2 Strange Ways Medicine Is Manipulating the Microbiome

Desperation to fix gut dysbiosis is driving solutions using stool and synthetic microbiomes

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The human microbiome is a vast frontier of known and unknown microscopic creatures carrying out untold biochemical transformations for metabolic pathways we have yet to map out.

Trillions of microbes—including bacteria, viruses, and fungi—interact with human physiology, outnumbering human cells. Most microbes are “friendly,” and among their functions is keeping the disease-causing pathogenic ones from creating problems. Pathogenic bugs occasionally cause acute illnesses and play a role in chronic diseases.

But sometimes, even the ones that live in harmony with us and one another—called commensal microbes—depopulate into harmful ratios. Anytime the ratios are believed to be unhealthy, it’s called dysbiosis, a condition believed to be driving inflammation and autoimmune disease.

Research is rapidly cataloging various microbial demographics associated with diseases such as autism spectrum disorder, Parkinson’s disease, Crohn’s disease, Alzheimer’s disease, various cancers, cardiovascular disease, and others.

Against a backdrop of increasing disease rates, the concept of a healthy microbiome seems like a possible elixir. Maybe that’s why so many are embracing radical concepts such as fecal transplants that use donor stool to repopulate good gut bacteria or even a synthetic microbiome made up of microbes grown in a lab.

The past year has brought developmental leaps in both methods, as science attempts to outpace the destruction of the microbiome, which has seen entire families of bacteria disappear from the guts of industrialized populations.

The U.S. Food and Drug Administration (FDA) has recently approved two different products for use with fecal microbiota transplant (FMT), a method by which healthy stool is transplanted into a recipient. One of the products is delivered directly to the colon via colonoscopy and the other is delivered in a pill form of stool intended to repopulate intestinal flora. The products are only approved for use with Clostridioides difficile (C. diff) infections.

A second approach—currently in the rodent research phase but with therapeutic intentions—is a synthetic microbiome of bacteria grown from scratch and mixed together in a design intended to mimic a human microbiome. While the treatment holds promise, there are some who question our ability to replicate this incredibly complex microbial community, one which we’re still trying to understand.

A Snapshot of the Science

Stanford University researchers have developed what they call “the most complex and well-defined synthetic microbiome” with more than 100 bacterial species that they then transplanted into mice. After two months, 98 percent of the flora colonized in the mice and remained stable. The results were published in September 2022 in the journal Cell. 

In fecal transplants, an entire microbiome is introduced into the human digestive tract. That makes it difficult to do research into what specific bacteria may be involved in certain diseases. The Stanford researchers say their synthetic microbiome research is aimed at creating a tool for the removal or modification of specific individual species. It would be the microbiome equivalent of gene silencing, an emerging area of science in which disease-causing genes are turned off.

“So much of what we know about biology, we wouldn’t know if it weren’t for the ability to manipulate complex biological systems piecewise,” said Michael Fischbach, corresponding author on the study and associate professor of bioengineering, microbiology, and immunology.

Microbiologist Kiran Krishnan told The Epoch Times that synthetic microbiomes will be beneficial for research, but he doesn’t think a whole human microbiome will be successfully replaced with a manmade version in his lifetime. Any attempt, he said, would likely end up like baby formula—a crude imitation that companies attempted to convince moms was better than breast milk—now associated with increased risks of obesity, allergies, and immune dysfunction.

“We cannot replicate what microbes do naturally. It’s too hard. There are mechanisms going on in the world of microbes that we don’t even understand from a biologist’s perspective,” Mr. Krishnan said. “Then you get into the whole world of quantum biology—microbes communicating in ways we don’t even know exist. Anytime we’ve thought we could outsmart nature, we’ve created problems.”

Fecal transplants, however, have taken off therapeutically with impressive results, particularly with C. diff infections that tend to recur and can drastically alter the quality of life.

Rebyota’s FDA approval in December 2022 was based on two studies in which 978 adults received at least one dose of donated human fecal matter. The success rate at eight weeks was 70.6 percent, compared to 57.5 percent in the placebo group, according to the FDA. Studies worldwide validate uniform FMT success for C. diff.

FMTs have been part of the standard of care for recurrent C. diff for years. Besides severe diarrhea, C. diff causes colitis, an inflammation of the colon. It affects about 500,000 Americans annually, commonly those taking antibiotics, which kill the good flora, leaving the immune system vulnerable to future infections. One in 11 people older than 65 with a health care-associated C. diff infection die within a month, according to the U.S. Centers for Disease Control and Prevention.

FMT Application Outside the Gut

Beyond C. diff infections, the FDA limits fecal transplants to clinical studies. Researchers are investigating FMT use with dozens of other infections, diseases, and conditions.

Gastroenterologist Dr. Thomas Borody is a pioneer in this field. He’s performed more than 35,000 microbial transplants at the Centre for Digestive Diseases Australia. There are almost no restrictions on its use in Australia. Dr. Borody holds more than 180 patents in areas such as FMT and the treatment of Helicobacter pylori, Crohn’s disease, and irritable bowel syndrome.

During a Malibu microbiome meeting several months ago, Dr. Borody presented case studies of success using transplants for constipation in conjunction with Parkinson’s disease. Not only did two patients experience relief from constipation, but tremors and other symptoms also vanished, Dr. Borody said.

