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The Garden in Your Gut

By Amanda Kolson Hurley
Probiotics and fermented foods are all the rage for digestive health, but do they really work? Here’s what scientists are discovering about the trillions of microbes that live in our bodies and how this complex ecosystem—which some call the “second brain”—influences not just our digestion but our overall well-being.
In the first scene of his tragedy Coriolanus, Shakespeare weaves a vivid metaphor of the Roman republic as a human body, an organism that can’t function unless all its constituent parts work together. The Roman Senate rules this body, but not as its head—as its belly.
The belly, explains a senator in the play to a rebellious commoner, delivers its sustenance to all your limbs and organs, “through the rivers of your blood, / Even to the court, the heart, to the seat o’ the brain.” In the same manner, he says, the Senate “digest[s] things rightly / Touching the weal o’ the common,” then disburses its largesse (as grain rations) to the common people. The moral is that every person in the republic, each lowly finger and toe, owes its well-being to the belly of the Senate. Shakespeare adopted this story from Aesop, who had a fable of “the belly and its members.” 
To modern eyes, the notion that our bellies could rule us seems quaint. We know the incredible power of our brains, thanks to neuroscience. We know that our hearts pump nutrient-rich blood around our bodies. But Shakespeare and Aesop were onto something. Researchers now believe that our digestive systems (or guts, to use the blunt Shakespearean word) play an important and far-reaching role in our health that is still not fully understood. The digestive tract, from the esophagus to the stomach and intestines and down to the rectum, functions less like a simple machine and more like a complex ecosystem. Many scientists have even taken to calling the gut and its microbiome “the second brain” and the legion of microbes that live there “the hidden organ.” 
The human gut is home to a microbial population of staggering diversity. Each of us has 100 trillion microbes in our body at any given time, most of them in our lower intestines. Together, they weigh two pounds or more. The microbial genes in our bodies outnumber our human DNA by a factor of 100 to 1. 
Our gut microbiota—the unique mix of bacteria, viruses, protozoa, and other bugs inside our intestines—influences our weight and likelihood of developing gastrointestinal disorders, like irritable bowel syndrome and inflammatory bowel disease, as well as type 2 diabetes. It could also be a factor in conditions including rheumatoid arthritis, depression, and autism, though research on such connections is still in its infancy. 
Gerard Mullin, an associate professor of medicine at Johns Hopkins University and the director of Integrative GI Nutrition Services at Johns Hopkins Hospital, describes the gut flora as a garden, a “magnificent orchard” of single-cell life. “When I was in medical school, we were told that [gut microbes] were kind of vestigial—they were just there,” he recalls. “I think we’re just starting to understand that they’re vital, and the better their health is, the better our health is.” 

Around 1,000 different species of bugs live in your gut. We acquire them at birth (initially in the birth canal) and during the early years of childhood. What do they do, exactly? 

In his work, Mullin explains the key functions of gut microflora in a layperson’s terms. The bugs break down complex carbohydrates in our food. They manufacture crucial vitamins and other nutrients that we wouldn’t be able to produce otherwise, like vitamin K and niacin. They help protect against pathogens (such as E. coli and Salmonella) and break down toxins. They also communicate with both the immune and nervous systems, sending signals that may influence whether we develop auto­immune disorders and how we regulate our appetite and mood. 
And the bugs talk to each other. Studying how they behave as a community is more productive than looking at this bug or that bug in isolation, says Linda Lee, an associate professor of medicine at Johns Hopkins and the clinical director of the Division of Gastroenterology and Hepatology at Johns Hopkins Hospital. 
“Where people have been very fixated in the past on what the individ­ual organisms are, what seems to be more important is what functions they serve in their bacterial community,” Lee says. 
When we experience problems that are associated with gut microbes, it’s often because the balance of the ecosystem is out of whack. If diversity decreases or the ratio of certain types of microbes shifts, this can cause inflammation, which is connected to insulin resistance, weight gain, troubling GI symptoms, and in some cases, the onset of cancer. 
The digestive tract, from the esophagus to the stomach and intestines and down to the rectum, functions less like a simple machine and more like a complex ecosystem.

