The microbiome may sound like a futuristic concept, but in reality, it is very much amongst the most promising frontiers in veterinary and human medicine. More importantly, it’s happening now. What exactly is the microbiome? It's surprisingly simple and utterly complex all at the same time. To start, each region of the body — whether that be equine or human — has its own microbiome, however, the gastrointestinal microbiome is where veterinarians, medical doctors and researchers are placing their bets. One such researcher is Dr. Diana Hassel of Colorado State University’s Veterinary Teaching Hospital. A surgeon and high-level triathlete in her own right, Dr. Hassel is breaking new ground in her work surrounding the microbiome and its effect on not only equine health but human health as well. She explains, “the GI microbiome is the combination of all of the microbes that reside in one’s gastrointestinal tract. Those consist of bacteria, fungi (yeast), protozoa, viruses and archaea. Our microbes outnumber the cells in our body by a factor of about 10 to 1. Even more impressive is that mammalian cells express about 20,000 genes, but there are 2-20 million genes expressed in the microbial population of the gut.”
Research into the microbiome, its structure and potential impact on both equine and human health is moving rapidly while currently in its infancy. There’s so much to know in this potential game-changing arena, and big plans are being made for the studies that will bring key answers to questions that could reshape the face of medicine. “We are in the early stages of understanding the role of the microbiota in health and disease,” says Dr. Noah Cohen, Associate Department Head for Research and Graduate Studies and Professor of Large Animal Internal Medicine at Texas A&M’s College of Veterinary Medicine. “In a sense, we don’t know much, and on the other hand, we know a lot,” he says. “What we know is that the microbiota can influence metabolism, exclude pathogenic bacteria that cause disease, alter behavior, impact development of immune responses and more.” Dr. Cohen’s colleague at Texas A&M, Assistant Professor of Large Animal Surgery, Dr. Canaan Whitfield, adds, “what we know is that the microbiome has a profound impact on the host,” referring to the health of the horse. “The findings on the human side have linked microbiome alterations with a huge number of seemingly unrelated diseases like autism, diabetes, heart disease, obesity and many gastrointestinal diseases like inflammatory bowel disease. While the equine research lags behind the human field, equine fecal microbiome alterations have been linked to colic, colitis and laminitis. Many groups are quickly working to link microbiome alterations to several other diseases. We know the microbiome is important to horse health, we just don’t know how the microbiome regulates host health nor have we nailed down the exact alterations of the horse’s microbiome that may lead to disease.” There’s a tremendous amount of discovery to come, and the veterinary community looks to the microbiome with excitement for its potential in both preventing and treating disease.
The exact function and impact of the microbiome may remain a bit of a mystery, but one component that researchers are eyeing closely is the equine metabolome. “The GI metabolome is the complete set of small molecules in the gut that reflects the interaction between an organism’s genome and its environment,” says Dr. Hassel. “It’s likely that the metabolomic changes — from both bacterial population changes and changes in bacterial gene expression — play an important role in altering health.” Dr. Whitfield expounds on the metabolome, adding “a few leading theories are that there are microbiota-derived metabolites — metabolites produced by the microbiota — that interact with the host to mediate a beneficial effect.” Quite simply, loss of these metabolites can lead to disease in the horse. One such instance of cause and effect being investigated is the use of antibiotics, non-steroidal anti-inflammatories and other common medications that are being shown to alter the microbiome and potentially disrupt its balance. While there is an important place for these medications in veterinary medicine, researchers hope that with further study, they can recommend better protocols for when to use these drugs and how to counteract their side effects.
With a large percentage of the immune system residing in the gut, the health of the microbiome is thought to play a significant role in a horse’s ability to ward off illness and remain well. A healthy, diverse and properly-functioning gut sets the stage for a strong immune system and a healthier animal. “Another mechanism by which the microbiome influences health is by interacting with host immune cells,” says Dr. Whitfield. “The wall of the gastrointestinal tract is rich with immune cells. These cells contain binding sites, called pattern recognition receptors, that recognize various molecules on bacteria in the gut microbiota. When these receptors bind to these molecules, they can induce signal transduction that results in many different outcomes depending on how many and which types of molecules or receptors were engaged. The subsequent actions can be as diverse as improving intestinal barrier function, to inducing immune cells to be more tolerant of bacteria — i.e. less inflammatory,” he says. These are two examples amongst many that show how the microbiome can influence the health of the horse and, in particular, the immune system.
