Study shines spotlight on equine gut disturbances from intravenous antibiotics

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Antimicrobial therapy has been linked to drug-associated diarrhea in horses, which can have serious consequences.
Image by Manfred Richter

Antibiotics commonly used in horses can alter equine gastrointestinal communities, which could lead to gut disturbances, promote inflammation, and cause diarrhea, researchers report.

Antibiotic use has been linked to antimicrobial-associated diarrhea in both horses and humans, Rachel Liepman and her fellow researchers noted in the journal Animals. In horses, this form of diarrhea can lead to serious complications, including sepsis, laminitis, multi-organ failure, and death.

The North American study team hypothesized that disruption of the gut microbiota after antimicrobial therapy in horses leads to loss of colonization resistance and alteration of the microbial metabolic function which favors gastrointestinal inflammation and pathogen growth.

They set out to determine the effect of intravenous use of three antimicrobials, ceftiofur, enrofloxacin and oxytetracycline, on equine fecal bacterial communities over time.

They wanted to know whether any changes were detectable after five days of treatment and whether they persisted over time, and were still noticeable after 30 days.

Sixteen horses were randomly assigned into four groups comprising four horses. One group received enrofloxacin, one received ceftiofur sodium, one received oxytetracycline, and the fourth received a saline solution as a placebo.

The drugs were given intravenously for five days. Fecal samples were obtained before the start of treatment and then 3, 5 and 30 days into the study.

Molecular-based testing was used to identify the bacteria present.

The fecal microbiota of healthy horses in the study population before drug administration was similar to that reported in other studies, with Firmicutes and Bacteroidetes dominating, and Proteobacteria and Fibrobacter being less abundant.

The researchers said the drug therapy in all cases failed to cause any changes in physical examination parameters, behavior, appetite or fecal output or consistency throughout the study in any horse.

All three antibiotics have a broad spectrum action and have some degree of gastrointestinal excretion. Therefore, an impact on gut microbiota was expected.

The most significant changes to microbial diversity and abundance were found using ceftiofur and enrofloxacin, they reported.

Only minor changes were seen with oxytetracycline compared to the saline group.

The relative abundance of Fibrobacteres was markedly lower on day 3 compared to other days in the ceftiofur and enrofloxacin treatment groups. This bacterial family is essential for the degradation of plant cell wall material into short-chain fatty acids in the horse’s hindgut.

Loss of bacteria able to degrade this material can spark growth of bacteria that metabolize starch (for example, Lactobacillus, Streptococcus and Lachnospiraceae), leading to greater production of lactate and therefore a decrease in pH.

Reduction in colonic pH is associated with damage to the intestinal lining and a decline in commensal bacteria (mutually beneficial species), triggering an inflammatory response.

“Together, these findings highlight the detrimental effect that antimicrobial drugs have on bacterial communities associated with gut health and indicate that changes in specific taxa could predispose horses to gastrointestinal inflammation and the development of diarrhea.”

An increase seen in Clostridia populations and the Lachnospiraceae family from day 0 to days 3 and 5 in the horses treated with ceftiofur and enrofloxacin is of interest, they said, because they play a crucial role in maintaining gut balance.

“In our study, commensal Clostridia could have proliferated, but since absolute counting was not performed in the present study, it is possible that the increase was caused because of the reduction in other taxa.”

The vast majority of Clostridia present in the equine gut are commensals; however, this genus also includes several species associated with gastrointestinal diseases in horses such as Clostridium perfringens and Clostridiodes difficile.

This, they said, is an important observation considering that many clinicians initiate antimicrobial therapy when treating diarrheic horses, and this practice can decrease the relative abundance of important commensals in the gut.

The relative abundance of the Fibrobacter genus and Clostridia class remained similar in horses treated with oxytetracycline or saline during the study period.

This was unexpected because reports published during the 1970s and 1980s, but not recently, suggest that the use of intravenous or oral oxytetracycline in horses carries a higher risk for the development of antimicrobial-associated diarrhea than other antimicrobial drugs.

The researchers noted that information regarding the effects of drugs commonly used in equine practice on the mucosal microbiota is scarce.

“Implementation of therapies that include the use of nutritional supplements, prebiotics, probiotics and fecal microbial transplantation is controversial because of the paucity of evidence of their benefits.

“While anecdotal reports and some studies have claimed clinical improvement of various equine gastrointestinal disorders in response to these interventions, the majority have failed to critically demonstrate benefits.”

In conclusion, the study findings show the negative effect of antimicrobial drugs on bacterial communities associated with gut health and indicate that changes in the abundance of certain kinds of bacteria could predispose horses to gastrointestinal inflammation and diarrhea.

They said it is not only a goal to promote the rational use of antimicrobials and other drugs, but also to implement better antimicrobial stewardship practices.

The study team comprised Liepman, Jacob Swink, Greg Habing, Prosper Boyaka and Ramiro Toribio, all with the Ohio State University; Benjamin Caddey, with the University of Calgary; Marcio Costa, with the University of Montreal; and Diego Gomez, with the University of Guelph.

Liepman, R.S.; Swink, J.M.; Habing, G.G.; Boyaka, P.N.; Caddey, B.; Costa, M.; Gomez, D.E.; Toribio, R.E. Effects of Intravenous Antimicrobial Drugs on the Equine Fecal Microbiome. Animals 2022, 12, 1013. https://doi.org/10.3390/ani12081013

The study, published under a Creative Commons License, can be read here.

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