The human body hosts a complex ecosystem of microorganisms known as the microbiome. These communities of bacteria, viruses, and fungi inhabit sites like the gut, skin, and lungs, participating in various physiological processes. A new class of treatments, microbiome-based therapeutics, seeks to treat diseases by modulating these microbial communities. This approach views microbes as potential tools for maintaining health and treating disease.
Mechanisms of Action
One mechanism is competitive exclusion, where beneficial microbes introduced into the gut can outcompete pathogenic organisms for nutrients and attachment sites on the intestinal lining. This process limits the ability of harmful bacteria to establish a foothold and proliferate, preventing infections.
These therapies also modulate the host’s immune system, as the gut microbiome plays a role in training and maintaining immune balance. Microbiome-based treatments can help restore this by promoting the development of regulatory T cells. These specialized immune cells suppress excessive inflammation, creating a more tolerant immune environment for inflammatory and autoimmune conditions.
The metabolic activity of the microbiome is another source of therapeutic action. Gut microbes ferment dietary fibers indigestible by the host, producing beneficial compounds known as metabolites. Short-chain fatty acids (SCFAs) like butyrate, propionate, and acetate serve as an energy source for colon cells, strengthen the gut barrier, and influence processes throughout the body.
Types of Microbiome Therapies
Fecal Microbiota Transplantation (FMT)
Fecal Microbiota Transplantation (FMT) is a procedure involving the transfer of fecal matter from a healthy donor to a recipient to restore a healthy microbial community. The principle is to introduce a complete ecosystem of microorganisms to repopulate a disrupted gut.
The primary use of FMT is for treating recurrent Clostridioides difficile infection (rCDI), where it has success rates as high as 90%. Donors are carefully screened to prevent transmitting infectious agents. The material is minimally processed before administration via colonoscopy, enema, or oral capsules.
Live Biotherapeutic Products (LBPs)
Live Biotherapeutic Products (LBPs) are a more refined approach to microbiome therapy. LBPs are biological products containing live organisms, such as bacteria, intended for the prevention or treatment of a disease. Unlike FMT’s transfer of a whole microbial community, LBPs consist of specific, well-characterized strains of bacteria as single agents or in selected consortia.
This targeted approach offers greater consistency, controlled dosing, and a more predictable safety profile. LBPs are developed through rigorous trials to establish their efficacy, distinguishing them from over-the-counter probiotics sold as dietary supplements. This allows for selecting bacterial strains with known therapeutic mechanisms, like producing specific metabolites or modulating immune responses.
Microbiome Modulators
Microbiome modulators are therapies designed to alter the existing microbiome rather than introducing new organisms. Prebiotics are selectively used by host microorganisms, promoting their growth and activity; these are often dietary fibers like inulin. Postbiotics consist of the beneficial compounds produced by microbes, such as SCFAs, which are delivered directly.
Phage therapy uses bacteriophages, viruses that specifically infect and eliminate targeted bacteria. This method can remove pathogenic bacteria from the gut without harming the beneficial members of the microbial community.
Therapeutic Applications and Targeted Diseases
The most established application for microbiome-based therapeutics is treating recurrent Clostridioides difficile infection (rCDI). This infection often occurs after antibiotic treatment depletes protective gut bacteria, allowing C. difficile to flourish. The pathogen releases toxins that cause severe diarrhea and inflammation.
Fecal microbiota transplantation has proven highly effective in breaking the cycle of recurrence by reintroducing a diverse microbial community that can suppress the pathogen. The FDA has approved microbiome-based products specifically for this indication.
Beyond C. difficile, these therapies are being investigated for inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis. IBD is associated with an imbalance in the gut microbiota, and the goal is to restore a balanced community to reduce inflammation. While results from clinical trials have been mixed, research is ongoing to identify the most effective microbial compositions and treatment protocols.
The microbiome also plays a role in cancer immunotherapy, as studies show the composition of a patient’s gut microbiome can influence their response to treatments like immune checkpoint inhibitors. Certain gut bacteria can enhance the body’s immune response against tumors. Clinical trials are exploring whether modulating the microbiome can make these cancer treatments more effective for more patients.
The potential of microbiome therapies extends to metabolic disorders, as research has linked gut microbiota imbalances to conditions like obesity and type 2 diabetes. Studies are underway to determine if altering the microbiome can improve metabolic health. These investigations explore how microbial products, such as short-chain fatty acids, influence glucose metabolism and appetite regulation.
Regulatory Landscape and Development Challenges
Bringing microbiome-based therapeutics to market involves navigating a complex regulatory landscape. Regulatory bodies like the U.S. Food and Drug Administration (FDA) oversee the development and approval of these novel treatments. Depending on their composition and intended use, these products may be classified as drugs, biologics, or medical devices, each with its own regulatory pathway.
A challenge in the development of microbiome therapies is ensuring manufacturing consistency. For LBPs, which are composed of specific bacterial strains, the challenge lies in producing a stable and pure product. Every dose must contain a consistent number of viable organisms, requiring strict adherence to Good Manufacturing Practices (GMP).
The complexity and variability of the human microbiome present another hurdle, as each individual has a unique microbial community influenced by diet, genetics, and environment. A microbiome-based therapy may not have the same effect in every person. Research is focused on predicting how a therapeutic will interact with a patient’s existing microbiome to develop personalized treatments.