The premise behind microbiome-based therapeutics is straightforward: identify differences in the microbiome of people suffering from a particular disease, and then try to make the sick person’s microbiome more like the healthy person’s.

Rankings from the most radical (or just plain stomach-turning) to the most standard, here is a snapshot of microbiome-based therapeutics:

Fecal transplants represent the blunt approach of entirely resetting a patient’s microbiome with a presumably healthy one. There are a few companies trying to standardize this approach, including CIPAC (Laguna Beach, CA), and Rebiotix (Roseville, MN). Both companies are working to develop standardized, pre-screened fecal matter as a therapeutic for C. difficiles infection—unfriendly bacteria that cause severe diarrhea, affecting several million people annually and leading to thousands of deaths.

Most people harbor low levels of C. difficiles without a problem. The use of antibiotics, however, can wipe out the friendly bacteria that keep C. difficiles in check. The current standard of care is treatment with vancomycin—an antibiotic that many strains of C. difficiles are becoming resistant to. Resetting the microbiome may be a safer and more effective approach for the long term.

Other companies are working on a more targeted approach: defining and introducing groups of specific bacterial strains (a consortia) likely to be beneficial in a particular disease state. This approach enables greater specificity and quality control. Vedanta Biosciences (Boston, MA) exemplifies this approach in their identification of bacterial strains that have been shown to suppress inflammation and are decreased or missing in patients with chronic gut inflammation.

An even more targeted approach is to isolate a protein or small molecule being secreted by a strain of bacteria that gives it its therapeutic effect, and develop only that molecule as the therapeutic. GT Biologics (Aberdeen, United Kingdom) has taken this approach in developing a Crohn’s disease treatment based on an anti-inflammatory protein originating from Bacteroides thetaiotaomicron. Although this approach may be more in line with familiar development and approval pathways, in some cases these products may not be sufficient in treating microbiome-associated diseases, since drugs produced in this way will lack the ability to colonize the intestinal tract as an actual bacterium would. Further, there may be important and undefined interactions happening between different communities of bacteria that a single protein will not be able to replicate.


We have heard the commercial, “Activia helps regulate the digestive system when consumed daily for two weeks as part of a balanced diet and healthy lifestyle.” Activia and food products marketed as “probiotics” are sold at a premium because they claim to promote the growth of friendly bacteria. While these products certainly cannot hurt and may be an important part of a healthy diet, they are simply not potent enough to benefit individuals who are sick from microbiome imbalance.


Every surface and crevice of your body is teeming with microbes. Think about that buffet you had for lunch—how many of those microbes from the person in front of you fell into the very same dish you took your scoop of food from?

Your respiratory and gastrointestinal tracts have also been been colonized, playing host to thousands of different species. Did that buffet line include any sneezers?

In fact, bacterial cells in our body outnumber human cells by about ten to one. Bacteria alone contribute a few pounds of weights for every 100 pounds of human. Yet most of us go about our daily lives with no awareness of these invisible passengers, much less an appreciation of their vital interactions with our own cells.

Until recently, scientists (like those of us in the buffet line) have also been guilty of ignoring this bacterial community.

Medicine has largely been concerned with the very small percentage of bacteria that cause diseases such as pneumonia. That paradigm is changing quickly. On an almost weekly basis, new findings inform us of these microorganisms’ role in regulating the healthy functioning of important processes such as digestion and immunity, and their role in keeping disease-causing bacteria in check.

Imbalances within the microbiome have been linked to a range of disorders including obesity, inflammatory bowel disease, type 2 diabetes, anxiety, and depression.

What does this mean for biopharma? In this issue, we explore some early stage approaches to translating our growing knowledge of the microbiome into mainstream clinical treatments and diagnostics.


The differences in microbiomes between healthy and sick people are being used as diagnostic biomarkers. As data on the specific genomic signatures of the microbiome become better characterized, companies such as Enterome (Paris, France) and Metabogen (Gothenberg, Sweden) are developing diagnostics based on detecting these differences.


The human microbiome is the aggregate of microorganisms (bacteria and fungi) that reside on the surface and in deep layers of skin, in the saliva and oral mucosa, on the surface of the eye, and in the gastrointestinal tracts.

Characterizing the microbiome is done in part through metagenomics, or the study of genetic material recovered directly from samples as opposed to grown in the lab.

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