Next time you’re feeling lonely, think of the microbiome. Your body is host to an immense community of microorganisms, all of which help it operate. Among these, the gut microbiome is perhaps the most widely discussed. Intestinal microbiota play key roles in metabolic and nutritional balance, immunity, neuronal activity, and more. That’s why researchers have been focusing on the microbiome as a possible target for new therapies.
As noted in an article published in mSystems, advancements in fields like genome sequencing and gnotobiotics have further illustrated the microbiome’s intricate contributions to human health. As a result, researchers are testing interventions that could help modulate the microbiome and treat illnesses.
Which diseases could be treated or prevented with a microbiome-first approach? Human microbiome activity has been implicated in a broad range of chronic diseases and other conditions, including inflammatory bowel disease, diabetes, multiple sclerosis, autism, cancer, and AIDS, according to an article published by Labiotech. Research into the connection between the microbiome and these diseases is mounting. In 2018, there were more than 2,400 clinical trials conducted to test microbiome-related therapies, up from roughly 1,600 in 2017. According to an article published in Genetic Engineering & Biotechnology News in August of this year, more than 20,800 articles and studies in the field of microbiome therapeutics were published in 2020.
Currently, there is only one marketed microbiome-targeted therapy—fecal microbiota transplantation (FMT)—but FMT may soon be joined by a range of others. Here are some of the latest developments in microbiome therapeutics research, along with a breakdown of patient interest in these therapies and their market potential.
Fecal microbiota transplantation
As detailed in an article published in Nature in 2020, research into microbiome therapeutics was spurred by the US government’s $215 million Human Microbiome Project. Beginning in 2007, researchers used genome sequencing technologies to map out the compositions and mechanisms of our various microbiota communities. Eventually, experiments using rodents illustrated that microbial transplantation could affect myriad gastrointestinal, metabolic, and immunological disorders. This led to the development of FMT, which is currently the only FDA-approved microbiome-based intervention.
FMT, which is commonly used to treat Clostridium difficile (C. diff), involves the transfer of a sample of a microbial community from a healthy donor to an infected patient with the aim of replacing the disease-associated microbiome.
While effective in some patients, FMT does present some risks, including the possibility of negative interactions within the recipient’s existing microbiome, as well as the accidental transfer of pathobionts. In fact, the FDA issued a warning in March of last year after two patients died due to FMT treatments that used stool samples contaminated with E. coli.
However, the treatment works well enough that researchers are investigating whether FMT may treat other conditions.
More therapies on the horizon
There are several other therapies going through trials that are based on donor stool specimens. Last year, Seres Therapeutics reported that a phase 3 trial showed its C. diff treatment SER-109 reduced the risk of recurrent gastrointestinal infection by more than 30%. Likewise, Rebiotix reported that phase 3 trials demonstrated the efficacy of their microbial transplantation treatments. Finch Therapeutics’ phase 2 data, published in June, also revealed a statistically significant benefit.
Other conditions under examination include ulcerative colitis and Crohn’s disease, both of which are characterized by immunological dysfunction in the intestine. Researchers posit that the composition of the gut microbiome plays a major role in these forms of inflammatory bowel disease—that is, patients may have a lack of certain microbiota that keep inflammation under control.
These theories make sense when considering that the intestine is the body’s largest endocrine organ and immune organ. The intestine produces more than 30 hormones and is home to more than 70% of T cells. In fact, one group of researchers has identified a group of bacteria in the gut that can prompt the activity of cytotoxic CD8+ T cells, which can attack tumors. This research led to the development of a microorganism–drug combination that is currently in trials for the treatment of various cancers.
Studies are also illuminating potential treatment pathways in conditions that seem unrelated to the gut. For example, a study published in Nature in July 2019 found links between the gut microbiome of mice and the progression of amyotrophic lateral sclerosis (ALS). Researchers identified 11 microbial strains in ALS-prone mice that changed either as the disease progressed or prior to the mice developing ALS symptoms, according to a press release on the study. They also found one strain that appeared to significantly slow disease progression and prolong survival.
Another study, also published in Nature in 2019, found a relationship between upper-airway bacteria and the severity of asthma symptoms among children. Researchers found that the presence of bacteria like Staphylococcus, Streptococcus, and Moraxella in the upper airways was associated with asthma flare-ups. On the other hand, airways host to Corynebacterium and Dolosigranulum bacteria tended to be associated with periods where asthma is well-controlled.
While these studies are preliminary, researchers are hopeful that their findings could lead to interventions that positively alter microbiomes.
Public awareness and market growth
Patient awareness and investor interest in microbiome therapeutics are growing. An October 2020 survey found that while 75% of respondents consider the microbiome to primarily affect digestive and gut health, roughly half expressed an interest in how microbiota affect immunity, and approximately two-thirds of respondents said they use some kind of microbiome-related product. If these trends hold, patients may start asking their physicians questions about how microbiome therapeutics work and what evidence exists to support their use.
The microbiome buzz has caught on among some of the larger pharmaceutical companies, too. In recent years, DuPont, Merck, Pfizer, Boehringer, Takeda, Gilead, and Novozymes have all made investments in developing some kind of microbiome-related product. According to an article published by Biospace in 2020, the total amount of investment in microbiome research companies since 2014 is estimated to exceed $5 billion, and investors include big healthcare philanthropists like Bill Gates.
Microbiome therapeutics still have a long way to go before reaching the market, but if the early research is any indicator, we’re only scratching the surface of what’s possible in the field.
Read more about the gut microbiome on MDLinx: