June 29, 2023 – Curtis Huttenhower, professor of computational biology and bioinformatics at Harvard T.H. Chan School of Public Health, studies the role that the microbiome plays in health and disease. He most often focuses on the human gut, but recently his research has expanded into pets, including dogs and cats.
Q: What motivated you to study the gut microbiome of pets, and how does it relate to human health?
A: I was initially excited about the chance to extend our human microbiome research into pets because I’ve been a cat dad for decades, and companion animal well-being is one of my biggest personal passions. As we got a few studies off the ground, though, I came to realize how many scientific opportunities there really are in companion animal microbiome research, both for our furry friends’ sake and for our own.
First, everyone wants their pets to live forever, and our studies about their gut microbiomes have the potential to improve animal health in a variety of ways. For example, chronic kidney disease is one of the most common diseases of old age in cats. Since the microbiome can be a significant source of kidney-damaging uremic toxins, we hope to be able to avoid that risk factor with appropriately targeted diets. Additionally, the research community has learned a lot over the past few years about manipulating the human gut microbiome—discoveries that can be applied to promoting animal health. For instance, the success of certain types of cancer treatment depends on the gut microbiome, as does recovery from antibiotics, which interfere with beneficial microbes in addition to pathogens. Furthermore, the addition of the right beneficial microbes can improve management of conditions such as inflammatory bowel disease.
Second, some aspects of pets’ lifestyles make their gut microbiomes intrinsically easier to study compared to those in people. Many pets eat monotonous, chemically controlled diets, so we can measure very precise interactions between long-term dietary exposures and microbial responses. In contrast, humans rarely eat exactly the same thing twice, let alone the same perfectly controlled meal day after day. If we can use pet diets to understand how specific dietary components interact with their gut microbes to promote or prevent obesity, we can leverage that information for human health as well.
Q: You’re collaborating with Hill’s Pet Nutrition, a pet food company. Can you talk about the work you’re doing together?
A: Hill’s runs a Pet Nutrition Center with a unique setup that enables them to refine nutrient levels in their products and accommodate very sophisticated microbiome research. At the center, roughly 450 dogs and 450 cats receive top-notch attention from technicians who are dedicated enough to know each animal’s name and personality. The center has on-site medical care and food manufacturing, as well as a custom-built robotic system that automatically tracks the specific types and amounts of food consumed by each individual animal. The composition of each food is known when it’s manufactured, and when it comes out the other end—so to speak —stool samples can be collected nearly immediately, processed, frozen using an extremely well-validated protocol, and assayed on site for microbial DNA, metabolites, and more. Needless to say, that level of detail is impossible with human studies.
With experts at Hill’s, we’re working on a whole series of human and pet studies that investigate the interactions between diet and microbiome. In one study that we’ve completed, we investigated dogs that consumed foods with 12 different dietary fiber sources and compositions—for example, high- vs. low-fiber, or corn starch vs. pea fiber. One of the most surprising results was that, despite the completely controlled diets and uniform living environment, differences in gut microbes among dogs still resulted in very distinct chemicals being produced via microbial fermentation during digestion. Some dogs could ferment the same fiber more efficiently than another, just because of different microbes that happened to have taken up residence in their guts.
These differences in gut microbial chemistry may help to explain some aspects of weight maintenance and healthy aging in both dogs and humans, since the same microbial “personalization” exists in people too. Most microbial fermentation products are good, generally speaking, and thus more efficient fermentation is likely beneficial. Our results also agree with several human diet studies we’ve published, which found that the degree to which high-fiber diets help prevent inflammation is dependent on which gut microbes people have. Similarly, we’ve found that how much a Mediterranean diet improves heart health is dependent on which gut microbes are present.
Our diet studies expose a theme that’s become important in recent microbiome research: Microbes are just little bags of chemistry, and they can perform a really remarkable range of metabolism. This helps to explain why different people respond differently to the same diets, or why the same drug might work better in one person than in another. We all carry vastly different bugs in our microbiomes—far greater variation than among animals in a shared environment—and those microbial differences mean that the types of chemistry going on throughout our bodies can change subtly from person to person. Figuring out exactly how microbes contribute to that chemistry can help to improve drug dosing, personalized therapies, and healthy eating guidelines.
Q: What are the broader public health implications of your work?
A: The connections between pet and human health reflect the One Health initiative advanced by the WHO, CDC, and other public health organizations, which focuses on the concept that human, animal, and environmental health are all inextricably interrelated. For example, epidemiological studies have shown that infants exposed to more furry pets and green space early in life have a lower risk of immune and allergic conditions later. We’ve come to understand that some of those effects are due to the microbiome—acquiring the “right” microbes at the “right” times leads to better lifelong health. However, the opposite can also be true. Due to greater use of antibiotics in veterinary medicine than in human medicine, microbes in a pet’s gut can become antibiotic resistant. If such resistant microbes, or their genetic material, transfer to an owner, they could eventually pose a health risk.
Relatedly, we’re working on another study in collaboration with the Nurses’ Health Study 3 and Growing Up Today Study, which are run by Harvard Chan School and the Channing Division of Network Medicine at Brigham and Women’s Hospital. We’re comparing microbiomes from both pets and their owners, with the goal of understanding which microbes can transfer between the two, how, and what the consequences on immune or metabolic health might be. It will be exciting to discover how this new line of research turns out, for the sake of both human and animal health.
– Jay Lau