Microbiomes and Metagenomics
In recent years, there have been remarkable advances in our understanding of the complicated and critical relationship between the mammalian host and the teeming population of microorganisms with which it is invested. The newly designated University of Missouri Metagenomics Center (MUMC) places those of us interested in equine gastrointestinal health in an especially good position to take advantage of this modern technology and to apply it for the health benefit and welfare of our equine patients.
The term microbiome (or microbiota) has been adopted to represent the ecological community of commensal, symbiotic and pathogenic microorganisms (including bacteria, fungi, worms, protozoa, and viruses) that share our body space. For example, the human microbiome consists of approximately 100 trillion microbial cells that outnumber human cells by a factor of 10 to 1. Thinking of it in terms of the number of genes that it brings to the table, the microbiome of the human gastrointestinal system consists of approximately 3.3 million genes — an enormous number when compared to the paltry 25,000 genes that are responsible for the biological composition of the human organism. As such, the gastrointestinal tract microbiome represents one of the most complex microbial ecosystems anywhere in any environment.
The understanding that the microbiome is directly involved in the health maintenance of its host has led to it being referred to as the “forgotten organ.” Any individual (human or horse) possesses different microbiomes at different locations of the body. For example, a complicated and diverse population of bacteria lives on the skin and is essential for cutaneous health. The skin microbiome is further differentiated by location such that the population of bacteria on the face is distinctly different from that on the fingers, for example.
Although the newborn baby or foal is sterile or devoid of microorganisms within the confines of the intra-uterine environment, it quickly establishes discrete and diverse microbial populations following exposure to the female parent’s vaginal, perineal and skin microbiotas. These initial colonizers or “pioneer” microbes rapidly establish themselves in the newborn and create the organ-specific microbial populations that will, in health, predominate throughout the individual’s life.
Many medical conditions have been linked to changes in status of the gastrointestinal microbiome, especially in people. The lay press regularly reports new disease associations to the microbiome. Specific disruptions of the gastrointestinal microbiome have been reported in the context of many chronic human bowel ailments, including ulcerative colitis, Crohn’s disease, irritable bowel syndromeand celiac disease. Hospital-acquired Clostridium difficile enterocolitis, which is also a problem for horses and foals, is a commonly reported and potentially fatal complication of antibiotic use.
These cases represent an especially devastating disruption of the microbiome and, in some cases, have been successfully solved by administering fecal microbiota from a healthy person to the patient when antibiotics had failed. The influence of the gastrointestinal microbiome on health extends beyond the intestinal tract, and specific changes in the microbiome have been linked to the development of obesity, risk for diabetes, autism, Alzheimer’s disease, atherosclerosis, chronic fatigue syndrome and some forms of cancer.
Key to the recent explosion of knowledge depicting such a powerfully intimate relationship between the microorganisms of our bodies and the state of our health has been the development of next generation sequencing or NGS. This method has allowed scientists to identify and characterize the vast population of microorganisms that inhabit the body in an affordable and rapid manner. This method employs a DNA fingerprinting approach in which the genetic identity of microorganisms can be determined and catalogued using polymerase chain reaction technology.
Prior to the introduction of NGS, microbial identification was largely based on methods that depended on laboratory propagation or cultivation. Frustratingly, the majority of organisms are simply not cultivable in the laboratory or the specific conditions for laboratory growth are time consuming, complex and impractical, often requiring distinctive and precise conditions for each organism. The MUMC acquired the equipment for ultra-fast NGS and introduced and encouraged its employment to help answer questions about the microbiome in different species.
The existence of the horse itself is predicated on the health of a substantial large intestinal microbiome for nutrient derivation from their grass/forage-based diet; therefore, we wasted no time in moving ahead with a project to map the microbiome along the entire length of the equine gastrointestinal tract.
Using this approach, we plan to develop knowledge and a basis upon which to better understand certain types of gastrointestinal disease. For example, a causative explanation for the majority of horses that are presented to our hospital for treatment of diarrhea and colitis cannot be identified, even following extensive and sometimes expensive testing and a post-mortem examination. Although well-known causes for diarrhea may be identified in a few cases (such as for salmonellosis and Potomac horse fever), tests for known pathogens lead to negative findings in most cases. This observation has led us to the hypothesis that a professional pathogenic microbe may not be responsible for diarrhea in most instances and that a non-specific shift in the relative proportion of different groups of microorganisms within the microbiome may represent the cause of diarrhea in most instances. Such a population rearrangement has been termed dysbiosis. This newer NGS technology represents an insightful method to study gastrointestinal dysbiosis in horses, and our team is well placed for this purpose.
Ultimately, we hope to identify novel changes in the gastrointestinal tract microbiome that may have relevance to equine intestinal disease conditions such as colic, diarrhea and even laminitis. We’re also interested in the potential link between the equine gastrointestinal microbiome and risk of obesity, insulin resistance (equine metabolic syndrome) and endocrinopathic laminitis. There is great hope and evolving evidence that specific micro-organisms usually bacteria can be engineered so that, when added to the intestinal microbiome as a probiotic, they can provide specific treatment advantages for the patient. Work in mice has shown that engineered bacteria can help regulate glucose during the treatment of diabetes. There probably isn’t another mammalian species in which the health and composition of the large intestinal microbiome is more essential to the well-being of the mammalian host than that of the horse.
There is so much to be learned and there are so many potential areas in which veterinarians need help to do a better job for our equine patients affected by crippling gastrointestinal diseases that we’re really excited to get started with this line of investigation. We welcome any questions and conversations about this potentially very important new line of investigative clinical research. We welcome any gifts to facilitate our studies.
