The human microbiome represents an expansive realm of both recognized and undiscovered microscopic entities, engaged in countless biochemical changes along metabolic pathways that remain uncharted.
A multitude of microorganisms, encompassing bacteria, viruses, and fungi, interact with human physiology, surpassing the count of human cells. Predominantly, these microorganisms are “beneficial,” contributing to the prevention of issues caused by disease-inducing pathogens. Although pathogenic microorganisms sporadically lead to acute ailments and contribute to chronic conditions.
However, occasionally even the harmonious inhabitants, termed commensal microorganisms, shift into detrimental proportions. Such imbalances, deemed dysbiosis, occur whenever the proportions are believed to be detrimental. Dysbiosis is presumed to drive inflammation and autoimmune disorders.
Research is swiftly documenting diverse microbial populations linked to conditions like autism spectrum disorder, Parkinson’s disease, Crohn’s Disease, Alzheimer’s disease, multiple cancers, cardiovascular disease, and others.
Given the escalating incidence of diseases, the notion of a wholesome microbiome presents itself as a potential remedy. This perhaps explains the embrace of innovative ideas such as fecal transplants, where donor stool reintroduces beneficial gut bacteria, or even a synthetic microbiome cultured in a laboratory.
The past year has witnessed notable progress in both approaches, as science strives to counteract the decline of the microbiome, which has witnessed the disappearance of entire bacterial families from the intestines of industrialized populations.
The U.S. Food and Drug Administration has recently sanctioned two distinct products for fecal microbiota transplant (FMT), a process involving the infusion of healthy stool into a recipient. In one variant, the transplant occurs directly into the colon via colonoscopy, while the other involves an ingestible form of stool meant to replenish intestinal flora. These products are solely sanctioned for use in cases of Clostridioides difficile (C. diff) infections.
A second method, currently at the experimental stage in rodent studies but with therapeutic aspirations, involves a synthetic microbiome crafted from scratch. This microbiome is a concoction of bacteria designed to imitate the complexity of a human microbiome. Although promising, there are concerns regarding our ability to replicate this intricate microbial community, which remains to be fully comprehended.
A Glimpse into the Scientific Landscape
Researchers at Stanford University have developed what they term as “the most intricate and well-defined synthetic microbiome,” featuring over 100 bacterial species. This synthetic microbiome was transplanted into mice, with 98 percent of the flora successfully colonizing and remaining stable after two months.
In the context of fecal transplants, an entire microbiome is introduced into the human digestive tract, making it challenging to pinpoint the specific bacteria implicated in particular diseases. The Stanford researchers’ work on synthetic microbiomes aims to create a tool for selectively removing or altering individual species. This concept parallels gene silencing, an emerging field where disease-related genes are deactivated.
While synthetic microbiomes could have research benefits, some researchers remain skeptical that a completely artificial version could effectively replace the entirety of the human microbiome within his lifetime. They liken such an endeavor to the situation with baby formula—an imperfect imitation that companies marketed as superior to breast milk, but is now linked to increased risks of obesity, allergies, and immune dysfunction.
Replicating the natural functions of microbes is exceedingly challenging due to the intricate mechanisms at play, many of which remain mysterious even to biologists. They also mentioned the realm of quantum biology, where microbes communicate in ways beyond current understanding. He cautioned against attempts to outsmart nature, citing historical instances where such efforts led to unintended issues.
In contrast, fecal transplants have gained therapeutic traction, especially for treating recurrent C. diff infections that can significantly impact quality of life. Rebyota’s FDA approval in December relied on studies involving 978 adults who received donated human fecal matter. At eight weeks, the success rate was 70.6 percent, compared to 57.5 percent for the placebo group.
Fecal microbiota transplants (FMTs) have long been employed to address recurrent C. diff infections, which cause colitis and affect around 500,000 Americans annually. C. diff often arises in individuals on antibiotics that disrupt beneficial flora, leaving the immune system vulnerable. FMTs offer hope beyond C. diff, with ongoing research exploring their application for various infections and diseases.
Despite online accounts of miraculous outcomes, FMTs are generally administered under FDA approval. Exceptions exist for rare cases with no alternatives, where patients are informed of risks and benefits. Public perception often sees FMTs as natural and safe, separate from conventional medicine.
As familiarity with FMTs grows, patients with different conditions may consider it as a remedy, potentially resorting to DIY transplants using healthy family member stool. This trend prompted a cautionary article in Medicine in Microecology, advocating for proper clinical guidance and discouraging self-administration of FMTs.
Uncharted Aspects of FMT
Amidst the fervor surrounding Fecal Microbiota Transplants (FMTs), certain uncertainties might be overlooked, particularly those tied to unintended shifts in the microbiome that could trigger acute infections or long-term ailments. In 2020, six patients developed diarrhea-inducing Escherichia coli infections after undergoing donor stool-based treatment for C. diff.
Other medical professionals have raised alarm over potential dangers arising from insufficiently screened donor stool and unforeseen complications. The Medicine in Microecology article underscored the importance of recording both short-term and long-term adverse reactions.
Given that numerous healthcare solutions exhibit a transactional nature—where symptoms recede at the possible cost of side effects—experts stress the necessity of reserving fecal transplants for the most severe cases.
Neglected Underlying Causes
Another concern lies in the fact that an FMT doesn’t tackle poor lifestyle choices, environmental exposures, and behaviors that could have triggered or contributed to dysbiosis in the first place.
FMT may be compared to gastric bypass surgery—a weight-loss procedure altering stomach size to restrict food intake. While it changes anatomy and habits, it doesn’t inherently modify dietary preferences, encourage healthier eating, or address the fundamental physiological factors that may have led to obesity.
Escalating Concerns about Dysbiosis
A widely accepted belief is that industrialization has diminished microbiome diversity due to factors such as dietary changes, herbicides, antibiotic usage, increased cesarean sections and reliance on baby formula, excessive sanitization, and reduced contact with soil and animals.
A groundbreaking finding stems from the deep sequencing of genomes from stool samples of the Hadza tribe, a hunter-gatherer community in Tanzania. By applying new technology to old samples, researchers identified a greater number of species in the microbiomes of this population compared to those of industrialized areas like California.
Published in Cell on July 6, the study disclosed that 124 gut-resident species have vanished in industrialized societies. It delved into the functional properties of these missing species, predominantly belonging to the fiber-fermenting groups Prevotella and the commensal Spirochaetota. Non-industrial microbiomes were found to contain more bacteria linked to antioxidant and redox sensing roles that help prevent autoimmune issues.
The study indicates that the data from Hadza samples could be a permanent reference point for understanding the impact of industrialization on the gut microbiome. Notably, Treponema succinifaciens, previously linked to non-industrialized lifestyles, was almost absent in industrialized individuals. Furthermore, no Spirochaetota genomes were identified in Californian microbiomes.
A 2021 study in BMC Microbiology supports concerns about the rapid transformation of our microbiome in industrialized environments. This shift, particularly the decline of Spirochaetes and Prevotella, is likely associated with changes in our lifestyles and dysbiotic microbiomes that contribute to the development of chronic diseases.