Novel and disruptive biological strategies for resolving gut health challenges in monogastric food animal production

Use of feed antibiotics as growth promoters for control of pathogens associated with monogastric food animal morbidity and mortality has contributed to the development of antimicrobial resistance, which has now become a threat to public health on a global scale. Presently, a number of alternative feed additives have been developed and are divided into two major categories, including 1) the ones that are supposed to directly and indirectly control pathogenic bacterial proliferation; and 2) the other ones that are intended to up-regulate host gut mucosal trophic growth, whole body growth performance and active immunity. A thorough review of literature reports reveal that efficacy responses of current alternative feed additives in replacing feed antibiotics to improve performances and gut health are generally inconsistent dependent upon experimental conditions. Current alternative feed additives typically have no direct detoxification effects on endotoxin lipopolysaccharides(LPS) and this is likely the major reason that their effects are limited. It is now understood that pathogenic bacteria mediate their negative effects largely through LPS interactions with toll-like receptor 4, causing immune responses and infectious diseases. Therefore, disruptive biological strategies and a novel and new generation of feed additives need to be developed to replace feed antibiotic growth promoters and to directly and effectively detoxify the endotoxin LPS and improve gut health and performance in monogastric food animals.     

丁酸对肠道健康的影响及作用机制的研究进展

丁酸是一种主要的短链脂肪酸,通常作为饲料添加剂来替代抗生素,以提高动物生长性能。文章综述了丁酸及其盐通过促进肠道健康来发挥促生长作用的可能机制,包括肠道黏膜结构、酶活性、肠道菌群、肠道免疫系统以及减轻动物氧化应激等方面。     

Strategies to modulate the intestinal microbiota and their effects on nutrient utilization,performance, and health of poultry

Poultry is widely produced and consumed meat global y. Its demand is expected to continue increasing to meet the animal protein requirement for ever-increasing human population. Thus, the chal enge that poultry scientists and industry face are to produce sufficient amount of poultry meat in the most efficient way. In the past, using antibiotics to promote the growth of poultry and manage gut microbiota was a norm. However, due to concerns over potential fatalistic impacts on food animals and indirectly to humans, their use as feed additives are banned or regulated in several jurisdictions. In this changed context, several alternative strategies have been proposed with some success that mimics the functions of antibiotics as growth promoters and modulate gut microbiota for their beneficial roles. These include the use of probiotics, prebiotics, organic acids, and exogenous enzyme, among others. Gut microbiota and their metabolic products improve nutrient digestion, absorption, metabolism, and overal health and growth performance of poultry. This paper reviews the available information on the effect of feed additives used to modulate intestinal microbiota of poultry and their effects on overal health and growth performance. Understanding these functions and interactions wil help to develop new dietary and managerial strategies that wil ultimately lead to enhanced feed utilization and improved growth performance of poultry. This review wil help future researchers and industry to identify alternative feed ingredients having properties like prebiotics, probiotics, organic acids, and exogenous enzymes.     

"肺肠同制"思路对饲料替抗的启示

目前养猪业的饲料替抗方向大多专注于猪只肠道,主要针对肠道抗菌、抑菌、免疫调节、菌群调理和消化率提升等方面进行研究与尝试,往往忽略了肠道与肺部之间的关联性。替抗的本质是通过调节健康、调理代谢来改善猪只的生产性能。文章主要从三个方面阐述了肠道与肺部的关系,即肺部供氧状态与肠道结构功能之间的关系,肠道菌群平衡、肠道代谢产物变化与肺部功能之间的关系以及两者之间神经联系等,并提出"肺肠同制"理念,以期为替抗工作提供新思路。     

