Probiotic Modes of Action and Its Effect on Biochemical Parameters and Growth Performance in Poultry

Document Type: Review Articles


Department of Biochemistry, Veterinary Directorate, Kafr Elshiekh, Egypt


Provide a healthy diet is one of the major health challenges in the world to maintain health and nutritional status of populations. In this reason, new control strategies such as probiotics have been applied as prophylactic and therapeutic instead of antibiotics. In the same line, probiotics have antagonistic effects to various microorganisms proposed in several mechanisms including improvement of gut epithelial barrier function, competition on adhesive receptors, competition on available nutrients, antibacterial effects, degradation and neutralization of toxins and immunomodulatory effect. Furthermore, probiotics have significant impacts on biochemical parameters and could be used as substitutional supplements do health benefits including hypocholesterolemia and reduction of blood glucose. Probiotics have been explained to hypocholesterolemia and hypoglycemia through several mechanisms. Moreover, the use of probiotics in feeds enhances the protein utility in feedstuff. Thus, this review was attempted to spot generally insight on the modes of action of probiotics and its importance biochemically.



From many decades, antibiotics have been used in poultry feeds but now prohibited in many countries. The enteric pathogens are most common and associated diseases in poultry industry due to lack of knowledge about application of biosecurity measures that result to spread of infection. Antibiotics have been used for controlling the infection and as growth promoters. Due to several negative effects for antibiotics such as increasing the antibiotic resistances to pathogenic microorganisms and presence of their residues in poultry products that pose the health hazard to consumer therefore, it has brought a call for worldwide antibiotic prohibit. Concerning with food safety has given rise to challenge for productive efficiency. The poultry industry represents among the highest sources of protein production as well as increasing in the size of poultry industry is faster than other food producing animal industries (Lyayi, 2008; Ohimain and Ofongo, 2012). Unfortunately, overuse of antibiotics for veterinary purposes led to presence of resistant bacteria. Therefore, the issue of controlling pathogenic bacteria without antibiotics became the great challenge (Ohimain and Ofongo, 2012; Wallace et al. 2010). Such infections are responsible for loss productivity and increase of mortality in poultry industry (Patterson and Burkholder, 2003). In the light of growing concerns over excessive mortality rate because of gastrointestinal problems and restrictions in usage of antibiotics thus, it is a very necessary to find alternative method to improve gut health and reduce the productivity losses. Probiotics are used as prospective substitute for antibiotic in poultry because of its side effects on consumers and manufactures. Probiotics are defined as a group of beneficial live microorganisms to host by reducing the gut pathogens. This improves the health status, production performances and feed conversion rate as well as immune response of poultry and farm animals (Getachew, 2016; Sethiya, 2016; Smith, 2014). The lactic acid bacteria of genus Lactobacillus and Bifidobacterium are the main bacteria reported in probiotics. Besides, different bacteria species and yeast have been used in probiotics as Bacillus, Lactococcus, Streptococcus, Enterococcus, Pediococcus, Saccharomyces cerevisiae and Toulopsis sphaerica (Jadhav et al. 2015; Jeong and Kim, 2014; Lee et al. 2010a). Furthermore, killed bacteria cultures, bacterial metabolites and fungi such as mushroom have been also included (Jadhav et al. 2015; Mahfuz et al. 2017; Willis et al. 2011). Bacillus subtilis spores one of bacterial species used as probiotics that has several advantages in poultry industry like heat resistance during feed manufacture, bearing gastric acidicity, storage for long period at room temperature and have immune stimulant and antimicrobial activities (Cutting, 2011; Lee et al. 2010b; Lee et al. 2010c). This review is aimed to explain mechanism of probiotics action and investigate its effect on biochemical parameters and immune response in poultry.


