03 October 2018- The worst-case scenarios of unchecked antibiotic resistance are the stuff of nightmares. People dying from gardening accidents. Surgeries that are routine today becoming unthinkably risky. Life expectancy plummeting. Moreover, today, there is no way to “cure” resistance. We are striving to slow its development by using antibiotics prudently — the emerging field of “antibiotic stewardship”. And frankly, prudence on issues of public health is not always humanity’s strongest suit. It’s worth losing sleep over.

But what if we were able to affect whether bacteria could become more susceptible to antibiotics? That would change the equation. That tantalizing prospect is the focus of research led by Diamond V, a provider of microbial fermentation technology for the animal nutrition industry.

In 2016, the company was working with Iowa State University College of Veterinary Medicine on control challenge studies to examine the effects that their fermentation-based product was having on foodborne pathogenic bacteria and the immune system of various species, including chickens. The studies included an examination of fecal shedding of salmonella and assessments of invasiveness and antibiotic resistance.

“The Iowa State researchers challenged birds with multidrug resistant salmonella,” recounts Dr. Don McIntyre, director of global research and technical services. “They saw the bacteria prevalence go down, they saw the bacteria numbers go down, and then as they measured the antibiotic resistance they were amazed to see the antibiotic resistance in the salmonella go down.

“We had a lot of sceptics here at Diamond V,” he says. “So they did [the experiment] a second time, and it did the same thing. They did it a third time, it did the same thing.” According to him, the company has observed a reduction in antibiotic resistance consistently across 60 tests conducted, and the effect has been seen not only in salmonella but also e. coli and klebsiella.

“That’s one beauty of the immune system,” says Dr. McIntyre. “It’s no respecter of invaders. There’s a generic response [to a wide variety of pathogens].”

There could be many possible explanations for the effect; however, in this case, the researchers determined that they were seeing the bacteria lose an SGI1 integron, a piece of mobile genetic material that is key to bacteria’s encoding of antibiotic resistance. This raised concerns that the integron, once expelled from one pathogen under consideration, would be picked up by another pathogen, causing the resistance to migrate rather than disappear.

“In testing with Diamond V customers, laboratories are checking multiple pathogens [including salmonella, e. coli, campylobacter, clostridium, and klebsiella] simultaneously just to make sure that the genetic resistance is not leaving one pathogen and going to the next. It is not. It apparently goes away,” asserts Dr. McIntyre.

The mechanism for the expulsion of the integron has not yet been determined, although one hypothesis holds that perhaps the immune system of the animal is somehow encouraging bacteria to jettison the integron as it is no longer necessary while continuing to carry it would require other trade-offs. However, this explanation remains highly speculative at this point. Yet, it does seem clear that the immune support product is working through the biology of the animal to help improve susceptibility to antibiotics.

“You cannot spray Diamond V technology on a pathogen [outside of the animal] and kill it,” notes Dr. McIntyre. “It’s not like an antibiotic. It requires a host. It strengthens the immune system so that pathogen recognition is enhanced and natural protection is improved.”

To better understand both the veterinary and public health potential, it was eminently important to determine how widely applicable the solution might be. According to Dr. McIntyre, tests have found that the technology decreases resistance to all 14 antibiotics surveilled in the NARMS (National Antimicrobial Resistance Monitoring System) study of antimicrobial resistance in the United States. Diamond V and multiple university researchers have also conducted tests across various commercially relevant food animals, including broilers and layers, turkeys, swine, and beef and dairy cattle.

Going forward, Diamond V plans to focus on confirming which other pathogens might demonstrate the same decrease in antibiotic resistance and checking whether the effect is the same for resistance to antibiotics with different modes of action. Additional efforts will be devoted to understanding the mechanism behind the expulsion of the integron. And of course, the company itself remains interested in pursuing its original question of how its microbial fermentation technology supports the immune system—including, potentially, against viruses.

Meanwhile, as Diamond V continues to explore the mode of action behind reduced antibiotic resistance, the company is also beginning to look at how its discovery will be marketed. The possibilities are tremendous, as stakeholders at every level have an interest in the use of a product that could deliver on this potential—from the farmers who could hope to see fewer sick animals and more effective therapeutic interventions, to the retailers who are looking to deliver food products “raised without antibiotics” and reduce the number of costly recalls, to the public health officials who would be relieved to see the incidence of antibiotic-resistant illnesses decline. Diamond V says they have already filed for use patents in the US, based on their technology’s capability to help mitigate antibiotic resistance and reduce the risk of foodborne pathogens in food animals. The company is focusing on authorizations to make this claim in the EU next.