PROMISE SHOWN FOR
IN CVM COLLABORATIVE MICROBIOME STUDY
by Mike Jernigan
Every feline fan knows that comics fat cat Garfield has a lasagna problem, but what if his constant weight battles aren’t just a result of his fixation on an excess of pasta and meat sauce?
That’s not exactly the question Dr. Xu Wang and a team in the Auburn College of Veterinary Medicine are attempting to answer, but their research into the effect of gut microbiota — or the types and amounts of natural microorganisms found in the gastrointestinal tract — on feline weight may eventually help lead to better treatments and outcomes for obese cats, as well as for those for whom excessive weight loss is a different health issue. As part of an effort to better understand the cause and effect relationship between microbiota and obesity, the team sequenced the microbial genomes in the microbiota, collectively known as the microbiome, in a small initial sample of cats housed at the Scott-Ritchey Research Center.
Wang and his team may be Garfield and other fat cats’ best hope for becoming slim and trim. This team is comprised of Wang, assistant professor in comparative genomics in animal health in the Department of Pathobiology at the Auburn University College of Veterinary Medicine and adjunct faculty investigator with the HudsonAlpha Institute for Biotechnology, alongside fellow faculty members Dr. Christopher Lea, Dr. Diane Delmain, Dr. Erin Chamorro, Dr. Emily Graff, Dr. Doug Martin and lead graduate student
Ironically, the obese cat research, which was recently awarded a $34,583 grant from the EveryCat Health Foundation, originally began due to an attempt to determine a cause for excessive weight loss in some cats being treated for GM1 gangliosidosis, a genetic disorder that progressively destroys nerve cells in the brain and spinal cord. Martin and a team at the Scott-Ritchey Center had developed a highly effective treatment for the disease that was also being tested in human trials, but roughly 20% of the cats — and some of the human patients as well — experienced weight issues. Wang thought he might have some idea of the reason.
“The cats under treatment ate a carefully controlled amount of food and were examined thoroughly,” Wang explained. “No underlying health problems that should affect their weight were found. But none of the efforts to improve their weight were effective. Human patients also had issues putting on weight. Taking all these observations and information into consideration, we thought it could be due to their gut microbiota.”
The gut microbiome is the entire collection of microorganisms’ genomes in the gastrointestinal tract. To give an idea of its complexity, the human microbiota consists of approximately 38 trillion microorganisms in total, exceeding even the number of human cells. “The gut microbiome is an integral part of the body,” Wang said, “and has been shown to be involved in critical biological processes like digestion, the metabolic process, the adaptive immune system and even brain function. The effect of gut microbiota on animal physiology is universal, therefore, microbiome research is critical for both animal and human health.
“In addition,” he added, “the gut microbiome has been shown to affect many aspects of disease physiology, including rheumatoid arthritis, colorectal cancer, cardiovascular disease and inflammatory bowel disease. Microbiome composition and function are also directly related to digestive function, as well as nutrient metabolism and assimilation, which play important roles in modulating weight.”
Wang and his team launched a study of the gut microbiomes in the GM1 treatment cats experiencing severe weight loss and soon found some interesting commonalities. However, they needed similar data on healthy weight and obese cats in order to make comparisons. Their resulting study of the microbiomes of both normal and obese cats not only helped them better understand the weight loss in certain GM1 treatment cats — it also may help provide new treatments for obesity itself, a major problem among the U.S. feline population.
In fact, obesity affects around 45% of domestic cats, so Garfield is not alone. Obese cats face a higher risk of insulin resistance, neoplasia, cardiovascular disease and other health problems, and effective drug treatments are lacking. Increased exercise, special foods or reduced calorie diets are often prescribed by veterinarians, but usually with limited results.
Yet some of the bacteria in the obese cats’ gastrointestinal tracts may stack the deck against them. In their initial studies, Wang and his team found several microorganisms in the microbiomes of overweight cats that have been previously associated with obesity. “The most significant candidates include four bacteria types that were increased in these cats and three that were depleted,” Wang said. “We do not know if these represented true causation or were simply an indirect effect. But a human weight loss study performed at the Mayo Clinic revealed two genera significantly linked to weight loss potential and they are the same as in our cat findings. The discoveries in our research have clear translational value based on the human literature, and this would suggest causation.”
Thanks to the EveryCat grant, Wang and his team now intend to follow up on their initial findings by conducting metagenomic sequencing, or mapping of genomes, for all the microbial species found in the microbiomes of fecal samples from a much larger number of fat cats brought in as patients at the college’s Veterinary Community Practice Clinic. “Think of the gut microbiome as similar to a library full of books,” Wang said. “The approach we use for sequencing would be similar to digitizing every single page in every book in the library. This will reveal the functional capacity of each microbe. The purpose is to validate our findings in a much larger sample size of the general domestic cat population. Some results may hold, but we may also discover some novel findings in the EveryCat study.”
Sequencing those additional genomes, or digitizing that library, will allow the researchers to better understand the role each species plays in obesity, which in turn should help formulate new strategies for weight loss for both cats and — hopefully — humans. “The findings from this study,” Wang said, “will be critical in informing new weight management strategies for obese cats, including evaluations of specific diets that alter gut microbiome composition, the development of prebiotics and probiotics promoting the increase of beneficial microorganisms and the reduction of those associated with obesity and potential microbiome transplantation between obese and lean cats.”
With luck, the study may also benefit some of the owners of fat cats like Garfield, who also enjoy a little too much lasagna. It is yet another application of the One Health concept linking animal and human health. “The bacteria we have identified so far in our study have also been shown to affect weight loss success in human patients,” Wang concluded. “There are definitely some possible applications to human obesity.”