Mechanisms of probiotics action

Under normal circumstances, the sources of microbial are either autochthonous bacterial colonies by environmental exposure and normal feeding activities or allochthonous by introducing them as dietary supplementation through feeding or drinking water as probiotics (Chichlowski et al. 2007a; Chichlowski et al. 2007b; Patterson and Burkholder, 2003). Several studies have reported that commensal bacteria improve the gut health and inhibit pathogens but sometimes suffering from disturbances result in sensitivity to infection (reviewed byDhama et al. 2011). Besides, the size and complexity of microbial population are important factors in controlling pathogens (Mead, 2005). The probiotic may contain one or a cocktail of variant bacterial species/ strains and the mode of action of each one may differ. So, there are possibilities for probiotics action include competition between native organisms and pathogens for adhesive receptors in intestinal epithelium, competition for available nutrients, establishment environmental condition by decrease pH, direct antimicrobial effect by releasing antibacterial substances and neutralization of toxins, aggregation with pathogenic bacteria and stimulation of immune system (Dhama and Singh, 2010; Ng et al. 2009; Otutumi et al. 2012). It is necessary for maintenance the healthy gut microflora to improve the microbial environment by replacing the pathogenic bacteria. Since the pathogenic bacteria multiply faster than the native bacteria occurrence the infection. The equilibrium between favorable and unfavorable is a crucial. This equilibrium may affect by environmental factors or internal factors like stress. Probiotics are capable of adherence and colonize to the epithelial surface of gut and competing with pathogen to adhesion site forming the enterocytes complexity and facilitate the interaction amongst cell types, thus raise the amplitude of phagocytosis (Bene et al. 2017; Trejo et al. 2006). For instance, Lactobacillus plantarum compete with E. coli for adhesion site by induction MUC3 mucins (Mack et al. 1999). Probiotics help in utilization of nutrients such as digestible protein, vitamins, minerals and enzymes. In addition, they help in vitamin synthesis (Biotin, B1, B2, B12 and K) and mineral metabolism that are important for proper growth and metabolism (Dhama and Singh, 2010). Furthermore, probiotics compete with pathogens for available nutrients preventing them from growth and multiplication in intestine (Bajaj et al. 2015). For instance, Bifidobacterium adolescentis S2-1 competes with Porphyromonas gingivalis on vitamin K (Hojo et al. 2007).  A variety of primary and secondary metabolites such as volatile fatty acids, oraganic acids and lactic acid lowering the intestinal pH to inhibit the pathogens growth such as Salmonella and E. coli (Marteau et al. 2004). For example, Lactobacilli produce lactic acid and indirectly increase butyric acid concentration in gut that induce the growth and proliferation of butyric acid producing bacteria through cross-feeding phenomena (Van Immerseel et al. 2009). However, it inhibits the pathogens and enhances decomposing of organic matter such as cellulose and lignin without occurring any harmful effects arising from its fermentation (Higa and Parr, 1994). Probiotics produce the antibacterial substances to kill / inhibit the pathogenic microorganisms including bacteriocins, organic acids such as acetate and lactate, lysosomes, lactoferrin, lactoperoxidase and hydrogen peroxide (Jin et al. 1997). For example, Lactobacillus crispatus F117 produce the highest level of hydrogen peroxide inhibiting Staphylococcus aureus growth (Ocana et al. 1999). In addition, they release anti-enterotoxin substances including acidophilin, acidolin and lactin like Lactobacillus bulgaricus capable of neutralizing and / or absorption of enterotoxins produced by pathogens. Furthermore, they produce useful substances such as enzymes, hormones and vitamins that vital for favorable microorganisms' multiplication. They decrease urease activity in gut subsequently, reducing the concentration of non protein nitrogen, uric acid, ammonia and urea that result in lowering the ammonia formation in litter. Excess of ammonia concentration in litter causes kerato-conjunctivitis and associated problems in poultry farms. Therefore, it was reported that Bacillus subtilis and Streptococcus faecium have ability to reduce ammonia concentration in excreta (Fuller, 2001; Hajati and Rezaei, 2010; Vegad, 2004). Probiotics have a significant impact on the immunity system of poultry against invading pathogens. Probiotics induce both innate immunity and adaptive immunity via regulation of Toll-like receptors expression, activation both dendritic cells and natural killer cells, in addition increasing the responses of T-helper cells, induction cytokines production and immunoglobines secretion like IgM, IgG and IgA (Alkhalf et al. 2010; Janardhana et al. 2009; Tsai et al. 2012). Probiotics increase the number of lymphocytes in gut associated lymphoid tissues like payer's patches and intestinal mucosal cells thereby providing the local immunity by IgA secretion producing plasma cells (Haghighi et al. 2006). The intestinal plasma cells participated in production of T-cells independent antibodies against pathogens as an evasive mechanism (Jiang et al. 2004). In addition, the intestinal enterocytes acts as a barrier to loss of nutrients to pathogens thereby help the immune system to recognize the pathogens.


