Abstract: 'Gut health' is a term currently gaining much more attentions in veterinary literature especially in poultry. It covers multiple positive aspects of the gastrointestinal (GI) tract, such as the effective digestion by absorption of food, absence of GI illness, normal and stable intestinal microbiota, effective immune status and a state of well-being. Any disturbance or imbalance in above said aspects may influence the gut health. Thus it is necessary to maintain the balance of all possible associated factors related to gut health. Although till date this is being achieved in poultry farming by Antibiotic Growth Promoters (AGPs). However, the growing concern over the transmission and the proliferation of resistant bacteria in human via the food chain has led to a ban of Antibiotic Growth Promoters (AGP) in livestock feed within the European Union since, 2006. As a result, new commercial additives derived from nature have been examined as part of alternative feed strategies for the future. Such products have several advantages over commonly used commercial antibiotics since they are residue free and recognized as safe items in the food industry. Certain natural alternatives recognized by scientific community as Natural Growth Promoters (NGPs) to preserve and maintain the balance of gut microbiota in poultry are summarized in present communication. The article is also enriched with possible mechanisms of action of NGPs with relevant examples by citing research results obtained by various authors in past and current years.
INTRODUCTION
The term ‘gut health’ is currently gaining much more attentions in veterinary literature especially in poultry and has been applied to coordinate the working efficiency of gut (Cummings et al., 2004; Laudadio et al., 2012). Although, the term is restricted to gastro-intestinal (GI) tract only and does not involve other organs (Bischoff, 2011). The gut is the primary site for multitude of processes such as, digestion, fermentation, nutrient absorption, nutrient metabolism, intestinal integrity, immune recognition, immune regulation and development of immune tolerance (Sommer and Backhed, 2013). Gut is mainly composed of physical, chemical, immunological and microbiological components and acts as a selective barrier between the tissues of the bird and its luminal environment (Yegani and Korver, 2008). The gut is the most extensive exposed surface and is constantly exposed to wide variety of potentially beneficial non-infectious as well as harmful infectious agents (Lievin-Le Moal and Servin, 2006). It has been reported that exposure of gut to such harmful infectious agents or pathogens cause an imbalance, which can lead to severe productivity loss, sudden dietary changes, intestinal disease (worm infestation, coccidiosis) and immune suppression (McDevitt et al., 2006). It is now well established that development of antibiotic resistance result from the use of Antibiotic Growth Promoters (AGPs) in animal feed, may be compromised the efficacy of similar antibiotics in therapy for human diseases. Hence, the European Union (EU) introduced a ban on AGPs in 2006, which is now followed in most of the other nations. Before the ban, gut of poultry was highly dependent on Antibiotic Growth Promoters (AGPs) to control intestinal pathogens (Wallace et al., 2010). In view of rising concerns on the extensive loss in poultry due to GI complaints and implementation of strict laws to use of harmful synthetic drug or antibiotics, creates demand of an alternative disease control resources to enhance gut health and to reduce the use of AGPs (Mirzaei-Aghsaghali, 2012). Interest and some useful research on various Natural Growth Promoters (NGPs) such as phytobiotics (essential oils, powders, extracts and phytochemicals), probiotics, prebiotics, synbiotics, organic acid, clay minerals, egg yolk antibodies, exogenous enzymes, recombinant enzymes, nucleotides, polyunsaturated fatty acids and miscellaneous compounds has increased the impetus for revisiting to look for new, useful additives that can enhance gut health and productivity of birds. Utilization of such Natural Growth Promoters (NGPs), as an alternative to AGPs are summarised and explored in the present work by reviewing all possible updated literature till date.
NGPs in poultry gut health: Many alternative substances obtained from nature and belonging to the groups of prebiotics, probiotics, organic acids, enzymes, silicates, herbs and spices etc., have been vigorously tested and evaluated for their potential to replace AGPs in poultry diets (Panda et al., 2006; Khan et al., 2012a, b). Such, alternative substances were referred as Natural Growth Promoters (NGPs). There are a number of such investigated NGPs that are mainly utilised for providing beneficial role for improving health of poultry against various infectious diseases rather than regular nutrition. The involvement of these NGPs in improving of intestinal morphology and nutrient absorption may also encourage the scientists to include these compounds in the diet to improve gut health, promote the growth and overall performance of birds.
