 10 trillion human cells, there are about 100 trillion bacteria on skin and inside our bodies – suggesting, perhaps, that most of each of us is not really us.
Humans have about 20,000 human genes, but the microbes inside us have an impressive two million to 20 million genes.
All the different bacteria in our bodies weigh about 1.5 kilos, which is equal to the weight of the brain and slightly less than the liver. Bacteria live with us from the time we pass through our mother’s birth canal (but if we were born by cesarean section, different bacteria reach us from her skin) until death.
They are single-celled organisms with a round, cylindrical or spiral shape; may be beneficial or harmful; can live in the ocean, the earth or in our small intestine, eyes, mouth, stomach, sexual organs and on the skin. Although they all look pretty much the same, scientists who studied their genes now know that there are thousands of different kinds of them. The types differ depend on where they live in the human body, where you live, what you eat, your placement among your siblings, how many sexual partners you have had and other criteria. While some bacteria may improve your digestion and educate your immune system, others may trigger overweight, rheumatoid arthritis, autism, acne and depression.
THESE ARE some of the facts presented by Prof. Rob Knight (and science journalist Brendan Buhler) in the 2015 Simon & Schuster book Follow Your Gut: The Enormous Impact of Tiny Microbes that has just been translated in Hebrew by Yedioth Aharonoth Books (NIS 61). The 151-page translation by Shlomit Cnaan has been titled Tehushat Beten: Hashpa’atan Ha’atzuma Shel Haidakim Ze’irim. The compact volume is easy and even fun to read, backed with many footnotes and full of tongue-in-cheek humor.
The University of California at San Diego medical ecologist completed a bachelor’s of science degree in biochemistry at the University of Otago in New Zealand, where he was born, and a doctorate at Princeton University on the origin and evolution of the genetic code. In 2014, he moved from the University of Colorado at Boulder to teach and conduct research in California on the ecosystem of microbes. His reason for studying the subject, as he told Nature in 2012, is “how understanding the microbial world might help us improve human and environmental health.”
While at his Denver university, Knight co-launched a project called American Gut, an effort to map the unique microbiome of the US using open-access data mining tools and citizen-scientists to discover how lifestyle and diet affect Americans’ internal flora and fauna and general health. In a TED (Technology, Entertainment and Design) talk before a large audience in 2015, Knight said that more than 8,000 people had registered, sent in fecal samples and allowed a lab to sequence the DNA of their microbes and then send the results back to them. He even handed out some of his kits to people in the audience to use at home.
“IT’S WORTH noting that just because we know a microbe is involved in a specific disease, it doesn’t mean the answer – or the cure – is to eliminate that microbe,” he wrote in his seven-chapter book.
“In fact, doing so might cause irreversible damage. It may turn out that targeting diet or inhibiting an enzyme (a protein that speeds up a particular chemical reaction) might be more effective than attacking the microbes directly. And yet the reason there is so much excitement about the microbiome is the prospect of discovering entirely new mechanisms to treat conditions that have resisted existing therapies.”
Being exposed to dangerous bacteria doesn’t necessarily lead to being infected yourself, writes Knight.
“Actually, our risk of sickness depends on a combination of exposure, genetic makeup and other factors. Some people are born with resistance to certain diseases. You’ve probably heard of Typhoid Mary, a New York cook in the early 20th century who carried the bacteria that causes the disease typhoid fever.
She infected family after family with her excellent cooking that was laced with a dose of her not-so-excellent microbes. But Mary was never sick.
She was naturally immune to the fever she carried inside her… We’ve learned that susceptibility to essentially every kind of infection hinges greatly on genetics. And mouse versions of Typhoid Mary are easy to create in the lab – not just for typhoid fever but also for a whole range of other infections. It’s proof that our genes influence which microbes make each of us sick.”
In inflammatory bowel disease such ulcerative colitis and Crohn’s disease, there is a changed relationship between intestinal microbes and the immune system.
“Your body goes to war with all the creatures in your intestines, and the intense pain, bleeding, and all-too frequent trips to the toilet are the collateral damage.”
In all these conditions, certain microbes increase in number. One typical sign of these diseases is an increase in the abundance of certain bacteria.
“What’s particularly interesting is that the microbes in patients do not appear to be behaving normally: their metabolism is off; they’re eating and secreting different chemicals.
We don’t yet know if this altered behavior is caused by the body’s immune response or if microbes are at fault… “It’s also not clear yet if these inflammatory bowel diseases are caused by a change in the microbiome or if there is something in the genes of the afflicted person that causes the body’s normal relationship with gut microbes to go awry, and the changes in the microbial population are merely a response.”
As for celiac disease, people are unable to digest the gluten protein, which activates the immune system, which attacks and shreds the lining of the gut. Celiac was originally identified and named by the Greek physician Aretaeus of Cappadocia in the first or second century CE, Knight writes.
“ But it wasn’t as widely known until Dutch physician Willem-Karel Dicke observed in the “Hunger Winter” of 1944-45 during World War II that when wheat was unavailable, his celiac patients survived much better.