Effect of probiotics on enteric pathogens

The idea of competitive exclusion of pathogenic microorganisms by beneficial one such as Lactobacilli, prevent the pathogens from adherence to gut surface and removed from intestine via ingest. It was one of the spreading keys of probiotics in poultry and livestock production systems which inhibit the harmful effect of pathogens such as E. coli, Salmonella, Clostridia, Campylobacter (Jin et al. 1997). Mulder (1991) illustrated that administration of probiotics orally reduces occurrence of Salmonella infection in chicks. A mixture of three different probiotics has a therapeutic effect on post infectious irritable bowel syndrome caused by Trichinella spiralis (Wang et al. 2014). Lactobacilli and Bifidobacteria have been exhibited a strong killing activity against a wide range of pathogenic microorganisms like E. coli, Salmonella, Listeria monocytogenes, Campylobacter pylori and Rotavirus (Bermudez-Brito et al. 2012; Bujalance et al. 2014). Probiotics degrade toxin receptors on intestinal mucosa via enzymatic mechanismsuch as Saccharomyces boulardii protect the host against Clostridium difficile infection through suppression toxin production in ileum of rabbits and also can produce polyamines that inhibit secreted toxins of cholera infection in jejunum of rats (Bermudez-Brito et al. 2012; Valdes-Varela et al. 2018). Moreover, probiotics have a significant role in development of immune response against Newcastle disease, tetanus toxoid and Clostridium perfringens alpha-toxin (Anjum, 1998; Haghighi et al. 2006). Probiotics can enhance stimulation of nonspecific immunity like induction phagocytic activity of macrophages, promote the immunoglobulins secretion and immune cells proliferation (Kaur et al. 2009). Previous study was observed level of serum antibodies production usually IgG, IgM and interferon γ increased after addition of probiotic to diet (Ahmed, 2006).


Effect of probiotics on biochemical parameters

Many previous literatures reported impact of probiotics on biochemical parameters in poultry. Probiotics have a significant improvement levels of total unsaturated fatty acids, omega 6 and essential poly unsaturated fatty acids like linoleic acid and linolenic acid in egg yolk (Tang et al. 2016; Yi et al. 2014). Pervious study demonstrated that probiotics reduced total cholesterol and triglyceride in blood (Taranto et al. 2000). However, other studies reported that probiotics hadn’t a significant difference on levels of total cholesterol (Greany et al. 2004; Pelicano et al. 2004). Previous studies have been demonstrated cholesterol lowering effect of probiotics through several mechanisms. It has been hypothesized that enzymatic deconjugation of bile acid by hydrolase enzyme. Cholesterol is the end product of bile which is stored and concentrated in gallbladder then released on ingested food in duodenum. Once deconjugation, part of bile salt reabsorption by enterohepatic circulation into liver. Cholesterol reused in new bile acid synthesis leading to lowering serum cholesterol. Probiotics can uptake cholesterol and exploit it in cell walls (Begley et al. 2006; Jones et al. 2004; Lye et al. 2009) and cellular membrane synthesis during growth in small intestine lead to increase the cell membrane strength thereby preserve the cellular resistance from fragmentation (Lye et al. 2010a). Another mechanism occurs by cholesterol conversion into copresterol then directly excreted in feces. Sterolibacterium denitrificans secrete cholesterol dehydrogenase that catalyze transformation of cholesterol into copresterol via intermediate factor (Chiang et al. 2008). Furthermore, another study reported that Lactobacillus acidophilus, L. bulgaricus and L. casei ATCC 393 were also shared into conversion of cholesterol into copresterol (Lye et al. 2010b). Probiotics can ferment probiotic in intestine producing short chain fatty acids such as propionate. Propionate acts as an effective inhibitor for fatty acids synthesis and control of cholesterol synthesis in the liver subsequently, it leads to decrease the plasma cholesterol levels (Trautwein et al. 1998). Regarding to effect of probiotics on blood glucose levels, previous study showed increasing of blood glucose level by probiotic supplements in feeding (Das et al. 2005). However, other studies on human observed that Lactobacillus and Bifidobacteria reduce blood glucose level (Asemi et al. 2013; Ejtahed et al. 2012; Eslamparast et al. 2014). For example, some studies investigated a significant improvement in blood glucose level after ingestion of probiotics for 6 weeks (Ejtahed et al. 2012). It has been speculated that probiotics induce glucose absorption through insulinotropic polypeptides and glucagon like peptides production (Al-Salami et al. 2008). This mechanism has been explained that certain probiotics such as Lactobacillus casei, L. plantarum, L. acidophilus, L. delbrueckii subsp. bulgaricus, Bifidobacterium longum, B. breve, B. infantis and Streptococcus salivarius subsp. Thermophilus produce short chain fatty acids that promote the butyrate secretion of glucagon-like peptide-1. Glucagon-like peptide-1 hormone was secreted by L-cells in intestine resulting to stimulate insulin secretion and inhibits glucagon (Belenguer et al. 2006; Yadav et al. 2013). This secretion leads to delay gastric empty and reduce the appetite, food intake and body weight gain (Drucker and Nauck, 2006). Lactic acid bacteria produce lactate and then fermented into acetate and propionate via methylmalonyl-CoA or acrylyl-CoA reductase and then to butyrate via acetyl-CoA (Belenguer et al. 2006; Seeliger et al. 2002). Other mechanisms for probiotics could be correlated with improvement immune system through increased anti-inflammatory cytokine production, decreased intestinal permeability and inhibit oxidative stress (Ma et al. 2004; Paszti-Gere et al. 2012; Yadav et al. 2008). Probiotic additions accompanied with an elevation of glutathione peroxidase, superoxide dismutase activities and total antioxidant status. Under nuclear factor-κB regulation, probiotics can inhibit the inhibitor of NF-κB kinase subunit β breakdown subsequently, prevent NF-κB move into the nucleus and inhibit pro-inflammatory cytokines expression as well as up-regulated nerve growth factor (Lambiase et al. 1997; Ma et al. 2003; Pierucci et al. 2001). Therefore, these findings showed increasing probiotics efficacy to inhibit streptozotocin-induced changes in blood glucose by increasing antioxidants on pancreatic β-cells (Yadav et al. 2008). Several studies drew an attention towards importance of probiotics in improving the feed utilization efficacy. Probiotic supplementation enhanced digestibility, improved animal growth performance and reduced the quantity of feed consumed (Bedford and Schulze, 1998). Addition of probiotics to low protein diets of broiler chickens showed a significant positive effect on body weight gain, and reduced the protein degradation and ammonia formation (Mehr et al. 2007). However, probiotics feeding had no any influence serum protein level (Gohain and Sapcota, 1998). While serum uric acid levels were significantly increased with the increasing of probiotics levels in broiler (Hamid and Qureshi, 2009; Sultan and Abdul- Rahman, 2011). However, there were no any changes in kidneys of mice that treated with probiotics may be as a result to serum uric acid level was at tolerance level (Salahuddin et al. 2013).