As a young man in college, Mullin was morbidly obese and falling short of his academic potential. He wasn’t sure he would be able to achieve his dream of becoming a physician. Then he read a book about the health benefits of fiber. He created his own diet, rich in oat bran, yogurt, seafood, and nuts, and he lost more than 100 pounds. In retrospect, Mullin believes the diet worked because he unwittingly rebalanced his gut microbiota, promoting the growth of friendly bacteria.

Dysbiosis is the term for an imbalance of the gut microbiome. Its causes are elusive, and different for every individual, but diet may play a role. Mullin believes that foods may have an impact on how much systemic inflammation a person experiences, and that inflammation, in turn, seems to promote the growth of fat-forming and insulin-resistant microbes, which further inflame the gut in a dysbiotic vicious circle. Symptoms of dysbiosis include bloating, gas, diarrhea, constipation, and weight gain (or difficulty losing weight). 
One group of gut bacteria called Firmicutes has been associated with obesity. In clinical studies, obese mice were found to have a higher proportion of Firmicutes in their gut flora than lean mice did, and obese people who lost weight were found to have also reduced their share of Firmicutes. A comparison of the microbiota of children in Italy and in Burkina Faso showed that the Italian children, who ate a typical Western diet high in processed carbohydrates and sugar, had a higher amount of Firmicutes. 
Firmicutes digest fiber and turn excess energy into fat. The yin to their yang are Bacteroides, a type of bacteria associated with leanness; not surprisingly, the children in Burkina Faso who ate a plant-rich, low-fat diet were found to have more Bacteroides in their gut flora. 
There aren’t foods you can eat specifically to boost your Bacteroides quotient, but some contend that a healthy diet low in so-called FODMAPs (starchy, sugary foods) may improve the biodiversity of your gut. Those who suffer from irritable bowel syndrome, for instance, are often advised to avoid FODMAPs. Pankaj Jay Pasricha, director of the Johns Hopkins Center for Neurogastroenterology, notes that the links between diet and the microbiota are still being studied. Diets avoiding FODMAPs are premised on elimination. Remove a certain food that causes a reaction such as gas or bloating, and you alleviate the symptom. “That’s different from saying that a FODMAP diet is healthful for your gut,” Pasricha says. “There’s no compelling evidence that this is better for IBS patients than, say, a sensible diet informed by a nutritionist.”
When we experience problems that are associated with gut microbes, it's often because the balance of the ecosystem is out of whack.
The cause of IBS is unknown, but there is a growing suspicion that the gut flora are involved, and that in a subset of IBS cases, the condition may be triggered by an excess of bacteria in the small intestine. Some doctors have started treating IBS patients with the antibiotic rifaximin to control the overgrowth, but as Lee points out, one highly publicized study found that it was only slightly more effective than a placebo. 
For those wishing to improve their gut health, it’s tempting to go all-in on probiotics. But balancing your gut isn’t as easy as eating a lot of yogurt. The diet Mullin recommends to people who are serious about tending their microbial garden begins with a “weeding” phase, eliminating a wide range of foods that can cause inflammation and blood sugar spikes. (This phase also dramatically reduces caloric intake, which is not incidental to weight loss.) Only then does he recommend integrating pro- and prebiotics. “If you throw probiotics at people” without preparing their systems first, Mullin says, “they’re not going to tolerate it well. They might get more bloated.” 
Lee also cautions against viewing probiotics as a silver bullet. “Patients and consumers are being led to believe it’s easy to manipulate the bacterial community by taking probiotics,” she says. In reality, some recommended probiotic strains may be more beneficial than others (there’s a lot that doctors still don’t know about them), and it’s not clear that the same strain will produce the same results from one person to another. 
Some recommended probiotic strains may be more beneficial than others, and it's not clear that the same strain will produce the same results from one person to another.

