Gut Risks Related to Use of NSAIDs in Horses Confirmed By Texas A and M Study

Dr. Canaan Whitfield-Cargile and colleagues from Texas A & M and Baylor University recently conducted the largest study to date examining the effects of NSAIDs on the gut health of horses.

WHAT ARE NSAIDs?

NSAIDs are non-steroidal anti-inflammatory drugs commonly used to treat pain and inflammation in both animals and people. But, gastrointestinal problems have been linked to NSAID use, and it was thought this might be due to the drugs causing an imbalance in the healthy bacteria that lives in the gut – a condition called dysbiosis. In horses, dysbiosis can cause serious problems such as colic, toxicity, protein loss, diarrhea, gastric and oral ulcers, right dorsal colitis, and renal papillary necrosis.

HOW DO NSAIDs WORK?

NSAIDs target an enzyme called cyclooxegenase (COX) which is responsible for creating an inflammatory reaction in the body. There are three varieties of cyclooxegnease (COX-1, 2 & 3). COX targets the arachidonic acid found in cell membranes, converting it to prostaglandins. Prostaglandins occur at the site of tissue damage or infection, where they can cause inflammation, pain, and fever as part of the healing process. They can cause stiffness and pain after strenuous activity, or swelling and even tissue deformity. In horses with degenerative joint disease or arthritis, over time prostaglandins can cause fluid leakage from the joints (joint effusion) which can result in a shortened stride or limp.

TWO TYPES OF NSAIDs

The first NSAIDs on the market were non-selective, meaning they worked by targeting all types of the COX enzymes. This meant they were effective in reducing inflammation, but they also reduced COX-1 enzyme levels which are essential to a healthy digestive tract.  As harmful side-effects of non-selective NSAIDs came to light, other drugs targeting only the COX-2 enzyme called COX-2 selective inhibitors were developed. It was thought by targeting COX-2 and protecting COX-1, the digestive system would be preserved. 

THE RESEARCH

In his study, Texas A & M professor Dr. Whitfield-Cargile wanted to find out if digestive bacteria (microbiota) in horses were altered by use of NSAIDs, and if there was any difference in the effects of non-selective vs. COX-2 selective NSAIDs.

Horses in the study were randomly separated into 3 groups. The first was given phenylbutazone (non-selective NSAID), the second was given firocoxib (the only FDA-approved COX-2 selective NSAID available in the U.S. for equine use), and the third group acted as the control and received no medication. Treatments were given for 10 days, and fecal samples were collected from all the horses every 5 days for 25 days. The samples were then analyzed to determine what types of microbiota were present.

THE FINDINGS

As predicted, the control group experienced no change to the composition of their microbiota. However, both the horses that took phenylbutazone and those that took firocoxib experienced a decrease in the variety of gut microbes. The study determined that changes to gut bacteria caused by both COX-2 selective and non-selective NSAID use were significant because they are linked to serious equine diseases such as colic, colitis, laminitis, and gut infections.

The study authors concluded, “Our findings suggest that, in horses, both selective and non-selective COX inhibitors result in similar dysbiosis.”

“Given the frequency of use of this class of medication, understanding their impact on the equine microbiota is clinically important because alteration of the gastrointestinal microbiota has been linked to inflammatory diseases including colitis and laminitis.”

CONCLUSIONS

 So, what are some takeaways from this research?

• First, if your vet recommends administering NSAIDs, talk to him or her about any pre-existing conditions your horse may have that could be negatively impacted by the potential side effects of NSAIDs.
• Second, consider alternative holistic therapies that could improve your horse’s condition without the use of prescription medications.
• Lastly, consider trying natural anti-inflammatories like Technyflex® with New Zealand Greenlipped Mussel that reduces inflammation effectively without causing any harmful side effects.

Whitfield-Cargile CM, Camoun-Emanuelli AM, Cohen ND, Richardson LM, Ajami NJ, Dockery HJ (2018) Differential effects of selective and non-selective cyclooxegenase inhibitors on fecal microbiota in adult horses. PLoS ONE 13(8): e0202527. https://doi.org/10.1371/journal.pone.020527