Influence of probiotics on growth performance

Several studies have been illustrated that probiotics promote growth performance in the poultry production system compared with non-supplement diets (Kalavathy et al. 2003; Mountzouris et al. 2010; Shim et al. 2010). Midilli and Tuncer (2001) showed significantly improved growth performance in broiler that administered with probiotic orally. Administration of probiotics in diets enhances organic acid production like lactic acid can prevent the gastrointestinal disorders and improve feed efficiency. Therefore, it was observed a significant improve in weight gain between 21day and 42 day in broiler (Jin et al. 1998). However, some studies reported that probiotics had no influence on food consumption, but it improve growth rate and carcass weight of broiler (Djouvinov et al. 2005a; Djouvinov et al. 2005b). From the best of my knowledge there is limited information about the effective doses of probiotics that used in poultry and animal production systems. Meanwhile, the application of probiotics on poultry production differs than animal production because of difference of their life span and physiological status. Furthermore, the impact of probiotics poultry health and their productivity depends on many factors such as the type of probiotic (lactobacilli, bifidobacteria, yeasts, …), the daily dose, the timing and the frequency of daily administration, the method of delivery, the duration of administration, and the viability of the probiotic. It is very important to keep the viability of probiotic from destroying the external factors via microencapsulation.



This article attempted to spot an overview on the modes of action of probiotics and their impacts on biochemical parameters and growth performance. Recently, many research centers focused the importance of probiotics usage as antibiotic substitution. Moreover, probiotics have a significant potential effect for different diseases. Several important mechanisms demonstrate the antagonistic effect of probiotics on pathogens including competition on adhesion receptors, competition for available nutrients and production inhibitory substances, improvement the gut epithelial barrier function, degradation and neutralization of toxins and immune-stimulatory effect. Biochemically, probiotics have beneficial effect in treatment of chloesterolemia and alleviation of blood glucose. It is necessary for enhancement the poultry resistance to bacterial and viral diseases through promoting the immune response to the pathogens. It was recommended that dietary inclusion of probiotics from 21 day to 42 day of age in broiler chicken, while it had a significant effect on growth performance. The efficacy of probiotic depends on the type of bacteria present in probiotic, dose (107-1010 CFU/bird/day) and types of the gastrointestinal microbial population.

Ahmed A. (2006). Effect of probiotics on broilers performance Int. J. Poul. Sci. 5, 593-597.

Alkhalf A., Alhaj M. and Al-Homidan I. (2010). Influence of probiotic supplementation on immune response of broiler chicks. Egyptian Poult. Sci. 30, 271-280.

Al-Salami H., Butt G., Fawcett J.P., Tucker I.G., Golocorbin-Kon S. and Mikov M. (2008). Probiotic treatment reduces blood glucose levels and increases systemic absorption of gliclazide in diabetic rats. European J. Drug Metab. Pharmacokinet. 33, 101-106.

Anjum A. (1998). Layer production with EM-technology. Pp. 28-35 in Proc. 7th Int. Conf. Technol. Effect. Microorgan.,Bali, Indonesia.

Asemi Z., Zare Z., Shakeri H., Sabihi S.S. and Esmaillzadeh A. (2013). Effect of multispecies probiotic supplements on metabolic profiles, hs-CRP, and oxidative stress in patients with type 2 diabetes. Ann. Nutr. Metab. 63, 1-9.

Bajaj B.K., Claes I.J. and Lebeer S. (2015). Functional mechanisms of probiotics. J. Microbiol. Biotechnol. Food Sci. 4, 321-327.