One gut bug that can be harmful is Clostridium difficile, which causes acute diarrhea, especially in older adults and people who are hospitalized. About 30 percent of patients treated with antibiotics for C. diff relapse. Lee and her colleagues have implemented a new treatment based on a different principle from probiotics: fecal transplants. (Yes, you read that right.) By harvesting gut bacteria from the stools of healthy subjects and putting them in a patient’s colon, doctors replenish the microbiome instead of zapping it. 

“If you restore the bacterial diversity by doing a fecal transplant, 90 percent of the time, their diarrhea will go away,” Lee says. “That is the one disorder where the fecal transplant has been incredibly successful.” Fecal transplant may hold promise for treating other disorders, such as obesity, IBS, and more, though the therapy is still experimental. 
In general, bacteria in the Bacteroides group seem to be associated with leanness and a balanced gut microbiome. But that doesn’t mean every Bacteroides bug is good for us. Take enterotoxigenic Bacteroides fragilis, or ETBF. It causes colitis (inflammation of the colon) and diarrhea. Cynthia Sears, a Johns Hopkins professor and infectious disease specialist, led a study that showed that strains of B. fragilis can trick immune cells into allowing colon tissue inflammation, which precedes the growth of tumors. 
“ETBF was originally identified as a cause of diarrheal disease in young children,” Sears says. “Then, as it was studied in more detail, it was recognized that the toxin that ETBF releases also had other effects on cells, [which] suggested it impacts cancer-producing pathways. … If you colonize a susceptible mouse, the mouse will become chronically infected and will get colon tumors.” In a further study, Sears, working with oncologist Robert Casero, found that B. fragilis alters a gene called spermine oxidase, which causes DNA damage and leads to the formation of colon tumors. 
The ETBF microbe is present in up to 50 percent of all people; simply having it in your system doesn’t mean you’ll develop cancer. What makes some people more susceptible to cancer progression than others isn’t yet clear. 
In a different study, the Sears lab worked with colleagues at Johns Hopkins to obtain colon tumor and polyp tissues and discovered that biofilms—dense layers of bacteria that coat the mucus lining of the colon like pond slime on a rock—were present in the vast majority of growths from the right side of the colon, but not from the left. She’s not sure why that is.
Sears hopes this research will one day help produce an inexpensive tool to identify earlier people at risk for colon cancer. “Colonoscopy is a thousand dollars a pop. That’s completely inaccessible to most of the world,” she says. Screening would probably be based on a stool sample, but Sears admits,“we’re a long way from that point.” Colorectal cancer is the third most common cancer globally, according to the World Cancer Research Fund International. 
Fecal transplant may hold promise for treating other disorders, such as obesity, IBS, and more, though the therapy is still experimental.

Gut microbiota talk to the brain through the hypothalamus–pituitary–adrenal (HPA) axis, a kind of intersystem feedback loop that regulates digestion, stress, immune function, mood, and more. When IBS patients manifest symptoms of anxiety or depression, their doctors may assume that the problem is “all in their head,” but new research suggests that the cause may be signals from their guts—including its microbes—to their brains.

There is also communication within the gut itself, and as the microbiota becomes a topic of intense medical interest, so does a mysterious system known as the enteric nervous system. The ENS lies within the wall of the gut from the esophagus down to the rectum. It has more neurons than the spinal cord and communicates closely with the brain; the ENS uses many of the same neuro­transmitters that the brain does, like dopamine and serotonin. (In fact, more than 90 percent of the body’s serotonin is located in the gut.) 
Pasricha is a globally renowned expert on the ENS who has experimented with using neural stem cells to restore ENS function, among other innovative approaches. Right now he is researching the vagus nerve, which connects the brain and the abdomen. “It’s a major highway from the gut to the brain; it carries signals back and forth,” Pasricha says. Vagus nerve stimulation is already used for epilepsy and depression, though not commonly or with great precision; Pasricha hopes research will lead to a more targeted treatment.
“You can live  without a limb, but you can’t live without your enteric nervous system.”
The enteric nervous system, Pasricha says, “control[s] the movements and secretions of the gut, so that we can process food more or less in the background without requiring conscious effort.” And when you look at it that way, he notes, “it’s the most vital function in the body. If you can’t process food and convert it to energy that you can use, none of the other functions would be possible. You can live without a limb, but you can’t live without your enteric nervous system.”
That’s not quite how Shakespeare put it, but the idea is the same. After all, the belly is “the store-house and the shop / Of the whole body.”  
An illustration of the body's digestive system with a garden growing inside
Illustration by Gaby D'Allesandro

