Jackman et al. Journal of Animal Science and Biotechnology (2020) 11:44 https://doi.org/10.1186/s40104-020-00446-1 REVIEW Open Access Medium-chain fatty acids and monoglycerides as feed additives for pig production: towards gut health improvement and feed pathogen mitigation Joshua A. Jackman1*, R. Dean Boyd2,3 and Charles C. Elrod4,5* Abstract Ongoing challenges in the swine industry, such as reduced access to antibiotics and virus outbreaks (e.g., porcine epidemic diarrhea virus, African swine fever virus), have prompted calls for innovative feed additives to support pig production. Medium-chain fatty acids (MCFAs) and monoglycerides have emerged as a potential option due to key molecular features and versatile functions, including inhibitory activity against viral and bacterial pathogens. In this review, we summarize recent studies examining the potential of MCFAs and monoglycerides as feed additives to improve pig gut health and to mitigate feed pathogens. The molecular properties and biological functions of MCFAs and monoglycerides are first introduced along with an overview of intervention needs at different stages of pig production. The latest progress in testing MCFAs and monoglycerides as feed additives in pig diets is then presented, and their effects on a wide range of production issues, such as growth performance, pathogenic infections, and gut health, are covered. The utilization of MCFAs and monoglycerides together with other feed additives such as organic acids and probiotics is also described, along with advances in molecular encapsulation and delivery strategies. Finally, we discuss how MCFAs and monoglycerides demonstrate potential for feed pathogen mitigation to curb disease transmission. Looking forward, we envision that MCFAs and monoglycerides may become an important class of feed additives in pig production for gut health improvement and feed pathogen mitigation. Keywords: Antibiotics, Feed pathogen mitigation, Growth promotion, Gut health, Immune enhancement, MCFA, Medium-chain fatty acids, Monoglycerides Introduction have distinct targeting spectrums and potencies [2]. Certain Antibiotics have long been used in the swine industry for antibiotics have also been and continue to be used for treat- therapeutic purposes, as they are in human medicine, to ing subclinical diseases [3], and successful intervention can prevent severe clinical disease and death [1]. Antibiotics indirectly improve pig growth and feed efficiency [4]. work against bacteria and different classes of antibiotics Mechanistically, antibiotics can affect bacterial cell integrity and reproduction, and thus exert growth-promoting effects * Correspondence: [email protected]; [email protected] by modulating the composition of bacterial populations 1School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, within the pig gastrointestinal tract while reducing bacterial Republic of Korea pathogen levels throughout the body to prevent disease. 4Natural Biologics Inc., Newfield, NY 14867, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Jackman et al. Journal of Animal Science and Biotechnology (2020) 11:44 Page 2 of 15 Despite these important capabilities, there are mount- as health-promoting feed additives and feed pathogen ing concerns that antibiotic usage in food animals is mitigation agents for pig production. This article extends contributing to the global problem of antibiotic-resistant beyond previous reviews that broadly surveyed the bacteria across human and animal populations [5]. health-promoting effects of different types of fatty acids These concerns have led to calls to significantly reduce [19, 20], while providing more recent and deeper cover- or stop the use of antibiotics in animals that are also age of the chemical properties, pathogen disruption used in human medicine, particularly in cases where mechanisms, and field tests of MCFAs and monoglycer- they are used at sub-therapeutic levels to promote ides; the latter being an important class of MCFA deriv- growth [6]. Legislative bans on growth-promoting antibi- atives that has not been reviewed before [21, 22]. In otics have been passed in different parts of the world, addition, we provide coverage of MCFAs and monoglyc- such as the European Union [7], while other regulatory erides as feed pathogen mitigation agents and discuss actions, such as the revised Veterinary Feed Directive in current progress to inhibit high-priority viruses in feed, the United States, are encouraging more judicious use of which is significant because feed can be an important human medically relevant, therapeutic antibiotics in food vector for transboundary diseases [23]. We also address animal production, including halting sub-therapeutic MCFA and monoglyceride encapsulation and delivery in usage of such antibiotics [8]. At the same time, discus- a variety of formats that may be useful for feed pathogen sion has been raised about how curtailing the use of mitigation, for enteric pathogen mitigation, and for de- growth-promoting antibiotics that act as prophylactics livery to distant enteric sites. to inhibit bacterial pathogens at the subclinical level could lead to the increased use of therapeutic antibiotics Medium-chain fatty acids and monoglycerides among pigs displaying clinical infections [9]. MCFAs (defined as saturated fatty acids with C6 to C12 Concerns and legislative actions around antibiotic use hydrocarbon chains) and their corresponding monoglyc- in food animals are leading to an increase in the search eride derivatives are single-chain lipid amphiphiles. An for tools to counter pathogens. Promoting immune de- overview of the basic physical properties of important velopment or expression in young animals is one ex- MCFAs and monoglycerides is presented in Table 1. ample, which also tends to improve growth [10]. A MCFAs and monoglycerides are naturally present in recent addition to vaccines, therapeutic drugs, and the milk produced by some animals [24] as well as in immune enhancers is medium-chain fatty acids other natural sources such as coconut oil [25]. They are (MCFAs), especially saturated MCFAs with 6–12 building blocks of MCTs, which can be used as feed ad- carbon-long chains, which have demonstrated positive ditives and lipases break down the triglycerides in vivo benefits as feed additives by improving animal health, to yield MCFAs and monoglycerides among various hy- production, and feed digestibility [11]. These efforts drolysis products [13, 15]. The MCT approach is useful have built on pioneering works that utilized medium- because, unlike certain MCFAs, they do not have ad- chain triglycerides (MCTs) as feed additives in verse odors and facilitate digestion and release of conjunction with lipolytic enzymes, called lipases, that MCFAs and monoglycerides in the stomach along with can catalyze in vivo MCT hydrolysis and subsequent progressive release in the foregut as well. Depending on release of biologically active MCFAs and monoglycer- the situation, the MCTs may be delivered as a standa- ide derivatives to support pig growth and develop- lone feed additive if the feed source contains endogen- ment [12–15]. Importantly, free MCFAs and ous lipases or if gastric lipase secretion in the pig is monoglycerides also exhibit antiviral and antibacterial sufficiently developed, or can be delivered together with activity [16, 17]. The combined health-promoting and an exogenous lipase [14]. pathogen-mitigating functions of MCFAs and mono- Another option that is becoming popular and is the main glycerides are particularly significant in light of the focus of this review article involves directly using high-purity expanding African Swine Fever virus (ASFv) epidemic, formsofdesiredMCFAsand/ormonoglyceridesastheaddi- which highlights the devastation of, and urgency to tive, and to directly incorporate them into feed and/or water. address, virus outbreaks in the swine industry [18]. An important benefit of directly using free MCFAs and/or Over the past few years, there has been progress in evalu- monoglycerides in feed is that they exhibit antimicrobial ating the performance of free MCFAs and monoglycerides properties and thus can potentially inhibit viral and bacterial as feed additives in pig diets as well as in understanding pathogens in the feed to reduce the risk of disease transmis- mechanistic aspects of how these compounds function. sion. Of note, depending on the jurisdiction,