Bedford M.R. and Schulze H. (1998). Exogenous enzymes for pigs and poultry. Nutr. Res. Rev. 11, 91-114.

Begley M., Hill C. and Gahan C.G. (2006). Bile salt hydrolase activity in probiotics. Appl. Environ. Microbiol. 72, 1729-1738.

Belenguer A., Duncan S.H., Calder A.G., Holtrop G., Louis P., Lobley G. and Flint H.J. (2006). Two routes of metabolic cross-feeding between Bifidobacterium adolescentis and butyrate-producing anaerobes from the human gut. Appl. Environ. Microbiol. 72, 3593-3599.

Bene K.P., Kavanaugh D.W., Leclaire C., Gunning A.P., MacKenzie D.A., Wittmann A., Young I.D., Kawasaki N., Rajnavolgyi E. and Juge N. (2017). Lactobacillus reuteri surface mucus adhesins upregulate inflammatory responses through interactions with innate C-type lectin receptors. Front. Microbiol. 8, 321-326.

Bermudez-Brito M., Plaza-Diaz J., Munoz-Quezada S., Gomez-Llorente C. and Gil A. (2012). Probiotic mechanisms of action. Ann. Nutr. Metab. 61, 160-174.

Bujalance C., Jiménez-Valera M., Moreno E., Ruiz-López M. D., Lasserrot A. and Ruiz-Bravo A. (2014). Lack of correlation between in vitro antibiosis and in vivo protection against enteropathogenic bacteria by probiotic lactobacilli. Res. Microbiol. 165, 14-20.

Chiang Y.R., Ismail W., Heintz D., Schaeffer C., Van Dorsselaer A. and Fuchs G. (2008). Study of anoxic and oxic cholesterol metabolism by Sterolibacterium denitrificans. J Bacteriol. 190, 905-914.

Chichlowski M., Croom J., McBride B.W., Daniel L., Davis G. and Koci M.D. (2007a). Direct-fed microbial PrimaLac and salinomycin modulate whole-body and intestinal oxygen consumption and intestinal mucosal cytokine production in the broiler chick. Poult. Sci. 86, 1100-1106.

Chichlowski M., Croom W.J., Edens F.W., McBride B.W., Qiu R., Chiang C.C., Daniel L.R., Havenstein G.B. and Koci M.D. (2007b). Microarchitecture and spatial relationship between bacteria and ileal, cecal, and colonic epithelium in chicks fed a direct-fed microbial, PrimaLac, and salinomycin. Poult. Sci. 86, 1121-1132.

Cutting S.M. (2011). Bacillus probiotics. Food Microbiol. 28, 214-220.

Das H.K., Medhi A.K. and Islam M. (2005). Effect of probiotics on certain blood parameter and carcass characteristics of broiler chicken. Indian J. Poult. Sci. 40, 83-86.

Dhama K. and Singh S.D. (2010). Probiotics improving poultry health and production: An overview. Poult. Punch. 26(3), 41-46.

Dhama K., Verma V., Sawant P.M., Tiwari R., Vaid R.K. and Chauhan R.S. (2011). Applications of probiotics in poultry: Enhancing immunity and beneficial effects on production performances and health: A review. J. Immunol. Immunopathol. 13(1), 1-19.

Djouvinov D., Stefanov M., Boicheva S. and Vlaikova T. (2005a). Effect of diet formulation on basis of digestible amino acids and supplementation of probiotic on performance of broiler chicks. Trakia J. Sci. 3, 61-69.

Djouvinov D., Svetlana B., Tsvetomira S. and Tatiana V. (2005b). Effect of feeding lactina probiotic on performance, some blood parameters and caecal microflora of mule ducklings. Trakia J. Sci. 3, 22-28.

Drucker D.J. and Nauck M.A. (2006). The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 368, 1696-1705.

Ejtahed H.S., Mohtadi-Nia J., Homayouni-Rad A., Niafar M., Asghari-Jafarabadi M. and Mofid V. (2012). Probiotic yogurt improves antioxidant status in type 2 diabetic patients. Nutrition. 28, 539-543.

Eslamparast T., Zamani F., Hekmatdoost A., Sharafkhah M., Eghtesad S., Malekzadeh R. and Poustchi H. (2014). Effects of synbiotic supplementation on insulin resistance in subjects with the metabolic syndrome: a randomised, double-blind, placebo-controlled pilot study. Br. J. Nutr. 112, 438-445.

Fuller R. (2001). The chicken gut micro flora and probiotic supplements. J. Poult. Sci. 38, 189-196.

Getachew T. (2016). A review on effects of probiotic supplementation in poultry performance and cholesterol levels of egg and meat. J. World Poult. Res. 6, 31-36.

