Over the past decade or so, scientists have discovered that a poor gut microbiome is linked to many diseases, so how to increase beneficial gut bacteria has become a hot research topic among scientists. In fact, gut health is also very important for livestock. To reduce the use of antibiotics, recently a research team from the Department of Biotechnology and Animal Science at National Ilan University has actively conducted research and found that using composite Bacillus fermentation metabolites can strengthen pigs' resistance to intestinal diseases and has the effect of replacing intestinal antibiotics.

Digestive tract diseases are a high-incidence disease in livestock, especially in pig herds, and are also an "invisible killer" of safe pig farming. The traditional practice of pig farmers is to have pigs injected with antibiotics, but this approach may cause pigs to develop drug resistance.

Taiwan's pig farming industry is well developed, and its pig farming technology is quite advanced, with excellent results in both breed improvement and disease resistance. However, limited by land resources, overly intensive farming, combined with the island's hot and humid climate, makes the crowded environment prone to breeding pathogens and easily causes growing pigs to become infected with respiratory and intestinal pathogens.

Composite Bacillus Fermentation Metabolites

Solving the Drug Resistance Problem With Potential as an Antibiotic Alternative

In order to reduce the use of antibiotics, along with advances in agricultural technology, there are now many ways to enhance pigs' resistance. Especially in the field of animal nutrition, the development of new feed additives, such as microorganisms with special functional properties, is currently a main focus of biotechnology research and development.

Just like the human gut, improving the gut microbiome also helps enhance the health of pigs. In response to global demand for livestock products free of antibiotic residues and to reduce environmental problems, probiotic products are used as feed additives to stabilise the animal body's gut microbiome, improve gut health to reduce digestive tract diseases or further enhance the animal body's immunity, so that all bodily functions of the animal can be comprehensively improved, achieving a preventive healthcare effect.

Recently, a research team from the Department of Biotechnology and Animal Science at National Ilan University, under the leadership of Professor Cheng Yung-hsiang, began research in 2012 on "using composite Bacillus fermentation metabolites to strengthen pigs' resistance to intestinal diseases," and applied for the project in 2014, hoping through this project to develop composite Bacillus fermentation products and metabolite identification as a zinc oxide alternative, solve the problem of post-weaning diarrhoea in piglets, while also controlling the new PED epidemic in piglets, reducing enveloped virus infection, and completing the replacement of antibiotics to control pathogenic intestinal diarrhoea in piglets, increase piglet survival rates, and also ensure the safety of livestock products.

In this regard, Cheng Yung-hsiang further stated, "Many recent studies mostly focus on gut health and optimal immune function." For example, enterotoxigenic E. coli (ETEC) mostly occurs in newborn piglets and weaned piglets, with main symptoms including diarrhoea, cyanosis of the ear flaps and limbs, sunken eye sockets, loss of appetite or refusal to eat, neurological symptoms and rapid breathing. Lesions are also mainly characterised by relaxed or thinned small intestine walls filled with watery fluid, congestion and haemorrhage of the stomach, small intestine and large intestine, oedema of the large intestine, enlarged and haemorrhagic lymph nodes, interstitial pneumonia and meningeal congestion, with an incidence rate between 30% and 80%, a mortality rate of 6.6% to 100%, and occurrence in all four seasons. However, it was found that in addition to ETEC having developed resistance to Colistin and Gentamicin in drug susceptibility tests, ETEC isolated by the Department of Veterinary Medicine at National Taiwan University was also found to have multidrug resistance.

In addition, the amount of zinc oxide routinely used internationally and domestically to reduce post-weaning diarrhoea in weaned piglets has also been reduced from the original 3000ppm to 130ppm. The legislative amendment mainly takes environmental and food safety into consideration, and further declares this wave of antibiotic and zinc oxide alternatives as a trend in livestock and poultry farming applications.

To break through this problem, the National Ilan University research team accidentally discovered that Bacillus fermentation metabolites have the development potential as a zinc oxide alternative. "Bacillus species are classified as generally recognised as safe (GRAS) strains, and therefore are permitted for use in the food industry. There are many commercial products that can be used as nutritional additives for humans and as feed additives for livestock and poultry. Through Bacillus vegetative cells and spores, Bacillus can stimulate the immune system in the gastrointestinal tract." Cheng Yung-hsiang further added, "In the past, we have successfully produced the lipopeptide Cyclolipopeptide from composite Bacillus, and confirmed its structural formula via HPLC and LC/MS. After understanding that surfactin can replace zinc oxide's effects in intestinal astringency and reducing inflammation, we then conducted in vitro tests targeting the lipopeptide's ability against PEDV, evaluating the effects of different doses of lipopeptide at different action times on PEDV's ability to infect green monkey cells. At the same time, pig trials were also conducted to evaluate the ability of feed supplemented with this probiotic-produced lipopeptide against PEDV infection and harm in pigs, and pathological examinations of the trial pigs were conducted to evaluate the safety of long-term use of this probiotic-produced lipopeptide in pigs."

Industry-Government-Academia Collaboration on Technology Transfer to Accelerate Development and Application and Seize Market Opportunities

Research results show that in addition to the Bacillus fermentation product significantly improving the four-week-old body weight gain of weaned piglets compared with the control group, the PEDV+lipopeptide group had milder clinical symptoms and a slight reduction in daily viral shedding compared with the PEDV group, and both IgG and the Lactobacillus group in the faecal microbiome were significantly higher in the composite Bacillus group than in the zinc oxide group.

Although there has already been a technological breakthrough, Cheng Yung-hsiang stated that there is still considerable room for effort in the development and application of composite Bacillus fermentation metabolites. "In addition to requiring larger-scale field tests, we also need more funding to invest in equipment. The fermentation equipment alone requires an investment of several million. However, the market opportunities here are unlimited. Industry-government-academia collaboration can accelerate the development process and also expand from livestock to poultry. At the same time, it is in line with international trends. This kind of microbial preparation will be widely used in healthy livestock and poultry farming, providing consumers with more safe and reassuring livestock and poultry products."

Related Information

To learn more about the details of this project's research and development results, please contact Mr. Ho at the Agricultural Technology Research Institute, telephone: 03-5185049, email: [email protected]