The microbiome and germ-free mice as drug development tools, and AI’s influence on preclinical imaging
Earlier this year, Eureka produced a video story, featuring Charles River scientist Ken Henderson, which described how the microbiomes of germ-free mice are monitored. Germ-free mice are a valuable tool for companies developing microbiome-based therapeutics. It is the role of lab facilities, like the one Henderson is part of, to ensure that the germ-free mice remain germ-free. This week Henderson, who is the Senior Director of Laboratory Scientific Diagnostic Services, authored a piece for Pharmaceutical Outsourcing, suggesting that when testing new drug compounds in mice—the preferred animal model in most preclinical animal studies—a healthy gut microbiome is an often overlooked factor in determining drug response. In fact, therapeutic response can be directly linked to the health of the gut microbiome, Henderson says.
One obvious solution might be to develop and stabilize standard microbiomes. Unfortunately, biology is messy and establishing static microbiomes are confronted with many different outside forces that the animals interact with, including food, water treatment, bedding material, method of birth and housing. How mice are shipped can also cause microbiome drift.
Building a customized microbiome tailored for a particular study is also a challenge, says Henderson. Germ-free mice are the preferred option as long as they can be colonized. An alternative to germ-free mice is to use antibiotics to clear the path for a new gut microbiome. “As the influence of the microbiome on research becomes more recognized, lab animal vivariums will need to work with researchers to identify the best means to provide and maintain research models that meet their needs,” concluded Henderson. “Researchers will need to determine their need for a stable and consistent gut microbiome and potential advantages of this additional variable to consider in their development of a research model.”
Keeping with the topic of the microbiome, PharmaVoice published an article this month that focused on the burgeoning research being done around microbiome-based therapeutics. Their article also featured important perspectives from Henderson, who noted that Charles River has seen an increase in proposals for studies related to the microbiome and live flora. Inflammatory bowel disease is a popular area of research. “There’s been great progress in understanding which bacteria increase or decrease in individuals who have inflammatory bowel disease, as well as what phage diversity might be present”, he said.
Artem Shatillo, head of MRI at Charles River’s neuroscience drug discover site in Kuopio Finland, was quoted in Biocompare’s article on how AI is advancing the field of preclinical imaging. Shatillo described a stroke study that uses deep learning to teach a network algorithm to detect borders of ischemic areas in rat models. “Software tools like this are dramatically accelerating data analysis, while also increasing consistency and quality of the outcome compared to manual segmentation,” said Shatillo. “In turn, this can make a difference between ‘go’ and ‘no go’ decisions for the drug candidate.”