A Guide To Your Gut

Microbiome: the diverse community of microscopic organisms that lives within different “landscapes,” or defined regions of the body—in this case, the human gut. Within each person, there are about 100 trillion microbes in our intestines, including bacteria, protozoa, fungi, and viruses. Their cells outnumber our human cells by 10 to 1. The vast majority of them are not harmful and are essential to our health through digesting the things we eat. Gut microbes are sometimes referred to as “flora” or “microflora,” and the plant connotations of those terms are apt: The microbiota within the landscape of the gut comprises one of the most complex ecosystems on earth, rivaling that of the Amazon rainforest. 

Microbial metagenome: the name for the genetic material within the individual gut microbes. That’s right: The bugs have their own genes. And amazingly, the genes of the microbes in your gut outnumber your own human genes by a factor of 100 to 1. The incredible genetic richness of the gut microbiome is leading some researchers to think about the human body differently, as a “holobiont”—a host organism plus its microbiomes. The human “hologenome,” then, is the sum of human DNA and microbial DNA. 

Probiotics: live microorganisms that are thought to be able to confer health benefits on the host through changing or maintaining the microbiome when consumed in sufficient amounts. Yogurt with live cultures is the most well-published probiotic food, but other fermented foods are thought to have strong probiotic effects: think pickled vegetables (such as sauerkraut and kimchi), miso, and tempeh. It’s important to remember, however, that there is limited scientific evidence for beneficial effects from consuming these foods. 

Firmicutes: a group of gut bugs that has been associated with increased risk of obesity. Studies of mice and humans found that obese subjects had a higher balance of Firmicutes bacteria relative to another kind of bacteria, Bacteroides. We don’t yet know whether Firmicutes contribute to risks of obesity or whether obesity selects for Firmicutes. However, individual species in the Firmicutes group can be beneficial. 

Bacteroides: a group of gut bugs that has been associated with leanness. In studies, lean mice and humans have been found to have a higher proportion of Bacteroides bugs relative to Firmicutes. Bacteroides also appear to play a role in early infant development. Some members of the Bacteroides family can induce infections.


Could the gut microbiota influence how our body handles toxins?


That’s the question Ellen Silbergeld, an environmental health professor in the Johns Hopkins Bloomberg School of Public Health, asked in a recent paper. What Silbergeld and her co-author, Rodney Dietert at Cornell, hypothesized was radical: that the prevailing environmental health model of how exposure to toxins leads to disease ought to be altered to include the role of the microbiome. 
Experts used to assume that different populations reacted differently to toxins based on genetic variations. But the microbes in your body also have their own genes. Could variations arise not from our DNA but from the genes in our gut microbes? 
Silbergeld and her co-author write in Toxicological Sciences that “it is increasingly unlikely that human genes are the only genetic deter­minants of individual or population differences in terms of toxicity or disease risk based on our new understanding of the microbiome.” 
The example they cite is arsenic. Its impact on populations varies based on the metabolism of arsenic, which researchers have long attributed solely to human genes and polymorphisms in these genes—but within our gut microbiomes there are organisms that have the same genes that metabolize arsenic, too. Maybe the variations are at least in part in the micro­biome rather than in our human genome.  It’s an idea that Silbergeld has plans to test with colleagues at the Bloomberg School of Public Health.   
“One can propose that there are these interactions, that the microbiome is the gatekeeper, but how big a role does it play? Nobody knows that yet. All these different research projects at Hopkins are really directed at determining the extent to which we need to consider that our genome includes the metagenome of our microbiomes.” 

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