片球菌抑菌机制及其在畜禽生产中的应用

寻找抗生素替代品是养殖业面临的一大课题。片球菌（Pediococcus）是饲料添加目录中允许的益生菌之一,它是一种革兰氏阳性乳酸菌。大量研究表明,片球菌在食品、医疗和养殖行业中有着巨大的应用价值,它们在宿主肠道黏膜细胞表面具有的良好的定植能力,减少了其他细菌的黏附。同时,片球菌能够产生包括片球菌素、有机酸和过氧化氢在内的许多抗菌物质,因而在抑制病原菌生长、改善肠道微生物群落结构、刺激宿主免疫、促进养殖动物生产健康并提升动物生长性能等方面表现出良好的益生性能,但是相比较其他益生菌而言其关注程度不高。作者总结了片球菌产生抑菌物质的种类及其抑菌机制,介绍了片球菌的黏附和免疫调控作用方式,以及片球菌在猪和鸡等畜禽养殖动物生产上的应用,旨在为其在动物生产中的合理应用提供理论参考。片球菌具有广谱、稳定的抑菌效果,丰富的益生性能,它们有利于畜禽动物健康生长,预防病原菌感染,减少疾病发生,因此值得加大推广和应用的力度。     

Antibacterial Mechanism of Pediococcus and Its Application in Livestock and Poultry Production

Finding antibiotic alternatives is a major issue in the breeding industry.Pediococcus, a kind of Gram-positive lactic acid bacteria,is one of the probiotics allowed in the feed addition catalogue.A large number of studies have shown that Pediococcus has great application value in the food,medical and breeding industries.Their good colonization ability on the surface of the host intestinal mucosal cells reduces the adhesion of other bacteria.Meanwhile,Pediococcus is able to produce many antibacterial substances including pediocin,organic acids and hydrogen peroxide.Therefore,it's showing their good probiotic performance in inhibiting the growth of pathogenic bacteria,improving the intestinal microbial community structure,stimulating the host's immunity,promoting the health of farmed animals,and improving animal growth performance,However,compared with other probiotics,its degree of attention is not high.This article summarizes the types of bacteriostatic substances produced by Pediococcus and their bacteriostatic mechanisms,introduces Pediococcus's adhesion and immune regulation,and the application of Pediococcus in the production of animals such as pigs and chickens.The aim was to provide a theoretical reference for Pediococcus's reasonable application in animal production.The results discussed in this article indicated that Pediococcus had broad-spectrum,stable bacteriostatic effects and rich probiotic properties.It's beneficial to the healthy growth of livestock and poultry,prevents pathogenic bacterial infections,and reduces the incidence of diseases.Therefore,Pediococcus is worth increasing its promotion and application.     

An update on alternatives to antimicrobial growth promoters for broilers

Livestock performance and feed efficiency are closely interrelated with the qualitative and quantitative microbial load of the animal gut, the morphological structure of the intestinal wall and the activity of the immune system. Antimicrobial growth promoters have made a tremendous contribution to profitability in intensive husbandry, but as a consequence of the increasing concern about the potential for antibiotic resistant strains of bacteria, the European Commission decided to ban all commonly used feed antibiotics. There are a number of non-therapeutic alternatives, including enzymes, (in)organic acids, probiotics, prebiotics, etheric oils and immunostimulants. Their efficacy and mode of action are briefly described in this review.     

抗生素饲料添加剂在动物生产中的规范应用

抗生素等抗菌药物作为饲料添加剂在动物饲料中使用,促进动物生长及预防某些疾病,对饲料工业及畜牧业的发展做出了很大的贡献。但抗生素的使用也引发了许多严重的食品安全问题和环境污染,而已有的一些抗生素替代物效果不够确实和稳定,目前在我国的饲料生产中还是在大量的使用抗生素饲料添加剂。科学地认识和对待饲用抗生素,正视并重视抗生素的安全性问题,正确引导、规范和合理使用抗生素饲料添加剂是实现畜牧业健康发展的重要支撑。     

