It wasn’t until the 1980s’ when modern techniques in molecular biology – most notably PCR and DNA sequencing – enabled scientists to get a deeper, fuller understanding of microbial communities. These advances led to the discovery of a number of potentially health-promoting novel strains whose functions are yet to be fully understood.
Modern microbiome therapies
The history of the application of bacteria in medicine has shaped the way people think about novel microbiome-derived products. Having in mind FMT and probiotic models, we could observe two distinct, yet overlapping paths.
The first one, following a top-down development approach, relied on the observed beneficial effect of fecal bacteria transplantation. The key idea behind the process is to understand the transplanted material and to narrow down the consortium.
A number of players in the microbiome industry follow this product development scenario. Some key companies like Seres Therapeutics, Rebiotix or MaaT Pharma are achieving successes by developing their products with full fecal consortia as a starting point.
The fundamental advantage of this approach is that it significantly accelerates the research. Starting with an already working product – FMT – you can incrementally add the value by refining the consortium that the product is made of. What is more, when developing a novel product, using FMT in an initial phase of R&D allows to quickly and cost-effectively evaluate the applicability of microbiome-derived intervention.
On the other hand, it must be underlined that the microbiome is an extremely complex ecosystem. It takes a lot of research (and a large budget!) to fully understand the relationships between numerous strains in the community. After an initially successful development of basic products, it requires much effort to transform the FMT into a well-understood, fully controlled therapeutic with a described mode of action (MoA).
Alternatively, another approach for the utilisation of the gut microbiome’s potential in therapeutics has been developed. With the bottom-up approach, companies like Enterome, Senda Biosciences or 4D Pharma are leveraging the very specific mechanisms identified in the microbial samples. These companies spent a significant amount of time upfront to identify the potentially key activity of the microbiome and then develop a product based on that information.
Within this approach, we can distinguish two main modalities investigated by researchers. The first one relies on identified immunostimulatory molecules present in or produced by bacteria. This is the key path for companies such as Enterome and Everimmune. To reach this point, it is crucial to understand both the human immune system and the gut microbiome. Another strategy is to utilize bacterial metabolites (postbiotics) that are identified as effectors. This is what SFA Therapeutics, Axial Therapeutics and Kaleido Biosciences aim for. Moreover, a number of ventures exploit those mechanisms indirectly by altering the bacterial growth conditions with pro- or antibiotics.