Perhaps one of the greatest advantages to equine and human research alike is that the horse is often an excellent model for the human and vice versa. Several areas of equine medicine are able to emulate human medicine, with the same being true for human doctors looking to capitalize on the often much more rapid progress that equine veterinarians and researchers are able to make. “While there are marked differences between horses and humans,” says Dr. Cohen, “what we learn in horses could help humans.” Dr. Whitfield agrees, “there are clear areas of cross-over in both directions. Obviously, research in this area on the human side is outpacing the equine side, but I think we can use those findings and approaches to gain information about horses. The other direction could also be true in that many of the same diseases that affect people affect horses, and by studying horses, we can learn valuable information about human disease.” By studying the microbiome in horses, it allows veterinarians to gain significant knowledge from larger sample groups with greater ease. Horses are simply easier to work with than humans, and compliance can be strictly monitored. “Using the horse, we can conduct studies that would be difficult in people; diet change for example,” says Dr. Whitfield. “Many people struggle to comply with strict diet alterations. Horses, on the other hand, will complain far less about a diet change and are unlikely to be able to sneak that extra candy bar or bowl of ice cream, making these sorts of studies far easier in horses.”
As for Dr. Hassel, she sees a bright future in human medicine regarding the microbiome, just as she does with horses. “I’m familiar with much of the research on humans and the correlation of microbiome population changes with particular disease states, including cancer, obesity, immune-mediated diseases, GI disease and neurologic diseases to name a few,” she says. The implications of such theories are indeed exciting and could forever change the face of medicine. Dr. Hassel continues, “also, there is certainly a large amount of evidence linking gut health to brain health.” Dr. Whitfield shares Dr. Hassel's enthusiasm, “his is a fascinating area,” he says. “It seems that every day there is a major paper linking the human microbiome to a new disease. What I have found most interesting is that it seems the early, neonatal microbiome is critically important in people.” He’s referring, of course, to findings that suggest that the manner in which infants are born sets the stage for the health of their microbiome. “Study after study have shown that the method of birth — C-section vs. natural — and early use of antibiotics in people has a major impact on diseases later in life that are apparently due to differences in the early microbiome,” he says. “Similar findings are true in children where exposure to ‘dirty’ environments and owning pets at a young age appear to protect from any number of autoimmune diseases.”
“My passion for the horse led me down the path of veterinary medicine from a young age,” says Dr. Hassel. “I am inspired every day by learning something new and will always consider myself a student. The research is just one of the ways that I continue to learn, but the greatest attribute of research is the ability to share the data to make a positive impact worldwide on the health of the horse.” Throughout her career, Dr. Hassel has conducted studies that have helped change the face of veterinary medicine, yet the microbiome may be her most important frontier. “I was instantly mesmerized by microbiome research when I learned about the initial studies in human health and the links of the microbiome to multiple disease states. As an avid triathlete, I am very interested in ways I can improve my health, recovery from training and performance through a healthy microbiome. As a colic surgeon and criticalist, I see the incredible potential to improve horse health as well.”
For Dr. Cohen, his interest in veterinary medicine started with the purest of motivations, the love of the horse. His father, who passed away just last month, was an equine veterinarian and a significant influence on Dr. Cohen’s life and decision to pursue equine medicine. “I have a deep desire to be around horses, and as much as I love animals, I would not be a veterinarian other than to be an equine veterinarian.” It was that deep love of horses that also spurred a passion for research. “I realized that there was a lot we needed to know,” says Dr. Cohen. “I came to the conclusion that I would have a greater impact on horses by doing research to solve health problems than by treating individual cases. Research is humbling but intriguing, and I come to work every day with excitement about what I will learn.”
For Dr. Whitfield, it was the connection between horse and human that inspired him to become an equine veterinarian. After working at a horse farm during his college years, he recognized the therapeutic nature of the horse and human relationship and how people responded to the horses they loved and worked with. “I thought that being a veterinarian would allow me to have exciting daily interactions with clients and horses, and that by helping these horses, I could indirectly help those people that the horses were helping,” he says. His love for practice made him apprehensive to venture into research, though it's a move he now considers to be one of his best decisions. “I continue to get enjoyment out of being a clinical veterinarian, but I feel that through research I may have a broader impact. I hope that one day my research will not only benefit horses but that what we discover in horses may be translatable to people.” The equine microbiome is one such area where Dr. Whitfield sees the potential for monumental discovery, impacting not only the horses he loves but people as well. “It’s a new and exciting area of importance in numerous diseases from brain function, gastrointestinal health and everything in between.”
by Jessie Bengoa,