Avian influenza, also known as bird flu, is a viral infection that primarily affects birds, including layer hens. The most common and well-known strain of avian influenza is caused by influenza A subtype H5N1. The avian influenza virus can cause a range of symptoms in infected birds, depending on the strain and the severity of the infection and the severity of an outbreak can vary among different strains of the virus. Some strains may cause mild illness, while others can be highly pathogenic and result in significant mortality rates among infected birds. The virus primarily targets the respiratory and digestive systems in birds, but it can also affect other organs. In severe cases of avian influenza, the virus can lead to systemic infections and damage multiple organs, including the liver.
The avian influenza virus can cause inflammation and lesions in the liver. The severity of liver involvement in combating the virus may vary depending on factors such as the strain of the virus, the age and species of the bird, and the presence of any pre-existing health conditions. The virus can lead to degeneration and even necrosis (cell death) of liver cells. Liver damage in birds infected with avian influenza is often a result of the body’s immune response to the virus. The liver plays a crucial role in the immune response and detoxification processes in the body, so any damage to the liver can have broader health implications for the infected bird.
The liver is involved in the synthesis of acute-phase proteins (macrophages) via the Kupffer cells, which are part of the innate immune response. These macrophages help recognise and eliminate pathogens, including viruses, and their production is often upregulated in response to infection. The liver also produces interferons, which are signalling proteins that help neighbouring cells resist viral replication. The liver is responsible for detoxifying harmful substances. During a viral infection, it may encounter increased levels of toxins or metabolic byproducts. The liver plays a central role in regulating metabolism and energy balance. During a viral infection, the chicken’s metabolism may be altered, and the liver helps to ensure a proper energy supply for the immune response. It may mobilise energy reserves and modulate metabolic pathways to support the chicken’s overall health. While the primary site for antibody production is the spleen and other lymphoid tissues, the liver can also contribute to the production of antibodies during an immune response. Maintaining optimal liver function is crucial for the overall health of the chicken and its ability to cope with the additional stress imposed by the viral infection.
Control measures such as quarantine, culling infected birds, and implementing biosecurity measures are commonly employed to reduce the risk of transmission and prevent the spread of avian influenza among poultry populations. Feed additives can also be added to the diet to help support the liver, both during an infection and also post-infection when the bird is recovering. One such feed additive is betaine, which can play a significant role in supporting the liver in fighting possible infections as well as in alleviating liver damage in chickens.
All about betaine
Betaine is composed of three methyl groups with a hydrophobic nature and one carboxyl group with a hydrophilic nature. Acute or chronic liver injuries, dysfunction, and failure could be mediated via either the direct effect of betaine on the mitochondria that alleviate oxidative stress or via the inhibition of satellite cell activities.
The mechanism of betaine in poultry liver injuries (adapted from Abd El-Ghany & Babazadeh, 2022).
Betaine reverses inflammation
Betaine is believed to reverse inflammation and the accumulation of fat and connective tissue by several mechanisms:
- acting as a methyl donor for the conversion of homocysteine to methionine when methionine synthetase activity is inhibited;
- methylating phospholipids via the Kennedy pathway (an important route in the synthesis of very low-density lipoproteins prior to hepatic export); and
- restoration of liver mitochondrial glutathione and S-adenosyl methionine (SAM):S-adenosyl homocysteine ratios, which reduces hepatic oxidative stress.
Betaine improves liver function
Betaine can improve liver functions as it acts as a methyl donor in various metabolic processes, including the methionine cycle, which plays a crucial role in liver function. Methionine is an essential amino acid that plays a role in various physiological processes, including protein synthesis and liver function. Betaine donates the methyl radicals for the remethylation of homocysteine to methionine and to formulate creatine, carnitine, and phosphatidylcholine through the S-adenosyl methionine pathway. By donating methyl groups, betaine helps in the synthesis of phosphatidylcholine, an essential component of cell membranes, and aids in the breakdown of homocysteine, reducing its toxicity to the liver.
Betaine regulates lipid metabolism
In the liver, betaine significantly affects lipid metabolism through synthesising carnitine and creatine in the muscles and liver of chickens. It reduces the accumulation of fat in the liver (hepatic steatosis) by promoting the export of triglycerides from the liver. This is important in preventing and treating fatty liver disease in laying hens. Creatine is active in the muscle energy buffering system. Also known as methyl guanidine acetic acid, creatine is a nitrogen-containing chemical substance synthesised in the brain, kidney, pancreas, and liver, as a precursor for arginine, methionine, and glycine. Creatine regulates cellular energy metabolism due to its role as a phosphate carrier and reservoir for adenosine triphosphate (ATP) synthesis.
Betaine as an antioxidant
Betaine has antioxidant properties that protect liver cells from oxidative stress and damage. Betaine was found to exert its antioxidant activity via two mechanisms. One mechanism involves scavenging cellular reactive oxygen species (ROS) generation in cells via upregulation of endogenous nonenzymatic antioxidant defences. The other inhibits ROS generation by isolating cells from the oxidative stress inducer. It can help neutralise harmful free radicals, reducing inflammation and oxidative damage to the liver. Oxidative stress can negatively impact the liver, and antioxidants play a role in protecting the liver from such damage.
Betaine regulates the inflammatory response
The osmo-regulatory effect of betaine is vital for the immune system. Inflammation is a key component of the immune system’s defence mechanisms. By regulating the inflammatory response, betaine could potentially help poultry maintain a balanced immune response. Betaine can support the immune system in laying hens, helping to reduce susceptibility to infections and diseases that may affect the liver.
Betaine does it all
In conclusion, the incorporation of betaine into layer diets emerges as a promising strategy to enhance liver function and overcome possible liver damage caused during the exposure to the avian influenza virus. By supporting liver functions during challenging times, the hens could get back to optimal egg production and quality sooner. As the poultry industry seeks sustainable and effective solutions to optimise production outcomes post-exposure to avian influenza, the inclusion of betaine in layer diets represents a valuable avenue for improving liver function and overall well-being in laying hens.