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Frequently Asked Questions (FAQ) TABLE of CONTENTS Optimizing gut health by neutralizing ß-mannans in feed ingredients. HemicellTM is a highly specific, patented enzyme for animal diets. Its mode of action helps support animal performance by mitigating an innate immune response caused by ß-mannans found in feed ingredients. 1-5, 11, 14 With fewer ß-mannans in the feed, an innate immune response is avoided; thereby optimizing nutrients to be used for performance, reproduction, and health. 2, 4, 6 Frequently Asked Questions (FAQ) TABLE OF CONTENTS 1 Enzyme basics 2 ß-mannans and FIIR 3 Hemicell and its Mode of Action 4 Effects of Hemicell 5 Use of Hemicell 6 Engineering 7 Glossary of terms 8 References Please direct additional questions to your Elanco representative. 1 Enzyme basics What are enzymes? Enzyme basics 1 Enzymes are proteins, which are organic compounds. Like all organic compounds, enzymes are sensitive to temperature and pH. Once they have done their job, enzymes completely break down into amino acids and peptides that are either metabolized or excreted. Enzymes act as ß-mannans and FIIR 2 catalysts for many biochemical processes in the body, from digestion to tissue regeneration. Without enzymes, such reactions would likely not take place at a metabolically useful rate. Hemicell and its 3 Mode of Action How do enzymes work? Enzymes are very selective and each catalyzes one specific reaction. The molecules each enzyme can react with are referred to as substrates. Only substrates (or molecules) with exactly Effects of Hemicell 4 the right shape (chemical bonds) can bind to an enzyme and react. Once bound, the enzyme breaks down the substrate into component parts which the animal can absorb. Consider lactose (found in milk) as an example. A specific enzyme (lactase) binds with the substrate (lactose), 5 Use of Hemicell breaking it into two simple sugars (galactose and glucose) that the animal is able to absorb. What is the difference between exogenous and endogenous enzymes? 6 Engineering Endogenous enzymes are produced by the animal itself; exogenous enzymes (e.g., Hemicell) are not produced by the animal so they must be supplied via the diet. 7 Glossary of terms 8 References Please direct additional questions to your Elanco representative. 2 ß-mannans and FIIR What is a ß-mannan? Enzyme basics 1 ß-mannan is an anti-nutritive fibre found in common feed ingredients. It is a high molecular weight molecule – technically, a long chain of mannose sugar units with galactose side chains, unable to be naturally broken down in the bird or pig’s digestive system. (See figure 1).6 2 ß-mannans and FIIR CH OH CH OH CH2OH 2 2 OH OH O OH O O OH OH OH Hemicell and its OH O 3 Mode of Action OH O OH O CH OH CH CH OH CH OH CH CH2OH CH2OH CH2 2 CH2OH 2 2 2 2 O O O O O O O O O OH OH OH OH OH OH O OH OH O OH OH O OH OH O OH OH O OH OH O OH OH O O O Effects of Hemicell 4 Figure 1. Legume galactomannan What feedstuffs contain ß-mannans and how much do they contain? 5 Use of Hemicell Most vegetable feed ingredients contain ß-mannans. Soybean meal, sunflower meal, rapeseed and copra meal are common ß-mannan sources in poultry and swine diets across the globe. Estimated levels of soluble ß-mannans in common ingredients are presented in table 1. 6 Engineering Do ß-mannans affect Intestinal Integrity? Yes, they may reduce Intestinal Integrity and increase the impact of infections.29, 32 7 Glossary of terms Why do ß-mannans affect performance? Mannose sugars (found in the backbone of ß-mannans) are found in different molecular 8 References configurations on many pathogens.6, 11 This likely explains why mannose is one of the important PAMP (Pathogen Associated Molecular Patterns) molecules that triggers an innate immune Table 1: Estimated ß-mannan content* 20, 30 β-mannans, Ingredient Pct., as is1 Minimum Maximum Corn gluten meal 0.17 0.10 0.24 DDGS 0.57 0.23 1.09 Oats 0.31 – – Oats, dehulled 0.16 0.09 0.22 Palm kernel meal 7.24 5.34 10.90 Peas 0.11 0.09 0.12 Rapeseed meal 0.18 0.13 0.37 Rapeseed expeller 0.13 – – Rapeseed, whole 0.08 0.07 0.09 Soya hulls 6.67 6.43 6.91 Soybean meal 44% CP 0.79 0.38 1.30 Soybean meal 48% CP 0.59 0.28 1.00 Soybean meal, fermented 0.59 0.58 0.59 Soybean meal, Full Fat 0.71 0.42 1.05 Sunflower meal, ≤32% CP, w/ hulls 0.62 0.53 0.69 Sunflower meal, >32% CP, w/o hulls 0.57 0.42 0.75 Wheat 0.27 0.11 0.42 Wheat bran 0.25 0.21 0.34 1 Estimated Soluble β-mannan, % = Soluble mannose % x 1.5 Please direct additional questions to your Elanco representative. 