Key Points

Ionophores are nutritional tools used to alter ruminal fermentation dynamics and improve the efficiency and performance of cattle. The most common ones used are laidlomycin, monensin, narasin, salinomycin, and lasalocid.

 

Ionophores regulate the ruminal environment by modifying the metabolism of gram-positive bacteria, increasing the concentration of propionate, and reducing acetate. They are also used to alleviate ruminal proteolysis, which has a direct impact on the reduction of ammonia synthesis. This increases the influx of protein into the small intestine, improving performance and efficiency responses. Their use also reduces the substrate needed for methane production, indirectly modulating ruminal methanogenesis.

 

There are concerns regarding their use, especially their impact on microbial adaptation. Their safety margins for use are very narrow, and toxicosis is usually not visible until
multiple days after dosage.

What are ionophores?

 

A category of antimicrobials, ionophores are carboxylic polyether antibiotics naturally produced by an occurring strain of Streptomyces spp. They are capable of moving ions across biological membranes, both cellular and organelle, as well as down concentration gradients. An example would be the movement of monovalent cations such as calcium and sodium across the cell wall in exchange for potassium and hydrogen ions. 

 

There must be a concentration gradient for translocation to occur from a higher concentration to a lower concentration. Ion gradients are maintained by energy-driven membrane pumps. When ions move across a cell wall, there is a multitude of events to try to re-establish the ion gradients. This can result in cell damage and death.

 

Mode of action

Ionophores are lipophilic molecules, with a capacity to adhere to bacteria and protozoa membrane. gram-positive bacteria do not have a protective membrane and are thus more sensitive to ionophores. In general, these produce acetic acid, butyric acid, lactic acid, and methane. Most bacteria have a high intracellular potassium and a low intracellular sodium concentration, making their intracellular environment more alkaline. The ruminal environment, in turn, contains high sodium and low potassium, and slightly acidic pH due to volatile fatty acid (VFA) concentrations. Rumen bacteria will thus rely on the ion gradient balance between sodium and potassium to maintain a healthy intracellular environment.

 

When ionophores are added to the diet, they will insert into the lipid membrane of rumen bacteria and disrupt the ion balance by acidifying the bacterial environment. To try and counter this, the bacteria activates sodium/potassium and hydrogen ATPase systems, pumping these protons out of the cell. This, however, depletes intracellular ATP during the removal of hydrogen ions, reducing cellular viability.

 

Gram-positive organisms in the rumen are inhibited, allowing gram-negative organisms to predominate. Gram-negative bacteria produce succinate and propionate acids. The increase in the rate of gain and feed efficiency, when ionophores are used, is due to a shift in volatile fatty acid ratios and production in the rumen, thus altering ruminant metabolism. Propionic acid production is increased over butyric and acetic acids, but there is no change in the total volatile fatty acid production. The amount of bacterial ammonia fixation is decreased, affecting ammonia digestion and rumen protein degradation.

Nitrogen retention and absorption are increased, and ruminal methane production is decreased.

Their role as a growth promoter

Monensin, one type of ionophore, has the potential to decrease dry matter intake (DMI) by 3.1-6.4% and increased average daily gain (ADG) by 1.6-2.5% in feedlot cattle, as well as increase feed efficiency by 1.3%. The potential of inclusion in forage or grain-based diets is a beneficial management technique to optimize the efficiency and performance of beef production systems. Beef producers, however, need to consider all the differences and particularities of each ionophore to make an informed and applicable decision for their system.

 

In feedlot diets, containing a high concentration of readily fermentable carbohydrates, ionophores generally influence feed efficiency by maintaining body weight gain and reducing feed intake. Forage-based diets including ionophores increase body weight gain and feed efficiency, but with increased feed intake. Forage quality consumed by cattle, impacting the passage rate and gut fill, and consequently intake response, will cause variation in the effect of ionophores on intake.

 

These effects on ruminant metabolism are partially due to the effect of ionophores on ruminal microbiota and fermentation routes. Approximately 75 to 85% of energy derived from the diet is converted to ruminal VFA (Volatile Fatty Acids), the remaining energy being lost as heat and methane. The predominant VFA in the rumen are acetate, propionate, and butyrate, where their proportions are widely influenced by diet composition. In a forage-based diet, the proportions of acetate, propionate, and butyrate are generally 70:20:10. With a grain-based diet, the proportion is generally 50:40:10.

 

Ruminal fermentation routes, VFA, and methane production.

