Boosting farm animal health with beneficial microbes

Is it possible to swap out one solution for its opposite and achieve the same r­esult? Livestock farmers are about to find out.

For generations, farmers have used antibiotics to improve production of their chicken, pig, and cattle operations. With use of certain antibiotics on the chopping block because of concerns about the rise of resistant organisms, some are turning from anti to pro—probiotics, that is.

Probiotics, live microorganisms that are a staple of the human wellness industry, have the potential to fulfill many of the roles that antibiotics play down on the farm. Research suggests probiotics can help chickens, pigs, and cows quickly put on weight, efficiently digest feed, and withstand the infectious organisms that tend to lurk wherever animals are kept in close quarters.

But farmers have several ways to raise healthy livestock without relying on antibiotics. They can add enzymes to feed, choose different breeds of animals, and institute new infection controls, to name a few. Many are skeptical that microbes are worth the price.

Probiotics purveyors counter that their newest products, developed with cutting-edge genomic and modeling tools, are well on their way to proving their value. The field is led by firms with both animal nutrition and fermentation capabilities—namely, Evonik Industries, Chr. Hansen, DuPont Danisco, Kemin Industries, and Biomin. And at least one start-up, Ascus Biosciences, has jumped in with a unique approach for dairy cows.

Evonik develops and sells bioactive feed additives like enzymes, prebiotics, organic acids, and plant-based compounds such as essential oils. “But our main focus is probiotics because as living organisms they have multiple modes of action,” says Stefan Pelzer, Evonik’s director of innovation management for animal nutrition.

Other feed additives can do one thing well, but Pelzer says probiotic microbes are like a Swiss Army knife—good for many situations. “They cover a lot of the challenges of our customers.”

To do battle with bad bugs, companies have enlisted genera and species familiar to those who read the labels of probiotic supplements marketed to people: Lactobacillus, Bifidobacterium, Bacillus, Enterococcus, Aspergillus oryzae, Saccharomyces boulardii, and Saccharomyces cerevisiae.

It is still early days in their adoption for animal health, company experts say. Yet sales surpassed $1.2 billion in 2017 and are expected to grow by 6.5% per year through 2022, according to the market research firm Frost & Sullivan. By comparison, sales of probiotic ingredients for human food and beverages total almost $2 billion per year.

Marketers see the use of probiotics accelerating as livestock farmers, particularly in the US, drop antibiotics like a hot potato. Sales of agricultural antibiotics deemed medically important for human use plummeted 33% from 2016 to 2017, according to the US Food and Drug Administration. They’re down 43% from 2015, the peak year for sales.

By volume, the biggest drop has been in the tetracycline class of antibiotics, agricultural sales of which reached 6,881 metric tons in 2015. Other classes on the wane include penicillins, macrolides, sulfas, and aminoglycosides.

As early as 1970, public health researchers and government scientists had fingered the use of such drugs in animals as a cause of the rise of antibiotic-resistant bacterial infections in humans. Until recently, efforts to restrict their use in the US were voluntary. Then in 2017 the FDA issued a guidance on the judicious use of antimicrobials in food-producing animals.

The European Union banned the use of antibiotics as growth promoters in 2006, following the lead of Sweden, which began to crack down in the 1980s. Sweden’s experience shows that the transition away from routine use of antibiotics can be tough.

According to the United Nations Food and Agriculture Organization (FAO), broiler chickens and baby pigs in Sweden were felled by deadly outbreaks of bacterial gut illnesses when the cutbacks were first made. In addition, animal growth rates slowed. In the long run, though, Sweden was able to improve animal welfare overall, the organization concluded.

In a more recent report, FAO weighed the evidence for a move to probiotics. It evaluated research on the products’ effects on animal performance and on the prevention and control of pathogenic organisms like salmonella, campylobacter, and Escherichia coli.

FAO found that probiotics can change the population of gut microbes by outcompeting undesirables or knocking them out with antimicrobial substances. The good microbes also adhere to the intestinal lining, where they can prevent pathogens from sneaking into the bloodstream. They keep the immune system on alert but tamp down the inflammation response.

Probiotics also produce handy enzymes like amylases and proteases that help animals digest the carbohydrates and proteins in feed. Strangely, probiotics also increase the height of intestinal villi, increasing the surface area for nutrient absorption.

Overall, FAO says probiotics are a viable substitute for antibiotics. They can improve growth rates and prevent disease. “However,” the report notes, “the outcomes from probiotic use are not consistent.”

Evonik’s Pelzer acknowledges that probiotics have a reputation for being unreliable, but he says that can be due to quality control. He claims to have spotted underdosing and contamination in products on the market. In addition, certain strains of the same species are better than others. “We are all Homo sapiens, but few of us are able to run a marathon—it’s the same for Bacillus subtilis,” Pelzer says.

To find its candidate strains, Evonik scientists take samples from soils and farms. To choose the best ones, they study the interactions among animal feed, immune systems, and gut microbiomes. Evonik can tweak these variables in a physical model of the poultry gut it calls DAISY, for dynamic avian intestine in vitro system. It’s a concept borrowed from human health research.

Also borrowed from human research are tools to look inside the microbe, including “bioinformatics, genomics—all the ‘omics,’ ” Pelzer says. For example, to understand how a star strain competes for resources in the gut, Evonik turns to metabolomics. Only the strains that work well in combination with other feed additives are tested in animals.

Probiotics for various farm animals tend to be made of strains from the same handful of microbe species. At the start-up Ascus Biosciences, cofounders Mallory Embree and Michael Seely felt they could do better.

“The idea was to use more effective microbial genomics to build more effective microbial products,” Seely says. Armed with this idea, they decided to look at the metabolically challenging low-oxygen environment of a dairy cow’s stomach.

Cows rely entirely on microbes to break down the fibrous plant material in their diet. The microbes live in the rumen, the first of four digestive chambers. “The rumen is a vast fermenter. It’s just churning a big churn of feed and microbes,” Seely explains.

Those microbes produce enzymes that break down hemicellulose and cellulose, unlocking energy from the feed for the cow. The bodies of the proliferating microbes also serve as a source of protein. They enable the cow to produce high-value milk from low-value feed. By bioprospecting inside high-performing cows and then using computational tools, Ascus can identify the populations of microbes behind improved milk production, Seely claims.

To develop its first product, Ascus used a method developed by Embree to home in on optimal microbes from 1,600 rumen samples. Out of 55,000 microbes they found, about 10,000 are native to all cows. Of that group, 150 were identified as potential performance-improving organisms.

But microbes that thrive in low-oxygen places like cows’ guts are difficult and costly to cultivate. And there are other hurdles to overcome to develop a stable product that works as a feed additive. Ascus stuck with it and last year launched its first product, which is based on a fungus native to high-performing cows.

The fungus is “really prolific at making enzymes,” Seely says. “Fungi, like on a banana peel that gets covered in mold, are really good at degrading things.” Seely says the company has data from six animal trials showing its product works.

The feed supplement is on the market in Mexico and in South America. Seely and Embree are now prospecting in other animal guts, including beef cattle, poultry, pigs, horses, and dogs.

Ascus’s chief operating officer, Jimmy Owens, has been talking to dairy farmers in Mexico about the company’s product. “Farmers say the market has been waiting for this for 20 years,” he says. “The microbial technology and the funding for animal health and nutrition just wasn’t there.”

Now, Owens says, “The burden of proof is on us. As we get more experience with more animals on more farms and as our success holds up, we feel really good about our prospects.”