How Phenylbutazone, Firocoxib Affect Horses' Gut Microbiota
Veterinarians commonly administer non-steroidal anti-inflammatory drugs (NSAIDs) to relieve pain and inflammation in horses. One of the side effects of these drugs, however, is gastrointestinal (GI) issues such as gastric ulcers or right dorsal colitis. In humans and other species there is evidence that these drugs might induce GI microbial imbalance, but we don’t yet know if they alter horses’ microbiota.

So Canaan Whitfield-Cargile, DVM, PhD, Dipl. ACVS, ACVSMR, and a team of researchers from the Texas A&M University’s College of Veterinary Medicine and Biomedical Sciences conducted a study to compare the effects of the COX-2 selective NSAID, firocoxib, and the nonselective NSAID phenylbutazone on fecal microbiota composition and diversity in adult horses. They presented their results at the 2017 American Association of Equine Practitioners convention, held Nov. 17-21 in San Antonio, Texas.

First, let’s review how NSAIDs work. These drugs reduce prostaglandin (chemicals that can promote inflammation, pain, and fever) production in the body. Not all prostaglandins, however, are bad. Some protect the gastric lining from damage caused by stomach acid and promote blood clotting by activating platelets.

Prostaglandins are produced by enzymes called cyclooxygenases (COX), of which there are two main types: COX-1 and COX-2. COX-1 helps protect the GI tract lining by promoting mucous production and blood flow. COX-2, on the other hand, is upregulated under certain circumstances and is responsible for production of prostaglandins associated with inflammation, resulting in clinical signs such as pain, swelling, and fever.

The two classes of NSAIDs are COX-2-selective and nonselective. While both classes of NSAIDs can cause GI injury in humans and animals, COX-2 selective NSAIDs might cause less severe injury.

Trillions of organisms make up the equine hindgut microbiota—the GI tract from the large intestine backward. In fact, microbial cells in the digestive tract far outnumber the tissue cells that make up the horse’s body. Altering the GI microbiota might affect a horse’s overall health and disease severity.

In Whitfield-Cargile’s study, his team randomly assigned 10 adult horses to one of two treatment groups (firocoxib administered at 0.1 mg/kg once a day or phenylbutazone at 4.4 mg/kg once a day) and five horses to a control group that received a placebo treatment. They administered treatments for 10 days and collected fecal samples on Days 0, 5, 10, 15, 20, and 25. Then they extracted DNA from the feces and sequenced it to determine microbiota composition and diversity.

Results showed that the control group’s fecal microbiota remained stable over the course of the study. However, both treatment groups’ microbial diversity decreased, most significantly on Day 10. The changes were similar for both firocoxib and phenylbutazone. Specifically, the microorganisms they lost were Clostridiaceae and Lachnospiraceae, which are involved in mucosal homeostasis (stability/balance). Past studies have shown their numbers to be higher in healthy horses than in horses suffering from colitis. Therefore, a reduction in these microorganisms can potentially impact horse health.

In addition, they also noticed a decrease in the fatty acid butyrate, which is an important energy source for horses.

“Owners and veterinarians should consider the potential impacts of these (microbiota) changes when administering NSAIDs to their horses and limit duration of NSAID use to prevent or limit the impact of these changes,” said Whitfield-Cargile.

The researchers cautioned that they conducted this study using a relatively small sample size and a closed group of healthy horses. Results could have been different if the horses had other health issues. Additionally, the team only investigated one treatment dose of each drug. Researchers need to investigate other dosages and determine the clinical significance of these findings, said Whitfield-Cargile.