中链脂肪酸在仔猪营养中的生理功能研究进展

中链脂肪酸(MCFAs)由含有单羧酸的脂肪酸组成,6~12个碳原子不等,包括己酸(C6)、辛酸(C8)、癸酸(C10)和月桂酸(C12)。MCFAs可以通过胃黏膜被吸收,中链脂肪酸甘油三酯(MCTs)可以被完整地吸收进入肠上皮细胞,然后被微粒体脂肪酶水解。MCFAs是一种很容易获得的能量来源,不仅能够改善肠上皮黏膜结构,还因其能够穿透细菌的半透膜并破坏细胞内部结构而具有很强的抗菌活性。因此,MCFAs可以作为断奶仔猪饲料的良好补充剂,提高仔猪的生长性能,是一种潜在的饲料抗生素替代品。本文将从MCFAs对仔猪生长性能、肠道微生物平衡、肠道发育及免疫调节作用进行综述,为MCFAs在养猪业中的科学应用提供参考。     

Effects of Mannanoligosaccharide on Growth Performance,the Development of Gut Microflora,and Gut Function of Broiler Chickens Raised on New Litter

In search of substances to replace antibiotics as growth promoters for farm animals, mannanoligosaccharides (MOS) have been proposed as a possible alternative. In the present experiment, the influence of MOS on growth performance and bacteriological, morphological, and functional aspects of small intestine was investigated in broiler chickens at different ages. Three dietary treatments were used: a negative control without MOS or antibiotic, a positive control (Zn bacitracin), and 2 g of MOS/kg of diet. The MOS supplement tended to improve BW gain compared with the negative control in early life (P = 0.07). The counts of total anaerobic bacteria, lactic acid bacteria, and Clostridium perfringens were not affected by the supplementation of MOS. The counts of coliform bacteria were increased in young birds treated with MOS. No significant differences in the gut morphology and function were noticed between the MOS treatment and the negative or the positive control at d 14, but birds in the positive control group had significantly higher jejunal villi and mucosal alkaline phosphatase activities than MOS-supplemented birds at d 35. In the current study conducted under hygienic experimental conditions, the addition of MOS did not show a clear positive effect on performance or intestinal morphology and function.     

Effect of erythromycin on L-threonine transport in rabbit jejunum in vitro

Several antibiotics characterized by different molecular structures are known to affect some intestinal activities. Some of them have been described as inhibitors of the intestinal sugar and amino acid transport with different mechanisms. Erythromycin (EM) is a macrolide antibiotic acting as a motilin agonist and thus stimulating the gastrointestinal motor activity. Since several substances which increase the motor activity of the gastrointestinal tract may produce effects on the intestinal absorption of nutrients, the present study has been carried out to determine whether erythromycin affects the L-threonine intestinal absorption. The results obtained indicate that erythromycin diminishes the L-threonine intestinal transport, probably at the mucosal border level. Two groups of experiments carried out, with Na(+)-deprived medium and ouabain-enriched medium, might indicate that erythromycin action could be due to either a direct or an indirect action on the Na(+)-dependent L-threonine transport located in the brush border.     

Nutritional significance of amino acids,vitamins and minerals as nutraceuticals in poultry production and health – a comprehensive review

Nutraceuticals have gained immense importance in poultry science recently considering the nutritional and beneficial health effects of their constituents. Besides providing nutritional requirements to birds, nutraceuticals have beneficial pharmacological effects, for example, they help in establishing normal physiological health status, prevent diseases and thereby improve production performance. Nutraceuticals include amino acids, vitamins, minerals, enzymes, etc. which are important for preventing oxidative stress, regulating the immune response and maintaining normal physiological, biochemical and homeostatic mechanisms. Nutraceuticals help in supplying nutrients in balanced amounts for supporting the optimal growth performance in modern poultry flocks, and as a dietary supplement can reduce the use of antibiotics. The application of antibiotic growth enhancers in poultry leads to the propagation of antibiotic-resistant microbes and drug residues; therefore, they have been restricted in many countries. Thus, there is a demand for natural feed additives that lead to the same growth enhancement without affecting the health. Nutraceuticals substances have an essential role in the development of the animals’ normal physiological functions and in protecting them against infectious diseases. In this review, the uses of amino acids, vitamins and minerals as well as their mode of action in growth promotion and elevation of immune system are discussed.     