Gohain A.K. and Sapcota D. (1998). Effect of probiotics feeding on the performance of broilers. Indian J. Poult. Sci. 33, 101-105.

Greany K.A., Nettleton J.A., Wangen K.E., Thomas W. and Kurzer M.S. (2004). Probiotic consumption does not enhance the cholesterol-lowering effect of soy in postmenopausal women. J. Nutr. 134, 3277-3283.

Haghighi H.R., Gong J., Gyles C.L., Hayes M.A., Zhou H., Sanei B., Chambers J.R. and Sharif S. (2006). Probiotics stimulate production of natural antibodies in chickens. Clin. Vaccine Immunol. 13, 975-980.

Hajati H. and Rezaei M. (2010). The application of probiotics in poultry production. Int. J. Poult. Sci. 9, 298-304.

Hamid M. and Qureshi A. (2009). Trial study on the efficacy of protexin (water-soluble) on the performance of broilers. Pakistan Vet. J. 21, 224-225.

Higa T. and Parr J. (1994). Beneficial and Effective Microorganisms for a Sustainable Agriculture and Environment. InternationalNature FarmingResearch Center,University of Ryukyus Okinawa, Atami, Japan.

Hojo K., Nagaoka S., Murata S., Taketomo N., Ohshima T. and Maeda N. (2007). Reduction of vitamin K concentration by salivary Bifidobacterium strains and their possible nutritional competition with Porphyromonas gingivalis. J. Appl. Microbiol. 103, 1969-1974.

Jadhav K., Sharma K.S., Katoch S., Sharma V.K. and Mane B.G. (2015). Probiotics in broiler poultry feeds: A review. J. Anim. Nutr. Physiol. 1, 4-16.

Janardhana V., Broadway M.M., Bruce M.P., Lowenthal J.W., Geier M.S., Hughes R.J. and Bean A.G. (2009). Prebiotics modulate immune responses in the gut-associated lymphoid tissue of chickens. J. Nutr. 139, 1404-1409.

Jeong J.S. and Kim I.H. (2014). Effect of Bacillus subtilis C-3102 spores as a probiotic feed supplement on growth performance, noxious gas emission, and intestinal microflora in broilers. Poult. Sci. 93, 3097-3103.

Jiang H.Q., Thurnheer M.C., Zuercher A.W., Boiko N.V., Bos, N.A. and Cebra J.J. (2004). Interactions of commensal gut microbes with subsets of B- and T-cells in the murine host. Vaccine. 22, 805-811.

Jin L.Z., Ho Y.W., Abdullah N. and Jalaludin S. (1997). Probiotics in poultry: Modes of action. World’s Poult. Sci. J. 53, 351-368.

Jin L.Z., Ho Y.W., Abdullah N. and Jalaludin S. (1998). Growth performance, intestinal microbial populations, and serum cholesterol of broilers fed diets containing Lactobacillus cultures. Poult. Sci. 77, 1259-1265.

Jones M.L., Chen H., Ouyang W., Metz T. and Prakash S. (2004). Microencapsulated genetically engineered Lactobacillus plantarum 80 (pCBH1) for bile acid deconjugation and its implication in lowering cholesterol. J. Biomed. Biotechnol. 2004, 61-69.

Kalavathy R., Abdullah N., Jalaludin S. and Ho Y.W. (2003). Effects of Lactobacillus cultures on growth performance, abdominal fat deposition, serum lipids and weight of organs of broiler chickens. Br. Poult. Sci. 44, 139-144.

Kaur I.P., Kuhad A., Garg A. and Chopra K. (2009). Probiotics: delineation of prophylactic and therapeutic benefits. J. Med. Food. 12, 219-235.

Lambiase A., Bracci-Laudiero L., Bonini S., Starace G., D'Elios M.M., De Carli M. and Aloe L. (1997). Human CD4+ T-cell clones produce and release nerve growth factor and express high-affinity nerve growth factor receptors. J. Allergy Clin. Immunol. 100, 408-414.

Lee K., Lillehoj H.S. and Siragusa G.R. (2010a). Direct-fed microbials and their impact on the intestinal microflora and immune system of chickens. J. Poult. Sci. 47, 106-114.

Lee K.W., Lee S.H., Lillehoj H.S., Li G.X., Jang S.I., Babu U.S., Park M.S., Kim D.K., Lillehoj E.P., Neumann A.P., Rehberger T.G. and Siragusa G.R. (2010b). Effects of direct-fed microbials on growth performance, gut morphometry, and immune characteristics in broiler chickens. Poult. Sci. 89, 203-216.

Lee K.W., Lillehoj H.S., Jang S.I., Li G., Lee S.H., Lillehoj E.P. and Siragusa G.R. (2010c). Effect of Bacillus-based direct-fed microbials on Eimeria maxima infection in broiler chickens. Comp. Immunol. Microbiol. Infect. Dis. 33, 105-110.

