Can You Change Your Microbiome?

“I can’t believe it—he’s a chatterbox!” Samantha Jones* shrieked with delight.

Her autistic son was typically quiet, nearly non-verbal most of his life, but a microbiome-augmenting treatment had drastically improved the child’s behavior—like the flip of a light switch. Jones’s child was part of a study that examined the role that microscopic critters living inside us, collectively known as the microbiome, can play in gastrointestinal issues and autism. While the study was small, it suggests that altering our microbes can have wide-reaching consequences—sometimes for the better.

Enterobacteriaceae bacteria are commonly found in people's intestines.

Our microbiomes dictate more about our bodies and our lives than we may like to admit. The influences range from the obvious, such as intestinal health, to the surprising, such as our moods. When microbiome-augmentation coincided with Jones’s child going from nearly non-verbal to conversational, it hinted at the astounding authority microbes can wield over human wellness.

The science is anything but settled, though. After years of connecting the dots between microbes and human health, scientists have begun using microbes for medicine—but is it precise enough, and at what cost? And can we use that knowledge to alter our own microbiomes for the better, even if we aren’t sick?

It wasn’t up until the late 1990s that microbial ecologists turned their attention to people and unearthed a microbial symphony within.

Research efforts accelerated in 2008 when technology developed by the Human Genome Project made it easier to identify microbes by rapidly sequencing their genetic material. The diversity those tests revealed was startling: Scientists now estimate that roughly 1,000 distinct microbe species have evolved specifically for living in the human body, and a healthy person’s microbiome contains combinations of hundreds of different species—making your microbiome unique like your fingerprint.

Links between microbial diversity and human health have been multiplying. Animal studies have helped scientists understand how the microbiome may influence a vast array of diseases, including irritable bowel syndrome, anxiety, immunity, schizophrenia, obesity, and more. Scientists were amazed when transplanting microbes between social and hermit-like mice led to personality swaps. A similar study found that transplanting microbes from an obese human to a mouse resulted in the mouse gaining weight. From nearly every health angle, the long-overlooked microbiome seemed to play a role.

Studying microbes in humans, however, has been challenging. Since each person’s microbiome is unique—even if two people have similar lifestyles and health histories—it’s difficult to make broad comparisons.

Still, a general trend has stood out—healthy people harbor more diversity in their guts.

That would seem to suggest that adding “good” microbes to our bodies via probiotics would lead to major health benefits. In theory, this could be as simple as eating yogurt or swallowing a pill.

Unfortunately, consuming microbes doesn’t necessarily mean they’ll reach your intestines alive. The human body is designed to annihilate microbial intruders—germs and probiotics alike. When you eat probiotic “live culture” yogurt, for example, stomach acid digests most microbes along with the food.

Shigella bacteria can evade the body's defenses and infect the large intestines.

To make matters worse, microbes suited to live in your intestines need accommodations to survive from the factory to your mouth. Dr. Geraint Rogers, director of microbiome research at South Australia Medical Research Institute, says it’s hard to tell whether over-the-counter supplements provide accommodations that work. “Charlatans can pick some bug off shelf that already has FDA approval, stuff it into pills, and cite the science for health benefits, but these are anaerobes—they can’t survive with oxygen. If you analyze the pills, most have nothing in them that’s viable,” Dr. Rogers says.

Even the probiotics that manage to reach your intestines don’t do much for long. Microbiologists speculate that our microbiomes don’t necessarily have vacancies for new members. By default, most probiotics that reach your intestines behave like tourists—they stay a little while before moving on to the next destination (in their case, the toilet).

So how is it that, despite these long odds, some probiotic foods still appear to offer health benefits?

A research group in Madrid, Spain sought to answer that question while studying the link between probiotic yogurt and mental health. After participants dieted on either live culture yogurt, dead culture yogurt, or no-culture yogurt, they were scored for mental health (responses to sadness, rumination of sad thoughts, and feelings of anger or frustration). Regardless of whether probiotics were dead or alive, scores improved when participants dined on culture yogurts. Yogurts lacking microbes, however, conferred zero benefits, so what changed?

One explanation is that culture foods contain prebiotics—compounds that act like fertilizer good microbes inside you and food to fuel their beneficial activities. Oftentimes, microbes take food your intestines haven’t absorbed and convert it into something useful. Dietary fiber, for example, is good for your gut because microbes break it into smaller compounds that nourish and energize your intestinal lining. The byproducts from feeding microbes dietary fiber also seem to reduce type 2 diabetes risks and inflammation. Snippets of protein can be converted into an array of neurotransmitters—chemicals that directly influence our brains and nervous systems—and these byproducts appear to improve people’s moods. Gut microbes also use leftovers to make compounds that stabilize your immune system and can neutralize carcinogens from red meat.

One option for enhancing your health via the microbiome is adjusting your diet.

