Mine vs. Yours: Can Understanding the Microbiome Improve the Efficacy of Biologics?
It seems the Earth’s surface and all of its organisms—from the darkest recesses of the ocean floor to sulfuric vents and human bowels—are filled with bacteria. But only recently has the existence and composition of human gut bacteria, or gut microbiota, piqued the interests of scientists, pharmaceutical startups and physicians alike1 because of mounting evidence that gut microbiota is intricately linked to our health. Estimates suggest that bacterial cells in the human body outnumber human cells 10 to 1 and play an important role in a number of autoimmune diseases including “diabetes, rheumatoid arthritis, muscular dystrophy, multiple sclerosis, fibromyalgia and some cancers,”2, as well as metabolic diseases such as obesity.3 Most intriguingly, an individual’s diet can play an essential role in the composition of gut microbiota, which in turn affects their health and propensity to develop the abovementioned diseases.4
Mixing Oil and Water? Microbiome and Biologics Relationships
Recently, scientists have discovered that the gut microbiome can influence drug metabolism and the efficacy of drug therapies5, information that is essential for understanding the metabolism of biologics. Biologics are often administered by intravenous injection, but diffuse from the vascular space into interstitial tissue space and from there, enter the lymphatic system.6 As biologics travel to their therapeutic targets, they encounter small molecules produced by the human microbiota7, such as lantibiotics and microcins, that may affect the binding properties of these biologics or even their abilities to identify receptors on their target organs. As discussed above, individuals have different compositions of microbiota, which may differentially affect their responses to biologics therapies.
In general, studies that elucidate the underlying mechanisms for the “absorption, distribution, metabolism, and excretion (ADME) of biologics” have not been thoroughly conducted.8 But as biologics become a greater component of the portfolios of pharmaceutical companies, the industry has begun to focus on the importance of ADME studies for the success of biologics. To take this effort one step further, industry researchers should also seek to understand how highly synthesized small molecules from human microbiomes can similarly influence the success of biologics and their usefulness as therapeutic agents in certain populations.
Removing Roadblocks and Setting Up for Success with Biologics
For companies interested in creating better biologics inspired by gut microbiome research, their efforts must take two forms: 1) the development of methods for testing the activity of biologics in different microbial contexts and 2) the development of novel biologics. But in order to remove barriers to innovation and develop these two components, biologics companies must necessarily optimize lab efficiency through the use of digital solutions, which can lead to progress at various stages of product design:
Project initiation: In identifying alternative biologics, characterizing their ADME profiles and determining how these profiles (and the biologics themselves) change in specific microbial contexts, novel experiments need to be designed. If research team members are able to review and collaborate in real-time, the process of tracking and identifying promising projects can proceed more quickly.
Design: To design the appropriate experiments, past experiments should be studied. For example, has the organization previously identified any metabolic changes after administering biologics? If so, digital solutions enable project members to easily retrieve that information while collecting literature analyses in a single location in order to more quickly move from project idea to experimental design.
Materials: Digital solutions also enable researchers to determine the materials on site and those that must be ordered, again enabling project members to more efficiently use their time and implement their ideas.
Experiments: Important experiments can be conducted with direct, real-time input from other team members. For example, to develop novel biologics, one might first determine how different small molecules released by the gut microbiome affect the metabolism of biologics. Do the molecules obscure the binding site of a class of biologics to their target receptor? Do they change its excretion or alter aspects of its function via glycosylation? This information can then be used to inform how other biologics inspired by the test sample, could be made to resist negative changes. In this case, BIOVIA Biologics Solution facilitates the use of bioinformatics for early discovery and analytics for sequence annotation and data modeling technology that can assist in the development of new biologics.
Analysis: Managing, tracking, processing and understanding the experiments is facilitated by both data modeling technology and bioinformatics capabilities as well as the ability to share data and collaborate with other team members.
Software suites like BIOVIA Biologics Solution enable research and development companies to accelerate novel biologics to market, while the ability to create biologics based on information about the gut microbiota can significantly improve drug efficacy and, ultimately, a brand’s reputation for excellence. To determine how BIOVIA Biologics Solution can improve efficiency and promote product innovation at your company, please contact us today.
- “Nature Special: Human Microbiota,” http://www.nature.com/nature/focus/humanmicrobiota/ ↩
- “Microbiome Therapies,” http://www.techcastglobal.com/home/-/asset_publisher/icgQEJnCo7Dy/content/microbiome-therapies/maximized;jsessionid=D33B9A43914E3BE82CFEE4D2C8B471C1 ↩
- “A core gut microbiome in obese and lean twins,” January 22, 2009,
- “Gut microbiota composition correlates with diet and health in the elderly,” August 9, 2012, http://www.nature.com/nature/journal/v488/n7410/full/nature11319.html ↩
- “Drug metabolism: manipulating the microbiome,” March 27, 2015, http://www.pharmaceutical-journal.com/news-and-analysis/features/drug-metabolism-manipulating-the-microbiome/20068240.article ↩
- “PK/PD of Biologics,” http://bit.ly/1Po5bEw ↩
- “Small molecules from the human microbiota,” July 24, 2015, http://www.sciencemag.org/content/349/6246/1254766.abstract ↩
- “Challenges and Opportunities in Absorption, Distribution, Metabolism, and Excretion Studies of Therapeutic Biologics,” December 2012, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475845/ ↩