Characteristics of ideal NGPs for gut health: Ideally, the NGPs alternatives to AGP should have the same beneficial actions as AGP. Some of key features identified from the most well-known hypothesized mechanism of AGPs to be fulfilled by proposed NGPs (Huyghebaert et al., 2011) that favours performance of gut are: (1) Antimicrobial action, (2) Reduces the incidence and severity of subclinical infections, (3) Reduces the microbial use of nutrients, (3) Improve absorption of nutrients, (4) Reduces the amount of growth-depressing metabolites, (5) Control microbiota shifts, (6) Inhibit the production and excretion of cytokines by immune cells (macrophages) and (7) Shifting the microbiota composition towards one that is less capable of evoking an inflammatory response (Humphrey and Klasing, 2003). Based on the suggested mechanism of action of none of the non-antibiotic NGPs is likely to compensate the loss of gut health. So, it must be emphasised that some strategies will only help to compensate partially by NGPs and will work through indirect mechanisms.
NGPs and their mode of action
Phytobiotics or botanical supplements: Many plants have been reported to possess beneficial multifunctional properties and have been used as feed additives for farm animals in ancient cultures for the same length of time as for human (Huyghebaert et al., 2011). There are many categories of plants products on the basis of physical characters and appearance viz., essential oil, crude or processed plant parts, processed extracts, mixtures of powders or extracts and phytochemicals used for the prevention and treatment of various diseases in farm animals (Sethiya et al., 2013; Dhama et al., 2015). Botanical or herbal extracts, flavours and essential oils (EO) are now fall within the scope of European Commission Regulation 1831/2003. However, unprocessed herbs are still regarded as feed materials and do not need any authorisation (Huyghebaert et al., 2011).
Essential oils: Essential oils are also known as volatile or ethereal oil, obtained from medicinal and aromatic plant materials, which have the characteristic odor or flavor of source plant and are mainly associated for essences and fragrances of plants (Stein and Kil, 2006; Tomer et al., 2010). The major actions exhibited by essential oils are: to increase the release of digestive enzymes and reduce the amount of nutrients available for the growth of bacteria in the lumen of gut (Pasteiner, 2006). The antimicrobial properties of EO have not been fully established but the majority of them shown their effect by changing in lipid solubility at the surface by hydrophobic constituents, which may rupture or disintegrate the outer membrane of bacteria (Dorman and Deans, 2000). A summary of promising EO proven to as a possible sources of NGPs have been shown in Table 1.
Botanicals powder and extracts: Plant-derived products are natural, less toxic, residue free and have been scientifically proven as ideal feed additives in food animal production due to presence of varying degree of growth promoting nutraceuticals components (Wang et al., 1998). The various research conducted to understand the proposed mechanisms by which the botanicals powder and extract mainly exert their beneficial effects are as follows: (1) Disrupt cell membrane of microbes, (2) Interfere with virulence properties of the microbes by increasing the hydrophobicity, which may influence the surface characteristics of microbial cells, (3) Stimulates and proliferate the growth of beneficial bacteria (e.g., lactobacilli and bifidobacteria) in the gut, (4) Act as an immunostimulants, (5) Protects intestine from microbial attack, (6) Stimulate the proliferation and growth of absorptive cells (villus and crypt) in the gastrointestinal tract and (7) Enhances the production and/or activity of the digestive enzymes (Jamroz et al., 2003; Vidanarachchi et al., 2006). Table 2 shows some examples of botanicals powder and extracts with their growth promoting effects on the gut.
Phytochemicals: Phytochemicals are purified single chemical compounds (primary and secondary metabolites) present in cell sap of the naturally occurring plants and may possess some biological significance (Sethiya et al., 2009). The primary mode of action of phytochemicals is to have a significant action on growth inhibition of harmful intestinal microflora in the GI tract. They likely to promote growth by stimulating function of digestive enzymes and organ, e.g., pancreas and small intestine. Changing permeability for cations such as H+ and K+ ions of microbial cell membranes of microorganisms, exhibit growth promotion by oxidation-resistant activity and improvement of the immune system are major proposed mechanisms reported by various researchers by which the phytochemicals exert their antimicrobial activity. A summary of recent update on the effect of some examples of phytochemicals on gut health, in chickens was shown in Table 3.
