How the Gut Cures and Creates Disease

In this series, “Cultivating Our Gut Microbiome to Stifle Disease,” we’ll share how the latest developments on this medical frontier are transforming our approaches to illness and offering new strategies to heal and prevent disease.

The viruses, fungi, and bacteria that live inside and upon us are essential to critical functions in our bodies. Microbes in our mouths help us create nitric oxide, for example, helping keep heart disease at bay by ensuring our blood flows smoothly. This microbial community, our microbiome, is barely understood, but what we do know tells us that it is key to preventing and curing many diseases. Nowhere is this flora of microscopic life more crucial than in our gut.

Gut health is about much more than basic digestion. The beneficial bacteria that live within the gut help us digest foods in our large intestines and turn nutrients into metabolites that influence both our physical and mental health.

Metabolites are usually small molecules produced through metabolism. That metabolism may be done by our cells or by our microbes. Among other things, “microbial metabolites influence immune maturation, immune homeostasis, host energy metabolism and maintenance of mucosal integrity,” notes a research review published in Nature Reviews: Gastroenterology & Hepatology. “Some bacteria produce bioactive neurotransmitters,” notes a study published in Nature. Bacteria in our gut contribute amino acids, lipids, and sugars linked to processes such as digestion and circulation. Metabolites are also involved in synthesizing hormones.

Our gut microbiome is a dynamic environment with trillions of microbes constantly interacting with us and one another. Bacteria have a short lifespan, yet they adapt quickly, and their numbers can proliferate rapidly to vastly improve our health—or damage it in ways that researchers can’t comprehend.

A New Medicine

The human microbiome is a frontier of modern medicine in which many scientists and researchers expect to find explanations—and perhaps treatments—for the rising numbers of autoimmune diseases. As the human body increasingly turns on itself, the need for new treatments, cures, and answers grows more urgent.

The composition and changes among gut microbiota have already been associated with diseases that range from gastrointestinal, inflammatory, and metabolic conditions to neurological, cardiovascular, and respiratory illnesses.

Our microbes also have a significant impact on other pathogenic microbes. Each microbiome reacts uniquely when attacked by viral pathogens, for example. This can help explain how families can have some members who become sick from illnesses such as COVID-19 and influenza and others don’t.

For doctors and researchers, it’s a complex puzzle full of promise.

“We care about the biome, of course, because we believe hopefully that we can promote health by altering or intervening in a biome, and that’s sort of a core question,” Dr. Neil Stollman, chairman of gastroenterology at Alta Bates Summit Medical Center, said at the recent Malibu Microbiome Meeting, a conference on the microbiome.

For the most part, precision treatments based on our individually complex microbiomes are still years, or even decades, away. But the picture of the microbiome’s role in disease is much less murky than it was a decade ago.

Microbes and Disease

A 2019 review in Microorganisms examined several studies that looked at the way the ecosystem of the human microbiome changes as we age. The study sought to document ways the microbiome shifts in response to habits, diet, exercise, and diseases. The simplistic conclusion is that a healthy balance of microorganisms allows the body to perform metabolic and immune functions that prevent disease development.

If that healthy balance is lost, it can be much like an ecosystem that has lost too many crucial plants or animals and faces collapse, or can’t deal with an invasive species that then wreaks havoc. When this happens with the microbiome, it’s called “dysbiosis.”

Dysbiosis is connected to diseases ranging from gastrointestinal conditions to metabolic and neurological disorders. Research has also linked the gut microbiome with cardiovascular disease, asthma, allergies, eczema, and nonalcoholic fatty liver disease, according to a 2021 article in the European Journal of Clinical Nutrition.

Whether disease causes the imbalance or the imbalance causes the disease requires closer examination. The number of possible disturbances is a growing area of research, too.

Microbes and Viruses

“Commensal bacteria calibrate the activation threshold of innate antiviral immunity,” declares the title of a study (pdf) published in the journal Immunity in 2012. In other words, these bacteria prime the immune system to protect the body from viral replication, severe illness, and death. The study pointed out a loss of commensal bacteria is associated with severe illness and mortality in influenza, and that treatment with probiotics is beneficial in viral gastroenteritis and viral respiratory infections.