“I took them to their neurologists to examine them and they said to me, ‘If you would have brought them to me now, I would have never diagnosed them with Parkinson’s disease,’” he said, though he noted that the two subjects were part of a trial of FMT on a dozen Parkinson’s patients. “Only two out of the 12 responded, which means there is a lot of work to do.”

Such miracle case studies are legendary online, where desperate patients search for alternatives to pharmaceuticals that don’t work well or have unpleasant side effects.

Proceeding With Caution

However, few doctors will offer FMTs outside FDA approval, except in rare situations in which patients have no other options and are informed of risks and benefits. That’s the guidance spelled out in a 2020 perspective article in Medicine in Microecology.

Most patients—and providers—view FMTs as natural, safe, and separate from conventional medicine, according to surveys reported in the article. In 2017, only 12 percent of those polled had knowledge of fecal transplants. Once informed, 77 percent said they would undergo the procedure if it was needed.

The procedure is often misunderstood and comes with a plethora of ethical and logistical ramifications. As awareness of FMTs grows, people with any number of conditions may consider it a possible remedy and pursue DIY transplants using stool from a healthy family member. Such tales are what motivated the Medicine in Microecology article, which highlights this concern.

“Finally, there is a need for clinicians to strive to educate and to persuade patients not to pursue FMT as a do-it-yourself procedure any more than they would perform an organ transplant or blood transfusion at home. The relative ease of the procedure does not cancel out its risks of harm. As such, upon encountering a patient who mentions considering a ‘DIY FMT,’ clinicians have an obligation to explain the real risks and to counsel against such a course of action,” the authors wrote.

Patient familiarity with the procedure already has many asking for it by name for conditions associated with dysbiosis. Dr. Ari Grinspan, associate professor of medicine and director of the fecal microbiota transplant program at Mount Sinai Hospital, told The Epoch Times he gets two to three requests a week.

Take, for example, the patient who asked for a fecal transplant after taking a drug called finasteride, known by the brand name Propecia, for hair loss that gave him sexual, neurological, physical, and mental adverse reactions. It’s such a common occurrence, it has a name—post-finasteride syndrome—and it’s associated with dysbiosis.

“I’ve seen this for all different kinds of things over the past couple of years,” Dr. Grinspan said. “It’s a common way that medicine fails, because we don’t have answers for everything.”

Many Unknowns of FMT

All the hype may be blinding some to the unknowns associated with FMTs, such as unintended changes in the microbiome that could lead to acute infections or chronic disease. Six patients contracted diarrhea-causing Escherichia coli infections after receiving donor stool for C. diff treatment in 2020. 

Other doctors have warned of the harm that could come from inadequately screened stool and unknown complications. The Medicine in Microecology article noted the need for record keeping on both short-term and long-term adverse reactions.

Given that many health care solutions are transactional—symptoms disappear quite possibly for the price of one or more side effects—researchers say it’s important to reserve fecal transplants for the most severe situations.

Root Cause Still Ignored

There’s another concern: An FMT does nothing to address poor choices, environmental exposures, and lifestyles that may have caused or contributed to dysbiosis in the first place.

Dr. Scott Doughty, integrative family practitioner with U.P. Holistic Medicine, told The Epoch Times that FMT has the potential to go the way of gastric bypass surgery, a weight-loss surgery that changes the size of the stomach to restrict the amount of food it can hold. A new anatomy forces habits to change, but it doesn’t make a patient eat less, crave healthier foods, or change the physiological root causes that might have led to obesity.

“I would hope the market for fecal transplant doesn’t skip over the notion that you got sick for a reason and let’s try to figure out what led to you getting sick so some changes can be made,” Dr. Doughty said.

Still, he remains excited and hopeful about the concept, which he said affirms the gut-focused work of holistic-minded physicians, including dietary changes, detoxification, lowering exposure to toxins, and addressing inflammation.

Why Dysbiosis Is a Growing Concern

It’s widely believed that industrialization has reduced microbiome diversity due to diet, herbicides, antibiotic usage, increased use of cesarean section and baby formula, over-sanitization, and reduced contact with soil and animals.

One very new discovery comes from a deep sequencing of the genomes from Hadza tribe stool samples collected a decade ago. New technology applied to the old samples allowed researchers to identify more species present in the microbiomes of one of the last remaining hunter-gatherer populations who live in Tanzania. They had an average of 730 species, compared to microbiome samples from California (277 species), Napali foragers (317), and Napali agrarians (436 species).

Published on July 6 in Cell, the study found that 124 gut-resident species have disappeared in industrialized populations. It also took a close look at the functional properties of those lacking species, which were predominantly in the fiber-fermenting genera Prevotella and the commensal Spirochaetota. Nonindustrial microbiomes were found to be more rich in bacteria associated with antioxidant and redox sensing functionality—roles of the microbiome that keep autoimmune issues at bay.

“The data generated from Hadza fecal samples in this study (collected in 2013–2014) may thus represent a critical permanent reference point for microbiome scientists to understand the impacts of industrialization on the gut microbiome,” according to the study.

The research found that Treponema succinifaciens—previously associated with a nonindustrialized lifestyle—is nearly completely absent from industrialized individuals. No Spirochaetota genomes were detected within Californian microbiomes.

A 2021 study published in BMC Microbiology validates the concern of our microbiome’s rapid change in industrialized settings, “particularly, the observed decrease of Spirochaetes and Prevotella in westernized communities.”

The authors note that these are likely linked to the rapid change in our lifestyles and dysbiotic microbiome, “which promote the etiology of chronic diseases.”