Research into potential probiotic wormer in horses scores federal cash

Bacillus thuringiensis under 1000X magnification. Image: Dr Sahay/Wikipedia
Bacillus thuringiensis under 1000X magnification. Image: Dr Sahay/Wikipedia

Research into a possible probiotic wormer for horses has received a massive boost, with news that further work will be funded under a $US2.1 million federal grant.

An innovative crowdfunding campaign to pay for initial research was crucial  in the funding application. It helped pay for preliminary research that provided promising data to support the application.

Martin Nielsen, an equine parasitologist, veterinarian and assistant professor at the University of Kentucky’s Gluck Equine Research Center, said he was excited about what lay ahead.

Nielsen spearheaded the crowdfunding campaign to raise money for research into the potential of a crystal protein produced by a soil-dwelling bacterium, Bacillus thuringiensis, to kill equine parasites.

“The money we raised in the crowdfunding campaign was used on running some pilot studies to show the effect of the bacterial dewormer against horse parasites,” he said.

“We had some very promising results.

“These results were then included in a big collaborative research grant application that went to the US Department of Agriculture.

“The competition for these grants is very tough, and many good proposals get turned down every year. We were in fact turned down the first year, but improved the application by adding more of our preliminary data and resubmitted again the year after.

“This time we were successful.

“This is a big five-year grant that will allow us to test the bacterial dewormer in horses.”

Dr Martin Nielsen with horses at the University of Kentucky's Maine Chance farm. Photo: Steve Patton, University of Kentucky
Dr Martin Nielsen with horses at the University of Kentucky’s Maine Chance farm. Photo: Steve Patton, University of Kentucky

Nielsen thanked those who backed the crowdfunding campaign, launched in 2014, which was called “Let the germs get the worms: Testing a novel probiotic compound for treatment of equine parasites.” It raised more than $US12,000.

The $US2.1 million grant from the US Department of Agriculture will cover a range of species. The aim of the research project is to develop and evaluate the bacterial agent for parasite control in horses, sheep, goats, cattle and pigs, as well as humans. Nielsen’s laboratory will evaluate it in horses, while other collaborators will assess it in other animals.

Intestinal parasites can cause significant problems in large farm animals. In addition, more than 1.5 billion people are infected by parasites, some of whom develop serious health issues as a result.

The cash raised by the crowdfunding was used for research in which strongyle parasite larvae were cultured in the lab and exposed to different doses of the protein that Bacillus thuringiensis secreted.

“Here at the university we have a population of parasites that has never been treated with any type of dewormer, and another one that is resistant to two out of three drug classes,” explained Nielsen.

“We tested our bacterial protein against both of these parasite strains.”

The research showed that the crystal proteins secreted by these bacteria were effective in killing both drug-naive and drug-resistant parasites. The research also provided some information on what concentrations were needed to be effective.

The crucial findings were submitted in the federal funding application that ultimately proved successful.

The protein molecule produced by Bacillus thuringiensis is called Cry5B.

Nielsen and his collaborator, Raffi Aroian, a professor at the University of Massachusetts Medical School, hope that B. thuringiensis could ultimately be the genesis of a probiotic wormer – a product that would be welcomed by the growing number of horse owners determined to keep things natural.

Nielsen stresses there is a long way to go from a substance that shows promise as a wormer to something which is proven safe and suitable for wider use.

There has not been a new family of equine dewormers in more than 30 years, and all are prone to some level of resistance from equine parasites.

Martin Nielsen
Martin Nielsen: “We had some very promising results.” ©: Jan B. Jensen

Veterinary science has four classes of dewormers available to kill parasites in horses, the oldest dating back about 50 years. Some are proving far less effective these days, due to resistance, and some work against only some parasites, or on parasites during only certain phases of their life cycles.

Even the “rock stars” among dewormers – the broader ivermectin-based family known as the macrocyclic lactones – are gradually falling victim to growing parasite resistance.

Nielsen said no new drugs were currently being developed for use in parasite control in horses, so the equine industry needed new and reliable treatment alternatives.

He said B.thuringiensis was not traditionally part of any probiotic, for animals or people.

Research to date has shown that the protein crystals produced by the bacterium were capable of killing intestinal worms, seemingly without causing problems for the host.

There is already some good data available on its use in pigs, hamsters and mice, with good results, he said.

“The whole concept of the protein produced by this bacterium is not new,” he said. “It is also used now as a non-chemical pesticide in organic farming.”

Nielsen anticipates that any probiotic developed would not contain the bacterium itself, as stomach acid would quickly degrade the given dose.

He expects the probiotic would comprise the spores of the bacterium, which could successfully pass through the acidic stomach, then develop into the bacteria in the gut and produce the parasite-killing protein crystals. It may, he said, be necessary to add some other “good” bacteria to the probiotic to assist in maintaining a healthy balance in the gut.

Nielsen stresses that even if the long path to a viable deworming probiotic proved successful, it would still have to be used correctly.

Even though of natural origin, it would still be prone to the development of parasite resistance. Just how quickly that would occur is a matter of guesswork at this stage.

“Biologically, we can’t expect to develop any modality in which worms cannot develop some resistance. Chemical or non-chemical, there will always be an active ingredient to which parasites can develop resistance.”

Any probiotic would be in the same boat as any other dewormer, he said.

“We will have to be careful not to overuse it.”

Nielsen said the success to date showed how crowdfunding could play a significant role in getting research funding.

“In addition to the publicity generated during the active campaign, crowdfunding provided a stepping stone for getting a larger grant,” Nielsen said.

“With the limited amount of grants available for equine research, we need to be more entrepreneurial in our fundraising efforts. Crowdfunding represents one such strategy.”

David Horohov, who chairs the Department of Veterinary Science and is director of the Gluck Equine Research Center, commended Nielsen for his initiative and efforts. Nielsen, he said, had shown initiative and entrepreneurship in procuring the funds.

Raffi Aroian is the principal investigator of the USDA grant. Nielsen and researchers from Virginia Tech University and USDA, Beltsville, are co-principal investigators.

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