| Table 1: | Essential oils and their role on poultry gut health |
| Table 2: | Medicinal plants powders/ extract/combinations and their role on poultry gut health |
| Table 3: | Phytochemicals and their role on poultry gut health |
Probiotics: Probiotics are strains of various microbial species, currently has been gained attention as a substitute of antibiotics for poultry production as growth promoters with feed additives (Ahmad, 2006). The various proposed mechanisms by which probiotics act to maintain a beneficial microbial population are: (1) Promote balance of bacteria in the gut by competitive exclusion and antagonism, (2) Involved in gut maturation and integrity, (3) Immune enhancement and preventing inflammation use (4) Improves digestive enzyme activity, (5) Improves feed intake and digestion, (6) Neutralise enterotoxins, (7) Stimulates immune response and (8) Act as growth stimulator (Jin et al., 1997; Simon et al., 2001). Table 4 summarize some examples of probiotic strains and their effects on the gut microbial population of the chicken.
Prebiotics: Prebiotic has been defined as "a non-digestible dietary supplement or feed ingredient that beneficially affects the host by selectively stimulating the growth by altering the composition and metabolism of the gut microbiota" (Gibson and Roberfroid, 1995).
| Table 4: | Probiotics and their role on poultry gut health |
The proposed mechanism by which prebiotics exert their effects are: (1) Growth inhibition of harmful intestinal microbes (through competition for substrates and mucosal attachment sites), (2) Increased intestinal acidity (through production of short-chain fatty acids), (3) Growth stimulation of intestinal absorptive cells and (4) Stimulation of the enteric immune system, thus facilitating better performance and health status of the birds (Gibson and Roberfroid, 1995; Collins and Gibson, 1999; Huyghebaert et al., 2011; Chen et al., 2014). Table 5 summarize some examples of prebiotic and their effects on the gut microbial population of the chicken.
Synbiotics: Synbiotic has been defined as "any combination, which is formed by adding both probiotics and prebiotics to provide the beneficial effects on the gut of birds" (Huyghebaert et al., 2011). This combination could improve the survival and persistence of the health-promoting organism in the gut of birds and can be utilised as alternative to AGP due to its availability as a specific substrate for fermentation and having synergistic action of both probiotics and prebiotics (Yang et al., 2009; Adil and Magray, 2012; Aziz Mousavi et al., 2015). Table 6 summarize some examples of synbiotics with their potential benefits on the intestinal microbial ecosystem of chicken.
Organic acids: Organic acids are group of organic chemicals, composed of carboxylic acid, including fatty acids and amino acids, of the general structure R-COOH (Dibner and Buttin, 2002). In recent years, the use of organic acid has been increased many fold due to its potential to reduce many pathogenic and spoilage organisms by lowering the gut pH (Huyghebaert et al., 2011).
| Table 5: | Prebiotics and their role on poultry gut health |
| Table 6: | Synbiotics and their role on poultry gut health |
| Table 7: | Organic acids and their role on poultry gut health |
They lower the pH, at which the activity of proteases and beneficial bacteria is optimized and proliferation of pathogenic bacteria is minimised by a direct antibacterial effects destroying their cell membranes (Partanen and Mroz, 1999; Chowdhury et al., 2009). Table 7 summarize some examples of organic acids and their effects on the gut microbial population of the birds.
Clay minerals: Clay minerals are natural clay formed by a net of stratified tetrahedral or octahedral layers and mainly composed by molecules of silicon, aluminum and oxygen (Vondruskova et al., 2010). Clays added to the diet can bind and immobilize toxic materials such as aflatoxins and heavy metals etc., may present in the gastrointestinal tract of chicken and thus, reduce toxicity (Owen et al., 2012). As a result of their binding properties, clay minerals have been widely used in poultry diets to improve chicken performance when diets are supposed to contain mycotoxins (Zhou et al., 2014). Some of the molecules of clay minerals such as, bentonites, zeolite, kaolin, montmorillonite, smectite, illite, kaolinite, biotic and clinoptilolite, etc., have been reported to exhibit beneficial effects on the intestinal health of chicken due to additional toxin binding action (Thacker, 2013).
Egg yolk antibodies: Egg yolks antibodies (IgY) are find its application as a potential alternative to antibiotics for growth promotion and have ability to neutralise specific pathogens of gut (Thacker, 2013). In order to produce these antibodies, hens are exposed (usually injected) to antigens of choice to induce desirable immune responses. Normally, these antibodies are then transferred to the egg yolk. Booster dose of immunisation (second exposure) is usually given at a later time to ensure the continued transfer of antibodies from hen to the egg yolk. These antibodies are then extracted from the egg yolk and further processed to be administered directly to the animal or included in the feed (Schade et al., 2005).