Feed supplemented with 3 different antibiotics improved food intake and decreased the activation of the humoral immune response in healthy weaned pigs but had differing effects on intestinal microbiota

The aim of this study was to determine the effects of 3 antibiotics used for pulmonary pathologies added in the feed of weaned pigs on growth performance, commensal microbiota, and immune response. At weaning, a total of 72 pigs were randomly assigned by BW and litter to 1 of the following diets: control (typical weaning diet), control + 400 mg of tilmicosin/kg, control + 600 mg of amoxicillin/kg, and control + 300 mg of doxycycline/kg. Individually penned pigs were slaughtered after 3 wk (12 pigs/treatment) or 4 wk (6 pigs/treatment). During the fourth week, all pigs received the control diet to test the residual effect of the antimicrobial supplementation. The antibiotic supplementation increased growth and feed intake during the first week (P < 0.01) and over the first 3 wk combined (P < 0.05). Gain-to-feed ratio tended to improve during the first week (P = 0.076) by the antibiotics compared with the control. Among the antibiotic treatments, no difference was observed in ADG and feed intake, which were also unchanged by the diet in the fourth week. The fecal enterobacteria counts were increased by amoxicillin on d 14 and 21 (P < 0.05 and 0.01, respectively) and were decreased by tilmicosin (P < 0.001) compared with the control. Amoxicillin decreased lactic acid bacteria (P < 0.01) counts compared with the control. The antibiotic supplementation tended to decrease total bacteria variability in the jejunum (Shannon index, P = 0.091) compared with the control. The antibiotic treatment decreased the mean total serum IgM concentration (P = 0.016) after 3 wk and did not change the mucosal histomorphometry of the small intestine. For tilmicosin, the observed positive action on piglet performance and feed intake can originate by the decreased costs of immune activation determined by the action on intestinal microbiota. For amoxicillin and doxycycline, the observation on intestinal and fecal microbiota seems to be not sufficient to explain their growth-promoting effect.     

乳酸杆菌在调节肠道屏障功能中的作用

乳酸杆菌不仅是动物肠道内存在的正常微生物,也是益生菌的重要组成部分。肠道屏障主要是由肠道黏膜免疫系统组成的免疫屏障、肠黏液层和肠上皮细胞层组成的肠黏膜物理屏障及肠道微生物构成的生物屏障构成。作者综述了近年来国内外有关乳酸杆菌制剂对肠道屏障功能调控作用的研究进展。     

Lectin binding profile of the small intestine of five-week-old pigs in response to the use of chlortetracycline as a growth promotant and under gnotobiotic conditions

Antibiotics have traditionally been used for growth promotion in the pork industry; however, their use in animal feed has recently been limited because of human health concerns. The intestinal microbiota plays an important role in mediating many physiological functions such as digestion and animal growth. It was hypothesized that use of antibiotics as growth promotants and subsequent variations in intestinal microbiota induce significant changes in the intestinal glycoconjugate composition, which ultimately affects animal growth and disease susceptibility. The aim of this study was to characterize the lectin binding profiles of the ileum of weanling pigs in response to the absence of intestinal microbiota and to the use of the antibiotic chlortetracycline as growth promotant. Eighteen half-sib piglets obtained by cesarean section were divided into 3 treatment groups (n = 6) and maintained as control, antibiotic-fed, and gnotobiotic piglets until 5 wk of age. The glycoconjugate composition of the ileal tissues was examined by lectin histochemistry. Lycopersicon esculentum lectin, Jacalin, Pisum sativum agglutinin, Lens culinaris agglutinin (LCA), and Sambucus nigra lectin showed significant differences (P < 0.05) in binding intensities on the dome and villous epithelium between the treatment groups. Griffonia simplicifolia lectin I, Glycine maxi agglutinin, and Arachis hypogea agglutinin exhibited differences (P < 0.05) between treatment groups in lectin binding on goblet cells. Triticum vulgaris agglutinin, Pisum sativum agglutinin, and LCA showed significant differences (P < 0.05) in binding intensities on dome, corona, and follicular regions of the ileum among treatment groups of animals. Overall, ileal tissues from gnotobiotic piglets expressed significantly weaker (P < 0.05) lectin binding for many lectins compared with control and antibiotic groups. This suggests that the intestinal microbiota plays an important role in the expression of sugar moieties in the intestine. Lectins LCA, Phaseolus vulgaris Leucoagglutinin, and Maackia amurensis lectin II showed significant differences (P < 0.05) in lectin bindings between control and antibiotic-fed piglets. This indicates that chlortetracycline as a growth promotant induces biologically relevant changes in the lectin binding profile of the ileum. These findings will help in further understanding the role of the gut microbiota and the mechanisms of action of antibiotics as growth promotants in pigs.     

