The Galien Forum USA 2018

The Gut Microbiome: Opportunities and Challenges

The gut microbiome is formally defined as the genomes of the microbes that live inside the gut. It is a complex, interactive, multispecies microbial community composed of bacteria, fungi, archaea, and viruses. While the vast majority of the gut microbiome is composed of just 30-40 bacterial species, there more than 1,000 in total, containing about 100x the number of genes as can be found in the human genome.

In the past decade, there has been an exponential increase in research focused on the gut microbiome, owing largely to advances in technologies, including high-throughput sequencing, proteomics, and metabolomics, that have enabled characterization of microbial communities in healthy and disease states. This work has been facilitated by large-scale endeavors such as the Human Microbiome Project, which was launched in 2007.

The findings to date indicate that gut microbiomes are remarkably diverse among individuals, varying by sex, age, diet, and geography, just to name a few. Moreover, this system has been implicated in a broad array of physiology, including immune system development and homeostasis, regulation of intestinal endocrine functions, bone density, synthesis of vitamins, and gut-brain signaling. Links to a number of diseases, including gastrointestinal, respiratory, cardio-metabolic, autoimmune, oncology, and central nervous system disorders have also been established, although there are limitations to many of these studies and much more work is needed to establish causality and the mechanistic basis for the findings.

Despite the early stage of microbiome research, the exciting and provocative findings to date have triggered enormous interest and investment in translational programs in the biopharmaceutical industry. Currently there are more than 50 companies dedicated to the field, spanning all of the potentially relevant therapeutic areas and focusing on therapeutics, diagnostics, and even direct-to-consumer microbiome sequencing. The companies include small seed-stage firms, venture-backed private companies, and a handful of publicly-listed entities. They have raised hundreds of millions of dollars to finance their research efforts, the most advanced of which includes multiple late-stage clinical studies seeking to replicate fecal transplant therapies for C. difficile infections. A number of large pharmaceutical companies have also made a significant push in the field, via both equity investments and collaborations, including Johnson & Johnson, Takeda, Roche/Genentech, Allergan, AbbVie, BMS, and Nestle Health Sciences. Such an investment is sure to provide a better understand of the role of the microbiome in health and disease, and will hopefully have a broad impact on human health, although it is too early to know how long it will take to realize the full translational potential of these efforts.

This Panel Forum will discuss opportunities and challenges associated with gut microbiome research and translation. The current state of understanding of this complex system in physiology and disease will be discussed, and participants will provide a candid assessment of the potential for translation in the near term and beyond. This Panel will be chaired by Nancy Thornberry, CEO of Kallyope, who had the privilege of accepting the Prix Galien USA award for Best Pharmaceutical Agent for Januvia on behalf of Merck in 2007, and who is currently working to advance translational research on the gut-brain axis.