In early May, Merck & Co held the Human Microbiome Symposium, which saw academic experts presenting their newest results regarding understanding and possible utilisation of the gut microbiome to treat human disease.
The human microbiome represents the communal microorganisms populating the human gut. When in a healthy equilibrium with the host, these provide a symbiotic relationship. However, these gut organisms are also the prime suspects for a variety of diseases, though our knowledge about the exact impact these individual organisms have on our health is mostly still rudimentary.
Consequently, a main theme throughout the symposium was the need to provide evidence that demonstrates correlation and causation between individual bacterial species and human health, while also illuminating possible clinical targets.
An intriguing example was presented by Prof. Balskus from Harvard University. Despite the fact that around 50% of all genes found in the gut microbiome have yet to be annotated, her lab identified and structurally characterised specific enzyme choline trimethylamine-lyase (CutC), which is responsible for a bond cleavage using a glycyl radical enzyme mechanism.
This protein, and its corresponding metabolic pathway, represents an example for an ideal target for pharmaceutical products. Drugs targeting such unique enzymes could provide a scalpel-like tool in modifying the gut microbiome because these small molecules would target only a single species out of the possibly thousands of different species populating the human gut. Hence, such strain-specific compounds would represent a significant advantage over broadly active antibiotics, while also possibly minimising the problem of antibiotic resistance.
Another example was provided by Prof. Palm from Yale University, who also has a stake in Artizan Biosciences. While studying the impact the human immune system has on the gut microbiota, in particular of the specific antibodies immunoglobulin A (IgA), his group discovered a correlation between the extent of IgA coverage of gut microbiota and patient’s health. In addition, when gut bacteria from patients with inflammatory bowel disease (IBD) were purified based on the IgA coverage and implanted in germ-free mice, only IgA covered bacteria resulted in bloody stool. Since his lab also demonstrated that these IgA-covered bacteria can invade the gut mucosal layer, antibody coverage might represent a possible clinical target.
Despite limited understanding, the human gut microbiome will likely represent a significant target for novel drug development for the pharmaceutical industry. Currently available data strongly indicates that the correlation between bacteria and human diseases represents direct interaction between the microbiome and the host, which can possible be modified by future drugs. These novel treatment options might come as a full fecal transplant, as already known in the case of Clostridium difficile infections, by selectively introducing specific phyla or species into the patient’s gut, or by drugs directly targeting problematic strains.
In any case, modifying the human microbiome promises to be a powerful new tool that will hopefully soon be available to physicians.
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