Exogenous enzymes: Exogenous enzymes including â-glucanase, xylanase, amylase, ⟨-galactosidase, protease, lipase, phytase, etc., have been supplemented in poultry diets and reported to modulate the gut microbiota of birds (Adeola and Cowieson, 2011). The effects of enzymes on gut microflora were classified into two phases: an ileal phase and a caecal phase. In the ileum, enzymes simply reduce the number of bacteria by increasing the rate of digestion and limiting the amounts of substrates available to the microflora. While, in the caecal phase enzymes produce soluble, poorly absorbed sugars which feed beneficial bacteria. However, the effects of enzymes on the gut microflora may be far more than those two phases (Bedford and Cowieson, 2011).
Recombinant enzymes: The application of genetic engineering allows us to develop targeted enzymes at molecular level for specific purposes. Recently, several enzymes have been developed, which have considerable potential for animal feed application (He et al., 2010). These enzymes have special properties such as, active over a broad pH range, exhibit thermostability, resistant to pepsin and trypsin and viable under simulated gastric conditions. Some typical example includes inclusion of a recombinant carbohydrases and â-mannanase in corn soybean meal diets cause magnitude of the improvement (Pettey et al., 2002).
Nucleotides: Nucleotides are essential components of body involves in cellular metabolism and all intracellular biochemical processes such as, biosynthetic pathways, energy transfer system, as co-enzyme components and as well as biological regulators. Nucleotides alter the cellular lipid metabolism, particularly of long-chain polysaturated fatty acids and the lipoprotein synthesis. Nucleotides changes the composition of intestinal microflora that affect long-chain polyunsaturated fatty acids levels, as some bacteria’s possess necessary enzymes for fatty acid elongation and denaturation and also promote intestinal absorption of iron by conversion of purine nucleotides (AMP, GMP) to inosine, hypoxanthine and uric acid which increase the absorption of iron (Cosgrove, 1998).
Polyunsaturated fatty acids: Polyunsaturated fatty acids (PUFAs) are lipids in which the constituent hydrocarbon chain possesses two or more carbon-carbon double bonds, such as en-3 and n-6 fatty acids which were found to be essential components for the immune function of body’s. Fish oil and corn oil are the main source of feed additive in poultry, contain n-3 and n-6 type polysaturated fatty acids. There are various reports which reflect the utility of these oil for improving gut and overall immunity of the poultry. In another study combination of tuna oil, sunflower oil and palm oil (contain n-3 PUFAs) improves immune responses of birds, as evidenced by the increase in spleen weight, Infectious Bronchitis Disease (IBD), Newcastle Disease (ND), antibody titres, IL-2 and IFN-concentrations (Maroufyan et al., 2012). Conjugated linoleic acid (CLA) is another type of PUFA that has been used as feed supplement to poultry diets and reported for enhancing the immune response, growth of immune tissue, stimulated T-lymphocyte proliferation, elevate, antibody production and maintain the number of LAB in the gut of chicken (He et al., 2007).
Miscellaneous compounds: Many additional compounds have been tested and reported in animals such as spray-dried porcine plasma, yeast culture, bacteriophages, lysozyme, bovine colostrum, lactoferrin and seaweed extract etc. for their potential to replace AGP (Thacker, 2013).
Marketed product survey: Table 8 reported various marketed product thoroughly sold globally as replacement of AGP. Many products from extensive survey were found to full fill the need of AGP in some extent.
| Table 8: | Market product as a source of NGP and their role on poultry gut health |
However, there is still need to set some standards for the replacement of antibiotic compounds in poultry, in terms of product type, identification of suppliers, poultry response criteria, regulatory status and veterinary definition.
CONCLUSION
The potentials of NGPs to AGPs are only of practical significance when they improve animal performance by maintaining gut health and immune functions in given time slot levels. Such thoroughly tested microbiota modulating and immunomodulatory compounds have potential to be used as feed stuff of feed additives for poultry productions. Although market is flooded with numerous products, some of them shown their potential, but at the same time there are many more objectionable products, where efficacy is still questionable. Therefore, there is an urgent need of further studies to develop larger datasets for product based mechanisms of action of each compound in a scientific way. The paper presented list of various NGPs are by no means of exhaustive and there are also many other products design and screened using these requirements day to day claiming to be of value added NGPs in gut health.