The dynamic nature of the microbiome is driving momentum and enthusiasm for clinical research. There is evidence that microbial imbalance is a factor in an array of conditions and diseases, including inflammatory bowel disease (IBD), asthma, cancer, obesity, Type 2 diabetes, fatty liver disease, cardiac disease, women’s health, and neurological disorders. Recent advances in analyzing the microbiome and how it impacts immunity have put our ability to characterize and manipulate the microbiome within reach.
Investigations into the microbiome have ushered in a new area of opportunity for drug development in personalized medicine.
As some have said, the microbiome is the only “organ” that can be replaced without surgery. Consequently, multiple clinical studies are underway that are testing single commensals, mixtures of defined species and subspecies, and cocktails of microbiota-derived molecules targeting specific microbial species or pathways that are enriched or absent in the disease state in an effort to treat or prevent a variety of diseases.
The role of the human microbiome as an agent of health and a potential avenue for therapeutic intervention is rapidly evolving. The demonstration that fecal transplants are working in patients with C. difficile infection, and more recently in IBD, lends credence to the hypothesis that restoration of a healthy microbiome can influence disease outcomes. These successes of the investigations into the microbiome have ushered in a new area of opportunity for drug development in personalized medicine. Despite the current infatuation with the microbiome, arguably the science has not always lived up to the expectations. But the scientific foundation is gradually being constructed and many new studies are now forthcoming.
A Challenging Landscape
The microbiome is a complex and dynamic state affected by multiple influences. Not only do these influences increase the complexity of running a global study where the product under study is exposed to such inter-subject variability, there are major intra-individual variabilities that affect the microbiome. Changes in lifestyle, such as diet, age, socioeconomic status, and medication use, can lead to data reproducibility issues and statistically underpowered studies, where treatment groups run the risk of being significantly phenotypically, etiologically, and microbiologically different.
The diversity of the microbiome across individuals presents challenges for what defines a healthy or dysbiotic microbiome and how to select subjects who would be most likely to benefit from a microbial intervention. Clear and clinically meaningful human health endpoints that follow regulatory guidance will need to be used. There are also challenges in sample collection and extraction to enable clinical trial enrollment and to successfully achieve the endpoints.
While the challenges are great, the significant opportunity to impact health and well-being cannot be ignored. It is indeed an exciting new chapter in drug development.
Credit: Published in PharmaVoice September 2017