Weaning — A challenge to gut physiologists

The aim of this paper is to review the most relevant findings obtained over the last four years on the physiology, microbiology and immunology of the gastrointestinal tract of pigs as influenced by weaning and nutrition in the post-weaning period through the action of feed components or alternative substances to in-feed antibiotics. In recent years, some light has been shed on the physiology of the stomach, including motility, gastric emptying and acid secretion. This organ is important in the control of pathogen entry into the intestines. Recent studies on basic intestinal physiology around weaning have been scarce. Most investigations have been devoted to nutritional approaches on the effects of diet components (e.g. protein, fibre, etc.) and alternative substances (e.g. organic acids, zinc, prebiotics, probiotics, other substances of animal or plant origins) on pig performance and various aspects of gastrointestinal tract physiology, microbiology and immunology. Among these, beneficial effects of some organic acids have been confirmed. Additional data with zinc sources include possible mechanisms of protection. Overall it appears that manipulating carbohydrate (prebiotic) composition of the weaning diet may be the most promising way to improve gut health in weaned piglets. In that respect, consistent results have been obtained with lactose supplementation, and interactions with other feed constituents have been studied. Significant positive results have also been produced with probiotics (bacteria, yeasts) fed to the piglets or to the sows. The major parts of the responses appear to be mediated through changes in gastrointestinal microbiology, including enhanced numbers of favourable bacteria (lactobacilli, bifidobacteria) and/or decreased numbers of potentially pathogenic bacteria (Escherichia coli, Clostridia, etc.) together with more favourable profiles of fermentation products along the intestines. In contrast, measurable effects of these dietary factors on intestinal physiology and mucosal immunology have been limited or difficult to interpret in many cases. Finally, investigations have been conducted with varying diet composition (other than carbohydrates: protein source or level, amino acids, etc) or supplementing with different substances of animal or plant origin. However, positive effects on the gut have often been more variable and sometimes inconsistent.     

Herbal plants and their derivatives as growth and health promoters in animal nutrition

The purpose of this review is to summarize the effectiveness, modes of action and commercial application of herbal plants and their derivatives as growth promoters for animal. Feed supplements are a group of feed ingredients that can cause a desired animal response in a non-nutrient role such as pH shift, growth, or metabolic modifier (Hutjens, 1991). Common feed additives used in animal diets include immunostimulators, antimicrobials, antioxidants, pH control agents and enzymes. Herbal plants, are a new class of growth promoters and in recent years this feed additives have gained extensive attention in the feed industry. They are a wide variety of herbs, spices, and products derived thereof, and are mainly essential oils. Although numerous reports have demonstrated antioxidative and antimicrobial and immune stimulation efficacy in vitro, respective experimental in vivo evidence is still quite limited. A limited number of experimental comparisons of herbal plants feed additives with antibiotics or organic acid have suggested similar effects on the animal gut microflora. Gut microflora has significant effects on host nutrition, health, and growth performance by interacting with nutrient utilization and the development of gut system of the host. In addition, some phytogenic compounds seem to promote intestinal mucus production. However, the future of using herbs in animal feeding will in great measure depend on the knowledge of chemical structure, their value and characteristics of practical herbs or their extract physiological needs and well-being of animal, and, above all on consumer’s preferences and expectations.     

