The lipopolysaccharide content of the gut increases during acidosis and managing diets to reduce clinical and subclinical acidosis is beneficial. Increasing fibre content and reducing easily fermentable carbohydrates can reduce the likelihood of excess short-chain fatty acids or, in the case of clinical acidosis, lactic acid. However, energy requirements to maximise milk or muscle production may limit the extent to which diet manipulation can be employed.
Technical Business Manager – North America
Volac
The body has several physical barriers against “external” threats, including the skin, the respiratory linings, and the digestive tract. Of these three, the digestive tract faces the most potential threats, not only from ingested substances but also from what develops in situ, such as the growth of micro-organisms, the toxins they produce, and even the remnants of those that die within the tract. Both non-pathogenic and pathogenic bacteria commonly reside within the Gastrointestinal (GI) tract, with species like Salmonella and E. coli being typical examples of Gram-negative (G-) bacteria. This means that their cell walls do not retain the dye used during Gram staining. When Gram-negative bacteria lyse (both pathogenic and non-pathogenic), their cell walls break into segments that contain “endotoxins” composed of Lipopolysaccharides (LPS). Unfortunately, these LPS are highly reactive and send strong signals to the immune system, resulting in a pronounced inflammatory response. Lipopolysaccharides bind to TLR4 receptor sites, triggering a cascade of reactions that culminate in the production of pro-inflammatory cytokines. Furthermore, the absorption of LPS has been shown to reduce feed intake, exacerbating the issue, as animals experience increased energy requirements while available dietary energy decreases, leading to the utilisation of body lipids and a potential decline in body proteins.
When the digestive tract is in a state of healthy homeostasis, the number of bacteria is kept “in check” and the host is able to cope with the endotoxins produced (due to natural bacterial cell death). However, disturbances in the diet or the diet itself can stimulate bacterial growth. Conditions such as subclinical and clinical acidosis can also cause excess death and lysis of bacteria. Diet composition can influence absorption; for instance, the lipid portion of LPS can combine with dietary fats, leading to increased absorption (Kelly et al., 2012). Additionally, factors such as heat stress and certain mycotoxins can weaken the cell-to-cell connections and the integrity of the gut, allowing greater absorption of LPS present in the digestive tract.
Aside from its role in inflammation, LPS also has effects that can exacerbate or increase the risk of other metabolic diseases. Dairy cows infused with LPS show dose-dependent reductions in serum calcium concentrations (Waldron et al., 2003). Elevated plasma LPS concentrations are associated with a decrease in blood calcium and magnesium due to an increase in IL-1β (Gray et al., 2007), which may contribute to milk fever.
LPS can also impact lipid metabolism. Research by Chirivi et al. (2022) demonstrated that LPS can reduce the antilipolytic effects of insulin, leading to dysregulation of lipolysis. This is particularly important for transition cows that require effective regulation of fat release and storage due to general negative energy balance and potential declines in liver function.
HOW CAN THE LPS THREAT BE REDUCED?
The lipopolysaccharide content of the gut increases during acidosis and managing diets to reduce clinical and subclinical acidosis is beneficial. Increasing fibre content and reducing easily fermentable carbohydrates can reduce the likelihood of excess short-chain fatty acids or, in the case of clinical acidosis, lactic acid. However, energy requirements to maximise milk or muscle production may limit the extent to which diet manipulation can be employed. Including buffers and certain yeast products can help mitigate acidosis and increase rumen pH. Yeast can compete for soluble carbohydrates that could otherwise be used by Streptococcus bovis and Lactobacillus to produce lactic acid; additionally, yeast may encourage the growth of Megasphaera eldenii, which can convert lactic acid into butyric acid (Amin and Mao, 2021).
Feed additives can also be used to reduce the growth of Gram-negative (-) bacteria, such as E. coli and Salmonella species. Yeast cell wall products have demonstrated an ability to bind live bacteria, thereby reducing their ability to grow and reproduce. Feeding fructo-oligosaccharides supports the growth of probiotic or beneficial bacteria, which can reduce pathogenic bacterial growth by controlling the micro-environment around the microvilli through competitive inhibition.
The growth of Gram-negative bacteria and subsequent LPS production can never be entirely eliminated. However, the effects of LPS can be mitigated through feed ingredients that help maintain healthy homeostasis, support the growth of probiotic bacteria, and promote intestinal integrity, thereby limiting the growth and prevalence of harmful bacteria. Additionally, specific inorganic compounds (such as aluminosilicates) and organic compounds (such as components of yeast cell walls) can bind LPS, preventing both their absorption and their ability to stimulate inflammation.
Although LPS presents a genuine threat to animal production, their effects can be mitigated using specific feed additives and practical management strategies to reduce the associated risks.
References
1. Ametaj, B. N., Q. Zebeli, and S. Iqbal. 2010. Nutrition, microbiota, and endotoxin-related diseases in dairy cows. Rev. Bras. Zootec. 39:433–444.
2. Amin, A.A. and S. Mao. 2021. Influence of yeast on rumen fermentation, growth performance and quality of products in ruminant: A review. Animal Nutrition. 7:31-41
3. Eckel, E.F. and B. N. Ametaj. 2016. Role of bacterial endotoxins in the etiopathogenesis of periparturient diseases of transition dairy cows. J. Dairy Sci. 99: 5967-5990.
4. Gray, C. P., T. D. St George, and N. N. Jonsson. 2007. Milk fever in dairy cattle: A novel hypothesis for immune mediated etiology. Cattle Pract. 15:277–282.
5. Waldron, M. R., B. J. Nonnecke, T. Nishida, R. L. Horst, and T. R. Overton. 2003. Effect of lipopolysaccharide infusion on serum micromineral and vitamin D concentrations in dairy cows. J. Dairy
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7. Chirivi, M., C.J. Rendon, M.N. Myers, C.M. Prom, S. Roy, A. Sen, A.L. Lock and G. A. Conteras. 2022. Lipopolysaccharide induces lipolysis and insulin resistance in adipose tissue from dairy cows. J. Dairy Sci. 105:842-855.
8. Maeshima, N., and R.C. Fernández. 2013. Recognition of Lipid A variants by the TLR$-MD-2 receptor complex. Cellular and Infection Microbiology. 3: Article 3.
9. Nova, Z. H. Skovierova and A. Calkovska. 2019. Alveolar-Capillary Membrane-Related Pulmonary Cells as a Target in Endotoxin-Induce Acute Lung Injury. Int. J. Molecular Sciences. 20: 831.
10. Kelly, C. J., S. P.Colgan, and D.N. Frank. 2012. Of microbes and meals: the health consequences of dietary endotoxemia. Nutr Clin Pract 27, 215–225.
About Bryan Miller
Bryan Miller has been in the feed industry for over 35 years in feed mill management, product development (including authoring patents) and technical services. For most of the past 10 years he has focused on gut and liver health, including mycotoxin remediation.