“So far, studies have not shown consistent trends linking microbes with celiac. Although many studies are able to find differences between the microbiomes of celiac patients and healthy people, the bacteria in the celiac patients differ from study to study. Clearly the pattern is complex, and more work is needed to understand whether gut bacteria contribute to celiac or simply respond to the altered, gluten-free diets of celiac patients,” he writes.
A BRITISH researcher found in the 1980s that later siblings in larger families tended to have lower rates of hay fever and related allergies. This may result from catching infections from older siblings that help train the immune system to target real invaders rather than dust mites.
“This idea, known as the ‘hygiene hypothesis,’ essentially suggests that keeping ourselves too clean can lead to immunological problems, as our idle immune systems – unchallenged by the bacterial and viral pathogens that humans co-evolved with – get restless. You still shouldn’t challenge your kid’s immune system by encouraging them to eat tainted meat or lick a hospital floor,” he writes with humor.
He also explained the mystery about why some people attract mosquitoes while others do not. Mosquitoes are deterred by the type of bacteria on the skin on some people but are attracted to other bacteria as to a magnet. His wife Amanda has proven very tasty to the biting bugs, while Knight himself is a turnoff.
“Until a trip to Peru in 2008, I used to weigh quite a bit more. Amanda and I hiked the Inca Trail and then spent a week in the Amazon, where we both came down with really nasty diarrhea – not what you want when you’re in a tent. We recovered, only to both have it flare up again.
To treat it, we both took doses of the same antibiotic. When we got home, we resumed more or less the same diets and exercise patterns we’d had before we left for the trip. However, I lost about 80 pounds in a few months, going from obese to a healthy body weight,” he recalled.
“The difference was remarkable.
I had to buy new pants, and colleagues took me aside to ask if I had cancer or if there was something else they should know about. In contrast, Amanda lost no weight at all.
I believe that the difference was related to a radical change in my microbes: we each responded differently to the same disease and the same course of treatment.”
Allergies, asthma, obesity and acne are just a handful of the conditions that may be caused – and someday cured – by the microscopic life inside us. The key is to understand how this groundbreaking science influences your health, mood and more, Knight suggested.
THE AUTHOR noted that a decade ago, a person who wanted to know what his personal microbiome consisted of would have to pay $100 million. Today. A patient today can order one for just $100. In the near future, he predicted, a microbiome survey will become routine at the doctor’s office.
When Amanda gave birth to their daughter by cesarean section, Knight made sure to smear bacteria from his wife’s vagina on the newborn baby, which he said, protected her from all infections at least until she was a toddler. While this benefit is anecdotal, Knight conceded, it was worth doing this for other infants born by emergency C-section – and the idea is in fact being tested in clinical trials.
There are entirely different colonies of bacteria in different parts of the body, he continues, and while all humans have 99.99% identical genes, the differences among microbiomes vary so much that scientists could accurately identify the computer mouse used by one person and differentiate it from the mouse used by another. There are even different bacteria on the right side of a person’s keyboard than on the left side of the keyboard, he continued.
Knight also explains prebiotic (substances that enhance and benefit our microbes) and probiotics (microbes that live in and benefit the human body).
As for antibiotics, the author notes that many people have no fear about taking antibiotics, which can cause people complications if taken unnecessarily and create resistance of bacteria, making them much less effective.
But these same people are afraid to take vaccines, which usually are much safer. Antibiotics can destroy whole colonies of beneficial bacteria as well as destroy harmful ones. Fortunately, the original colonies in the gut usually come back.
Working on lab mice, Knight believes that bacteria can cause obesity and be used to create weight reductions. He and colleagues “haven’t been able yet to design a microbe community that actually slims down a mouse (or a person), although that’s certainly the goal. However, in yet-unpublished research, other groups have reported using antibiotics to target the bacteria that proliferate on a high-fat diet, successfully slimming down the mice even if they still ate unhealthily. It’s exciting to think that we could grow ourselves healthier and leaner microbiomes by altering our diets.”
FECAL TRANSPLANTS have become known in recent years to treat those suffering from severe infections with Clostridium difficile bacteria and the resulting diarrhea that requires them to defecate up to 20 times a day. After antibiotic therapy has failed them, they are eligible for fecal transplants (from the top or the bottom) via healthy donors. This, says Knight, causes their diarrhea to disappear.
And what about the future? The author suggests that microbiome tests will predict how individual patients will react uniquely to pain relievers, cardiac drugs and even artificial sweeteners. The understanding of the reactions of the body, including its bacteria, to diets and physical activity, will deepen. Fecal transplants will become more common, but they may require more exact matching between the donor and the recipient. But a “fecal pill,” he suggests with humor, “will excite only bacterial scientists.”
In the longer term, it could be possible to create colonies of bacteria that protect humans from obesity, just as scientists have already been able to do in mice. Scientists may perhaps be able to create bacteria living on the skin that repel mosquitoes (Amanda, he says, will surely be eager to have them).
Could bacteria be used not only for diagnosis but also to cure them of a wide variety of diseases? Knight believes that his American Gut project could potentially do this.