2 ß-mannans and FIIR (cont.) response whenever they come into contact with immune receptors . Simply put, the immune Enzyme basics 1 system mistakes ß-mannans as an invading pathogen.6, 11, 17, 18 ß-mannan fibres “look like” a pathogen to the immune system, and will therefore trigger the cascade of events designed to protect the animal against infections. This type of immune response can have a negative 2 ß-mannans and FIIR impact on animal health and performance, as it typically consumes energy and other valuable nutrients..1-4, 6, 28 Hemicell and its Recognition of ß-mannans by the innate immune system triggers a cascade of events: 3 Mode of Action • Critical resources (energy and nutrients) that otherwise would be used for production, growth or health are diverted in favor of immune defense mechanisms. This unnecessary diversion leads to reduced efficiency and higher production costs.1-5 Effects of Hemicell 4 • Lowers plasma glucose and insulin secretion7, 8, 16 • Reduces water absorption9, 10 • Reduces nitrogen retention4, 17 5 Use of Hemicell What is FIIR? FIIR is an acronym for Feed-Induced Immune Response. It’s a name for the innate immune 6 Engineering response that is triggered when a substance, such as D-mannose, is recognized by the innate immune system as being pathogen-like. This recognition is due to these compounds having similar molecular patterns as pathogens, hence they are referred to as PAMPs or Pathogen 7 Glossary of terms Associated Molecular Patterns. The result is that the innate immune system recognizes these PAMPs and initates a counter-response requiring diversion of nutrients from productive purposes to fuel this response.6, 11-14, 31 References 8 Is it possible to prevent FIIR from ß-mannans without adding ß-mannanase to the feed? Hemicell is the most cost effective means to prevent FIIR from ß-mannans. Genetic improvement to reduce the ß-mannan content in soy may also be possible but our analysis of commercial soybean meal samples does not support this. 20, 30 Does the effect of soluble ß-mannans depend on the source? The soluble ß-mannan content in the feed (often referred to as ß-galactomannans) is the most important because soluble ß-mannans are much more likely to come in contact with immune receptors and provoke an innate response. The source of the soluble ß-mannans is unlikely to affect their influence on FIIR or animal performance because it is the mannose sugar molecules that are recognized by the innate immune system.3, 11, 14 Please direct additional questions to your Elanco representative. Hemicell and its 3 Mode of Action What is Hemicell? Enzyme basics 1 Hemicell is a patented enzyme produced by fermentation of Paenibacillus lentus, (formerly known as Bacillus lentus), and the active ingredient is endo-1,4-ß-D-mannanase. The ß-mannanase enzyme degrades soluble ß-mannan fibres, mainly ß-galactomannan and ß-mannans and FIIR 2 ß-glucomannan. Hemicell and its What’s different about Hemicell compared to other enzymes? 3 Mode of Action Most feed enzyme products are nutrient releasing enzymes, which break down substrate in the feed to make more nutrients and energy available for growth and production. Hemicell is 4 Effects of Hemicell a nutrient-sparing enzyme that optimizes gut health by neutralizing ß-mannans found in most vegetable feedstuffs (see Table 1) that trigger a Feed-Induced Immune Response (FIIR). By degrading these fibres, Hemicell reduces the nutrient waste and performance losses from 6-11, 31 5 Use of Hemicell the futile innate immune response to ß-mannans. How much substrate does Hemicell need to be effective? 6 Engineering Use of Hemicell to reduce unnecessary immune activity from ß-mannans is expected to be cost effective in diets with at least 0.2% soluble ß-mannans. Glossary of terms 7 If the ß-mannan content is so low, why should I use an enzyme? Very little ß-mannan is actually needed (0.20%) to trigger the innate immune response and 8 References because ß-mannans are found in all vegetable feed ingredients. The mannan oligosaccharide fragments that are produced when Hemicell hydrolyses ß-mannans are too small to be recognized by the innate immune system. Reducing the Feed- Induced Immune Response (FIIR) from ß-mannans helps spare valuable energy nutrients, which can be re-directed toward growth and performance. Does the value of Hemicell increase in diets with high ß-mannan content? Yes, there are titration data to demonstrate this.6, 18 What differentiates Hemicell from cocktail enzymes with ß-mannanase on the label? Hemicell is a patented enzyme product with a guaranteed minimum ß-mannanase activity.
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