Even more recently, the relationship between microbes and COVID-19 illustrated the potential for bacteria to confer protective immunity against viral infections.

Dr. Sabine Hazan, a gastroenterologist and researcher, explained at the recent Malibu Microbiome Meeting her research findings that illustrated high levels of Bifidobacteria appear to create a protective factor against COVID-19.

The “Lost microbes of COVID-19” study that she led examined the varied responses to COVID-19 within families of close contact and concluded lower levels of Bifidobacterium were associated with infection. One unknown is whether the bacteria was lower because of infection or if the subjects had previously low levels of Bifidobacterium that made them susceptible to COVID-19.

Because viruses are known to penetrate an altered biome, Hazan postulated that the prevalence of dysbiotic (imbalanced) microbiomes in America could explain why COVID-19 hit so hard here.

“Maybe it’s about the lost microbes that made us susceptible to COVID. We’ve lost those bifidobacteria, and we need to replenish them,” she said. “The microbiome tells the story. It’s the forensics of medicine.”

Future studies could determine what commensal microbes could be used therapeutically to boost natural viral resistance, a 2020 study in Cell suggests. Researchers envision a future where the microbiome is leveraged not just as a diagnostic tool, but also to intervene for desired physiological effects.

Microbes and Health

Of course, as researchers look toward an exciting future full of possibilities, they’ve also realized the importance of figuring out how microbiomes have become dysbiotic. Many researchers are asking what lessons can we apply to prevent disease in the first place.

We now know that the process of populating our microbiome starts during birth, when newborns receive bacteria from their mothers that help them prevent harmful, opportunistic bacteria from colonizing in the baby’s microbiome. And as we age, we acquire microbes in two ways: vertically (from parents), or horizontally (from the environment, including food).

The vertical formation of our microbiome likely begins in the womb, although the research is preliminary. In other words, we get some microbes from our mothers before we are born. Some research suggests we also collect other microbes as we make our way through the vaginal canal during birth, though recent findings dispute this. Our close proximity to our parents, as well as breastfeeding, also confer microbes.

Research finds babies born by cesarean section delivery or who have early antibiotic exposure are more likely to suffer from inflammatory diseases and obesity, which is likely linked to dysbiosis. “Vaginal seeding” is one strategy to immediately recover a baby’s microbiome to a more normal ecology, although the procedure is still in question.

During this simple procedure, a sterile gauze is inserted into the mother’s vagina prior to C-section delivery and then wiped over the newborn’s entire face and body in an attempt to replicate microbe exposure in a vaginal birth.

There’s been some controversy associated with the procedure since the mother could be harboring pathogenic microbes or even viruses such as COVID-19. The U.S. Food and Drug Administration considers vaginal secretions a “biologic,” subject to new drug regulations.

Studies are underway to determine if this would be an effective public health strategy to improve health outcomes. It might potentially open the door for “live biotherapeutics,” a standardized donor product for those babies whose moms might be suffering from infection or diseases.

Bifidobacterium is one of the first bacteria to colonize the gastrointestinal tract, and is believed to have many health-promoting effects. Bacterial diversity rapidly expands in a baby’s first year of life, slowing by age 3 and becoming more similar to an adult’s by age 5.

Still, the gut microbiome of a child is less diverse and remarkably different from that of healthy adults. As we age, we begin acquiring microbes horizontally from environmental sources such as food, other people, and animals.

As much as our microbiome is exposed to bacteria and other microbes that help form it, it’s also shaped by environmental exposures that can kill off some flora and cause others to proliferate.

Because we understand so little about the microbiome, it’s hard to know what exactly a healthy balance of microbes looks like. Researchers are trying to figure out if there is a gold standard microbiome or even a normal one.

Next: Scientists now grapple with the seemingly impossible task of creating a standard for the ideal microbiome. Scott Jackson from the National Institute of Standards and Technology explains how human bias can complicate research. 

Previously: Many of the most important medical advances of previous decades were based on containing the threat of infectious disease. Unfortunately, more recent research has revealed this war against microbes also is killing beneficial microbes essential to human health. Read Part 1- Killing Bacteria with Antimicrobials and Antibiotics May Be Shortsighted, According to New Science About the Microbiome