Lyayi E.A. (2008). Prospectsand challenges of unconventional poultry feedstuffs. Nigerian Poult. Sci. J. 5, 186-194.

Lye H.S., Kuan C.Y., Ewe J.A., Fung W.Y. and Liong M.T. (2009). The improvement of hypertension by probiotics: Effects on cholesterol, diabetes, renin, and phytoestrogens. Int. J. Mol. Sci. 10, 3755-3775.

Lye H.S., Rusul G. and Liong M.T. (2010a). Mechanisms of cholesterol removal by Lactoballi Under conditions that mimic the human gastrointestinal tract. Int. Dairy J. 20, 169-175.

Lye H.S., Rusul G. and Liong M.T. (2010b). Removal of cholesterol by Lactobacilli via incorporation of and conversion to coprostanol. J. Dairy Sci. 93, 1383-1392.

Ma D., Forsythe P. and Bienenstock J. (2004). Live Lactobacillus rhamnosus [corrected] is essential for the inhibitory effect on tumor necrosis factor alpha-induced interleukin-8 expression. Infect. Immun. 72, 5308-5314.

Ma D., Wolvers D., Stanisz A.M. and Bienenstock J. (2003). Interleukin-10 and nerve growth factor have reciprocal upregulatory effects on intestinal epithelial cells. Am. J. Physiol. Regul. Integr. Comp. Physiol. 284, 1323-1329.

Mack D.R., Michail S., Wei S., McDougall L. and Hollingsworth M.A. (1999). Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression. Am. J. Physiol. 276, 941-950.

Mahfuz S.U., Hui S. and Zhongjun L. (2017). Improved production performance and health status with winter mushroom stem (Flammulina velutipes) in laying chicken: Review. Int. J. Poult. Sci. 16, 112-117.

Marteau P., Seksik P., Lepage P. and Dore J. (2004). Cellular and physiological effects of probiotics and prebiotics. Mini Rev. Med. Chem. 4, 889-896.

Mead G.C. (2005). Food Safety Control in the Poultry Industry. Woodhead Publishing Limited, Cambridge, United Kingdom.

Mehr M.A., Shargh M.S., Dastar B., Hassani S. and Akbari M. (2007). effect of different levels of protein and protein on broiler performance. Int. J. Poult. Sci. 6(8), 573-577.

Midilli M. and Tuncer S.D. (2001). The effects of enzyme and probiotic supplementation to diets on broiler performance. Turkish J. Vet. Anim. Sci. 12, 895-903.

Mountzouris K.C., Tsitrsikos P., Palamidi I., Arvaniti A., Mohnl M., Schatzmayr G. and Fegeros K. (2010). Effects of probiotic inclusion levels in broiler nutrition on growth performance, nutrient digestibility, plasma immunoglobulins, and cecal microflora composition. Poult. Sci. 89, 58-67.

Mulder R.W.A.W. (1991). Probiotics as a tool against Salmonella contamination. World Poult. Misset. 7, 6-7.

Ng S.C., Hart A.L., Kamm M.A., Stagg A.J. and Knight S.C. (2009). Mechanisms of action of probiotics: Recent advances. Inflamm. Bowel Dis. 15, 300-310.

Ocana V.S., Pesce de Ruiz Holgado A.A. and Nader-Macias M.E. (1999). Selection of vaginal H2O2-generating Lactobacillus species for probiotic use. Curr. Microbiol. 38, 279-284.

Ohimain E.I. and Ofongo R.T.S. (2012). The effect of probiotic and prebiotic feed supplementation on chicken health and gut microflora: A Review. Int. J. Anim. Vet. Adv. 4, 135-143.

Otutumi L., Gois M., de Moraes Garcia E. and Loddi M. (2012). Variations on the efficacy of probiotics in poultry. Pp. ??? in Probiotics in Animals, E. Rigobelo, Ed. IntechOpen, London, United Kingdom.

Paszti-Gere E., Szeker K., Csibrik-Nemeth E., Csizinszky R., Marosi A., Palocz O., Farkas O. and Galfi P. (2012). Metabolites of Lactobacillus plantarum 2142 prevent oxidative stress-induced overexpression of proinflammatory cytokines in IPEC-J2 cell line. Inflammation. 35, 1487-1499.

Patterson J.A. and Burkholder K.M. (2003). Application of prebiotics and probiotics in poultry production. Poult. Sci. 82, 627-631.

Pelicano E., Souza P. and Souza H. (2004). Performance of broilers fed diets containing natural growth promoters. Rev. Bras. Cienc. Avic. 6(4), 231-236.

