You're Home to Trillions of Microbes That Affect Everything From Digestion to Depression

Researchers said this week that mice who'd received fecal transplants from depressed humans exhibited signs of "depressive-like behavior," indicating that depression may be one of the many things influenced by the trillions of microbes in our guts — which of course, wind up in our bathroom business.

The microbes living throughout your body -— microscopic organisms including bacteria, fungi, and viruses that are invisible to the naked eye — weigh as much as your brain and may outnumber your own cells by 10 to one, though some scientists have questioned that number. But don't be turned off by these ever-present "germs." Without them, you wouldn't be able to digest food, keep out harmful pathogens, control inflammation or, you know, stay alive.

And as microbiome science really gets going thanks to technology from DNA sequencing that's arisen over the last decade, researchers are learning that the microscopic critters could play a role in everything from obesity to multiple sclerosis to autism to cancer.

"It's really a field at its infancy," said Dr. Jeffry Katz, medical director of the inflammatory bowel disease center at University Hospitals Case Medical Center in Cleveland, Ohio. "But there are lines of evidence, some from animal models but also some human evidence, that the gut bacteria are going to be very important for a number of human health conditions."

Humans are sterile in the womb. They are first colonized by bacteria and other microbes when they exit their mother's birth canal. Over the first few years of life, the microbiome develops alongside the immune system, and by age two, the mature microbiome is set, said Lita Proctor, PhD, who directs the National Institute of Health's Human Microbiome Project, which began in 2007 to develop tools and datasets to better understand the microbiome and its place in human health.

Thousands of species of microbes exist throughout the body, including on the skin, up the nose and in male and female genitals, but its "ringmaster" exists in the gut, Proctor said. The human microbiome has about the same rate of metabolism as an organ (the liver), and the microbes reproduce so quickly that half of the dry matter in stool is discarded microbes.

In the large intestine, microbes play a huge role in digestion. In fact, you don't have the enzymes to digest most plants, but the microbes in your gut do that for you. They also make certain vitamins, Katz said.

Temporarily altering the microbiome has also proven to be effective medicine. Fecal transplants — in which a solution containing donor stool is introduced to a sick patient via colonoscopy, enema, or tubes that go up the nose and into the gut — have been successful at temporarily changing patients' microbiomes to rid them of infections like Clostridium difficile, a tough-to-cure diarrheal disease.

Given the ringmaster microbiota's location, it is thought to play a role in obesity.

"There have been mouse studies where people take the microbiomes of obese people and introduce them into mice, and those mice go on to develop obesity," she said, adding that it's important to remember that obesity in humans is complex and developes over time.

A 2013 study published in the Journal of Clinical Endocrinology and Metabolism concluded that humans with higher levels of hydrogen and methane in their breath, indicating that their guts were colonized with Methanobrevibacter smithii, were likely to have higher percentages of body fat than people without this gut bacteria.

"It's become clear that what we eat affects gut ecology," Katz said. "There's a lot of discussion of the modern western diet. Part of the reason it may be making us less healthy in some ways is because of the way it promotes growth of different bacterial populations."

The microbiome can change on a vegetarian diet, but the microbes return back to normal soon after meat is reintroduced. So far, scientists haven't figured out how to change the microbiome for good.

There's also research to suggest the gut microbiome can influence mood, as detailed in a study using mice who received those fecal transplants in a a study published this week in the journal Molecular Psychiatry. Another study published last year in the journal Cell concluded that serotonin, a neurotransmitter that affects sleep, mood, and sexual desire, is mostly made in the gut, and that microbes play a role in its production.

"The gut microbiota produces a lot of neurotransmitters," Katz said, referring to chemicals that send messages throughout the nervous system to the muscles and glands. "We haven't figured out what the mode of communication is, but there's a gut-brain axis in which the microbiome plays a major role."

In autoimmune diseases like multiple sclerosis, rheumatoid arthritis, and even lupus, scientists have found differences in patients' microbiomes compared with healthy individuals, Jason Kubinak, who will assume professorship in June at the University of Texas, Arlington, said.

The theory is that because humans put too much of an emphasis on being "clean," they hinder the microbiome. This may also be why so many children are diagnosed with allergies.

"We're not allowing our children's immune system to develop properly," Proctor said. "If we don't have rich microbes to act as part of the microbial system, the immune system starts acting on itself."

Multiple sclerosis, in which the immune system attacks the nerve fibers' protective sheaths, interrupting messages between the brain and the rest of the body, is especially interesting because scientists are still trying to figure out what triggers it, Kubinak said.

There's also research to suggest that gut bacteria may play a role in diabetes, a disease in which the immune system attacks isolated cells in the pancreas, causing them to stop producing insulin, which regulates blood sugar, said Kubinak, who conducts mouse model studies pertaining to microbiome and autoimmune diseases. In mice, certain microbes are thought to protect against diabetes.

Microbes may play a role in autism, a developmental disorder that affects one in 68 children, but the research is still very new.

"Autism is the one a lot of people are starting to get particularly interested in because several studies found a link between the microbiota and autism development," Kubinak said, adding that most of the studies linking autism and microbes in the body were done in mice rather than humans, which means they should be taken with a grain of salt.

Though mouse studies are a crucial part of medical research, the results aren't always the same when mouse studies are repeated in larger mammals and humans. And since autism is tough to diagnose in humans, it would be even more difficult to measure in a mouse.

There's no blood test for autism, so doctors are called upon to determine whether their human patients have difficulty communicating and responding to social cues, for instance.

"How do you measure autistic behaviors in a mouse? I would venture a guess that it's difficult," Kubinak said.

Still, Kubinak said there are human studies in which researchers found differences between the microbiomes of siblings who were autistic compared with those who were not autistic, signalling that clues about the disorder might be in the gut. But it's still early days for this research in humans.

Having an unhealthy microbiome has been linked to certain cancers. This is thought to be tied to the microbiome's role in inflammation, which is known to trigger cancer growth.

Scientists are studying the microbiota's relationship to colorectal and esophageal cancers. Fatty liver disease, dementia and coronary artery disease may also have roots in the microbiome, Katz said.

"There's lots of tantalizing theories and ideas, but less good human proof of any of this," Katz said, explaining that many links have only been found in animal models so far. "We're going from a time when we just ignored bacteria to a time when we're trying to understand how it interacts with our body as a whole to promote health or make us sick."

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