Somewhat anticlimactically, this translates into a dietary strategy that’s old news: eat less fat, more vegetables, and more fruit. However, this can be challenging for creatures of habit; for decades we’ve been instructed to eat more fruit, more vegetables, and less fat to prevent obesity—yet the WHO reports that obesity has tripled around the world between 1975 and 2016. Given that dismal trend, Dr. Rogers thinks it’s unlikely people would change their dietary habits for their microbiome.

Which is why microbiome researchers have devised a dietary loophole: prebiotics in pill form. Consider red meat: In spite of increasing colon cancer risks, most people are reluctant to write-off the staple of Western diets altogether. There may be a way to counteract our irrational choices, though. A recent clinical trial demonstrated that consuming a pill stuffed with a corn derivative fueled microbe activity that returned carcinogens back to a healthier baseline.

There are also instances where an unhealthy microbiome isn’t the result of questionable choices but bad luck.

Consider a cancer patient whose microbiome was completely ablated from chemotherapy or an elderly person whose microbiome is inexplicably dwindling with age or an infant born deficient in microbes.

For some desperately ill adults, this is often where fecal transplants come into play, where microbes from a healthy donor are transplanted into a sick patient. Unlike probiotic supplements, fecal transplants are classified as a medical treatment, and doctors can be sure the transplanted microbes reach the intestines alive. Dr. Monika Fischer from Indiana University is one doctor who uses fecal transplants to treat her patients. She administers the bright blue capsules, lovingly called “poop pills,” to patients suffering from C. difficile infections. Fischer cites research approximating “33 billion colony forming units” being enough to “repoopulate” the recipient’s intestines. Strength in numbers—and the fact that the pills are kept frozen under exacting conditions—may be why fecal transplants work where other probiotic treatments fail. Follow-up studies have confirmed a subset of transplanted probiotics have persisted up to one year after treatment.

However, Dr. Fischer acknowledges that beyond C. difficile infections, one-time fecal transplants often aren’t enough for a microbiome reset. Irritable bowel syndrome patients, for example, don’t retain probiotics long-term, and must take the pills every other day to sustain health benefits. Dr. Fischer attributes the difference to divergent intestinal landscapes. “A C. difficile patient is a very unique case scenario, having a very diminished microbiome…Normally you have a healthy ‘forest’ in the gut. After C. difficile, the forest looks like a war zone—there are very few trees left.” Dr. Fischer says.

Though C. difficile infections may be unusually responsive to fecal transplants, the approach has inspired other promising treatments. For example, Dr. Rose Krajmalnik, a researcher studying the link between our guts and autism, took a page from C. difficile research and then took a calculated risk. To ensure her therapy worked long-term, she deconstructed her patients’ microbiomes and replaced them with a curated assortment of donated microbes. In a clinical trial aimed at treating autistic children with preexisting GI tract symptoms, Dr. Krajmalnik and her colleagues were able to reduce GI symptoms by 82%, and the destruction of the microbiome made room for new, beneficial species to grow and take foothold. They also observed 20-25% improvements in autistic behaviors: hyperactivity, anxiety, and speech patterns, among others. Somewhat miraculously, the treatment resulted in no negative side effects.

Microbiome replacement isn’t without risks, though. “I do not want people to do this at home without (medical) supervision, because it could lead to bad GI infections… and the results might be different depending on what microbe donor you use,” she says.

If fecal and microbial transplants therapies are the present, Dr. Rogers predicts that synbiotics—a combination of synergistic probiotics and prebiotics—are the future.

Even if microbiome transplants work, there is still a very real risk for infections from microbe donors. To get around these undetectable risks, synbiotics combine microbes, metabolites, and fiber in a more controlled pathogen-free manner. “As glamorous as it sounds, we can build poo in the laboratory, and install that into people.” Dr. Rogers says.

Synbiotics have already demonstrated some promise in India, where researchers gave synbiotics to roughly 4,500 premature babies during the first few days of life. The synbiotics greatly reduced instances of sepsis and mortality.

Want to learn more about microbes? Tune into “NOVA Wonders: What’s Living Inside You” premiering May 2, 2018.

For more subtle effects, like managing anxiety and minor weight loss, it’s still too early to say whether any microbiome-augmentation benefits would be significant, or if they exist at all.

“The microbiome could be argued to be one of the most important health and medical frontiers that we’ve reached for a long time,” Rogers says. “You can pay to have somebody analyze your microbiome,” but the increased self-obsession isn’t necessarily a fruitful endeavor. If you have the time and leisure to worry about your microbiome, Rogers says, “odds are you don’t have anything to worry about.”

In the meantime, perhaps we should settle for some old advice supporting this unfolding health frontier—eat more vegetables, less fat, and, yes, exercise.

*Names have been changed to protect patient privacy.