Pierucci D., Cicconi S., Bonini P., Ferrelli F., Pastore D., Matteucci C., Marselli L., Marchetti P., Ris F., Halban P., Oberholzer J., Federici M., Cozzolino F., Lauro R., Borboni P. and Marlier L.N. (2001). NGF-withdrawal induces apoptosis in pancreatic beta cells in vitro. Diabetologia. 44, 1281-95.

Salahuddin M., Akhter H., Akter S., Miah M. and Ahmad N. (2013). Effects of probiotics on haematology and biochemical parameters in mice. Bangladesh Veterinarian. 30(1), 20-24.

Seeliger S., Janssen P.H. and Schink B. (2002). Energetics and kinetics of lactate fermentation to acetate and propionate via methylmalonyl-CoA or acrylyl-CoA. FEMS Microbiol. Lett. 211, 65-70.

Sethiya N.K. (2016). Review on natural growth promoters available for improving gut health of poultry: An alternative to antibiotic growth promoters. Asian J. Poult. Sci. 10, 1-29.

Shim Y.H., Shinde P.L., Choi J.Y., Kim J.S., Seo D.K., Pak J.I., Chae B.J. and Kwon I.K. (2010). Evaluation of multimicrobial probiotics produced by submerged liquid and solid substrate fermentation methods in broilers. Asian Australasian J. Anim. Sci. 23, 521-529.

Smith J.M. (2014). A review of avian probiotics. J. Avian Med. Surg. 28, 87-94.

Sultan K. and Abdul-Rahman S. (2011). Effect of probiotic on some physiological parameters in broiler breeders. Int. J. Poult. Sci. 10, 626-628.

Tang C., Hoo P.C., Tan L.T., Pusparajah P., Khan T.M., Lee L.H., Goh B.H. and Chan K.G. (2016). Golden needle mushroom: A culinary medicine with evidenced-based biological activities and health promoting properties. Front. Pharmacol. 7, 474-482.

Taranto M.P., Medici M., Perdigon G., Ruiz Holgado A.P. and Valdez G.F. (2000). Effect of Lactobacillus reuteri on the prevention of hypercholesterolemia in mice. J. Dairy Sci. 83, 401-403.

Trautwein E.A., Rieckhoff D. and Erbersdobler H.F. (1998). Dietary inulin lowers plasma cholesterol and triacylglycerol and alters biliary bile acid profile in hamsters. J. Nutr. 128, 1937-1943.

Trejo F.M., Minnaard J., Perez P.F. and De Antoni G.L. (2006). Inhibition of Clostridium difficile growth and adhesion to enterocytes by Bifidobacterium supernatants. Anaerobe. 12, 186-193.

Tsai Y.T., Cheng P.C. and Pan T.M. (2012). The immunomodulatory effects of lactic acid bacteria for improving immune functions and benefits. Appl. Microbiol. Biotechnol. 96, 853-862.

Valdes-Varela L., Gueimonde M. and Ruas-Madiedo P. (2018). Probiotics for prevention and treatment of Clostridium difficile infection. Adv. Exp. Med. Biol. 1050, 161-176.

Van Immerseel F., De Zutter L., Houf K., Pasmans F., Haesebrouck F. and Ducatelle R. (2009). Strategies to control Salmonella in the broiler production chain. World Poult. Sci. J. 65, 367-391.

Vegad J.L. (2004). Poultry Diseases: A Guide to Farmers and Poultry Professionals. CBS Publishers and Distributors Pvt., New Delhi, India.

Wallace R.J., Oleszek W., Franz C., Hahn I., Baser K.H.C., Mathe A. and Teichmann K. (2010). Dietary plant bioactives for poultry health and productivity. Br. Poult. Sci. 51, 461-487.

Wang H., Gong J., Wang W., Long Y., Fu X., Fu Y., Qian W. and Hou X. (2014). Are there any different effects of Bifidobacterium, Lactobacillus and Streptococcus on intestinal sensation, barrier function and intestinal immunity in PI-IBS mouse model? PLoS One. 9, e90153.

Willis W.L., Isihuemhen O.S., Hurley S. and Ohimain E.I. (2011). Effect of phase feeding supplemental fungus myceliated grain on oocyst excretion and performance of broiler chickens. Int. J. Poult. Sci. 10, 1-3.

Yadav H., Jain S. and Sinha P.R. (2008). Oral administration of dahi containing probiotic Lactobacillus acidophilus and Lactobacillus casei delayed the progression of streptozotocin-induced diabetes in rats. J. Dairy Res. 75, 189-195.

Yadav H., Lee J.H., Lloyd J., Walter P. and Rane S.G. (2013). Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion. J. Biol. Chem. 288, 25088-25097.

Yi H., Hwang K.T., Regenstein J.M. and Shin S.W. (2014). Fatty acid composition and sensory characteristics of eggs obtained from hens fed flaxseed oil, dried whitebait and/or fructo-oligosaccharide. Asian-Australasian J. Anim. Sci. 27, 1026-1034.