All VFA are vital in energy provision for the ruminant, but propionate is the only one acting as a precursor for glucose synthesis. Propionate represents 27% to 54% of the total glucose synthesized by the liver. Propionate also acts as a hydrogen sink, but acetate and butyrate are hydrogen sources, and hydrogen is the major substrate for methane formation. Methane is a major source of energy loss, ranging from 2% to 12% of gross energy intake. By being able to manipulate VFA production to increase propionate, there will be greater feed energy utilization and performance of the animal. Additionally, there will be a mitigation of methane production, thus decreasing the loss of energy. Ionophores inhibit methanogenesis by decreasing the availability of the substrates needed by methanogenic bacteria - hydrogen and formate.

 

When methanogenesis is decreased, propionate increases at the expense of acetate. Because propionate can be oxidized by the animal, more feed energy can be used for production and growth. The type of diet as well as the aim of production greatly influences the choice of ionophore to be used as well as how to use it.

 

Nitrogen metabolism effects

 

Ruminal microorganisms ferment most of the protein from the diet to VFA and ammonia. Ammonia can easily accumulate due to the inefficiency of degrading proteins and amino acids in the rumen, as ruminal ammonia production often exceeds the capacity of ammonia-utilizing species. This causes a loss of dietary nitrogen. The excess ammonia is converted to urea by the liver and can be recycled back to the rumen or lost in urine. 

 

Monensin has a ‘protein-sparing’ effect through decreasing ammonia production: ionophores can reduce ruminal proteolysis and inhibit deamination. Therefore, a greater amount of nitrogen reaches the abomasum from the diet instead of being lost in urine as urea. 

 

Peptostreptococcus and Clostridium are gram-positive bacteria that have the ability to produce high concentrations of ammonia in the rumen. They require amino acid sources for growth, thus their inhibition will reduce deamination of dietary proteins. The increased availability of the peptides and ammonia will stimulate the growth of rumen bacteria.

 

The dangers and limitations

Cattle are not as sensitive to the adverse effects of ionophores as other species, such as horses. This could be due to ruminal breakdown, decreased absorption, increased first pass effect by the liver, or differences in cell wall structure, resulting in reduced cellular uptake. Their risk, however, is partially eliminated. Clinical symptoms of ionophore toxicosis in cattle vary from decreased feed intake to severe heart and skeletal muscle damage. Intravenous monensin caused ataxia, hyperpnea, polyuria, and anorexia. Lasalocid- and monensin-poisoned steers developed anorexia, tachycardia, hyperventilation, dyspnea, watery diarrhea, muscle tremors, weakness, and incoordination. Mis-mixing and dosage errors are the leading causes of ionophore toxicosis.

 

There is no specific treatment for ionophore toxicosis. General supportive care can be attempted, but deaths can be seen long after exposure has stopped, along with permanent heart damage. Antibiotic resistance is a constant concern. Despite growing concern about Gram-positive bacteria becoming adapted and developing insensitivity to ionophores, there is limited evidence supporting this theory.

 

The improvement in feed efficiency resulting from ionophores decreased from 8.1% to 3.5% over the past 50 years, but this is not necessarily due to resistance. Rather, it is a consequence of enhanced management, nutrition, and health of feedlot cattle.

Ionophores are tools, and they are to be used as such. Farmers need to take their vision into account when considering the benefits of the different ionophores. They help adjust the microbial population of the rumen, thus modifying metabolism and reducing wastage. When used carefully, they will have a direct influence on feedlot efficiency and cattle performance.

 

References

Ensley, Steve. 2020. Ionophore Use and Toxicosis in Cattle. The Veterinary Clinics of North America. Food Animal Practice 36 (3): 641–52. doi:10.1016/j.cvfa.2020.07.001.

Rodrigo da Silva Marques, and Reinaldo Fernandes Cooke. 2021. Effects of Ionophores on Ruminal Function of Beef Cattle 11 (2871): 2871–71. doi:10.3390/ani11102871.

Russell, J.B. and Strobel, H., 1989. Effect of ionophores on ruminal fermentation. Applied and environmental microbiology, 55(1), pp.1-6. doi:10.1128/aem.55.1.1-6.1989.

Thompson, A J, Z K F Smith, M J Corbin, L B Harper, and B J Johnson. 2016. Ionophore Strategy Affects Growth Performance and Carcass Characteristics in Feedlot Steers. Journal of Animal Science 94 (12): 5341–49. doi:10.2527/jas.2016-0841.