饲用益生菌对动物肠道免疫调节的作用机理

益生菌即一类以活菌为主的新型饲料添加剂,其活菌能在动物肠道内定植,维护肠道菌群平衡,并刺激肠黏膜免疫系统,引起体液免疫和细胞免疫应答,从而增强机体抗病力.本文对益生菌的免疫刺激及其作用机理进行综述.     

Antibodies: Alternatives to Antibiotics in Improving Growth and Feed Efficiency

The consolidation of poultry since the 1950s largely depended upon two primary management tools: vaccination and antibiotics. These two tools allowed for the prevention of both bacterial and viral infections that could greatly impact poultry raised in large numbers. Antibiotics were also found to improve poultry growth and feed efficiency over 10% when fed below therapeutic levels. Hence, by the late 1950s, the use of antibiotics for improving growth and feed efficiency in consolidated poultry flocks was commonplace. Early in the discovery of antibiotics, the development of resistance was always a concern, particularly in humans’ consuming animal products that were fed antibiotics. While science never conclusively supported this concern, advocate groups persuaded users of poultry products to avoid foods derived from animals fed antibiotics. Scientists studied the theories supporting the mechanism(s) by which antibiotics improve growth. Products to improve animal performance in the absence of antibiotics have included: enzymes, competitive microbial species, precolonization of the gastrointestinal tract with favorable microbial species, and dietary additives that inhibit microbial attachment to the intestinal mucosa. A recent addition to dietary substances that improve growth and feed efficiency in poultry and other species are egg antibodies that specifically target processes involved in the immune regulation of growth. Antibodies to neuropeptides and the rate-limiting enzyme, phospholipase A₂, in eicosanoid synthesis are presented, along with the hypothesized mechanism of action. Evidence suggested that egg antibodies offer a new strategy in improving the efficiency of animal performance.     

Triennial Growth Symposium: a review of science leading to host-targeted antibody strategies for preventing growth depression due to microbial colonization

In this review, the science used to develop host-targeted therapies for improving animal growth and feed efficiency is presented. In contrast to targeting the microbiota of the host, endogenous host proteins are targeted to regulate an overactive inflammatory response in the host. Activation of the immune/inflammatory systems of an animal is costly in terms of growth and feed efficiency. For example, reduced rates of BW gain and poorer feed efficiency in vaccinated animals compared with nonvaccinated animals have been well documented. Also, the growth rate and feed efficiency of animals colonized by microorganisms is only 80 to 90% of their germ-free counterparts. Further evidence of a cost associated with immune activation is that strategies that enhance the immune capability of an animal can reduce animal growth and feed efficiency. Research now indicates that the growth-promoting effects of antibiotics are indirect, and more likely the result of reduced immune activation due to decreased microbial exposure. Studies of mechanisms by which immune/inflammatory activation reduces animal growth and feed efficiency have shown that cytokines of the acute inflammatory response (i.e., IL-1 and tumor necrosis factor α) are key triggers for host muscle wasting. Cytokine-induced muscle wasting is linked to PG signaling pathways, and it has been proposed that regulation of the PG signaling pathways provide host targets for preventing an overreactive or unwarranted inflammatory event. Intestinal secretory phospholipase A(2) (sPLA(2)) has been found to be a useful and accessible (i.e., found in the intestinal lumen) host target for the regulation of an overreactive inflammatory response to conventional environments. This review presents the science and strategy for the regulation of intestinal sPLA(2) using orally administered egg yolk antibody against the enzyme. Clinically healthy animals fed egg antibodies to sPLA(2) had improved growth and feed efficiency. Literature presented indicates that use of host-targeted strategies for regulating the overexpression of inflammatory processes in an animal may provide new mechanisms to improve animal growth and feed efficiency.