A 2012 survey of the US broiler industry to determine and rank production challenges indicated that gut health management was paramount in the minds of those involved with live production (23). This is not surprising since intestinal integrity determines feed efficiency, the most important economic driver of the meat industry. Since then, some significant changes in the industry have sharpened the focus on managing intestinal health.
The Poultry industry is experiencing a particularly profitable period. Over the last twelve months, a nationwide shortage of pork, beef and chicken has induced a significant strengthening in the price of meat and this has coincided with a fall in the price of corn, the primary ingredient in US animal diets (35). While this would normally ease focus on the intensity of intestinal health management, this has not been the case because the status quo of traditional bacterial and protozoal enteropathy control strategies have been concomitantly been shattered by three occurrences. Firstly, the inference that the prevalence of gangrenous dermatitis is associated with the use of ionophores (46), secondly, the voluntary removal of 3-nitro from broiler feed in 2012 and thirdly, a recent statement of intent by a leading fast food chain to only sell chicken meat raised without in-feed antimicrobials within the next five years (5).
FROM INTESTINAL-FLORA TO HOUSEFLORA
Although poultry meat production systems are all-in-all-out in nature, they are, from a gut flora perspective, a continuous system. Members of the gut microbial community surviving in the house environment are carried over from one cycle to the next and thus serve as the “seed stock” for the gut flora of the next placement (33). While in-feed antibiotics can alter the gut flora within a couple of weeks, it takes several grow-out cycles to change the house (litter) flora (3, 29, 33, 48, 49). This is by no means a new concept, both rotation and shuttle programs have been used for decades to avoid the lack of response to in-feed antibiotics following their persistent use.
The realization that even minor changes in intestinal microbial community composition can affect long term productivity through incremental displacement and replacement of the house flora has highlighted the significance of microbial community management (40). Attention to detail is more critical than ever. The efficiency of nutrient assimilation hinges on the early establishment and maintenance of a favorable gut lumen environment. In a drug free production system the emphasis shifts from fighting the unfavorable organisms with antibiotics to nurturing the favorable organisms; working with nature to ensure a favorable and stable intestinal ecology. In its simplest format this involves: seeding the gut with favorable intestinal microbiota, feeding these organisms to ensure that they rapidly dominate the intestinal microbiota and weeding out the unfavorable organisms.
SEEDING THE GUT WITH FAVORABLE ORGANISMS
The first organisms to colonize the gut direct the evolution and composition of the climax flora by creating the microenvironment necessary for complex microbial community development (27). Colonization of the gut with pioneer bacteria species, that are able to modulate expression of genes in the gut epithelia to optimize nutrient assimilation and create favorable conditions for establishment of a stable and beneficial climax flora, should be the starting point of any gut health management program (21, 27). In addition, competitive exclusion has long been recognized as a means of preventing pathogen colonization of the intestinal tract and probiotics have recently been shown to suppress colonization of the intestine with Brachyspira pilosicoli (34), Clostridium perfringens (42), Campylobacter jejuni (45), and Salmonella enteritidis (55). Since the first organisms to gain access to the hatchling gut originate from the parent, steps to control gut health should start at the parent flock level. Vertical transmission of gut inhabitants (from parent to offspring) can be transovarial (inside the egg) or as a result of contamination during oviposition (28, 30, 41)
In the artificially clean hatchery environment, even low doses of beneficial bacteria can significantly improve resistance to pathogen colonization, and artificial seeding of the gut at an early age has been shown to be beneficial (6, 15-17, 19, 24-26, 32, 36, 38).
FEEDING THE FAVORABLE ORGANISMS
In addition to seeding the gut with the correct pioneer species, it is crucial to enhance their ability to proliferate, compete and colonize, so as to avoid pathogen proliferation. Weak organic acids can be used to change gut flora community structure (39, 43). As weak proton donors, they are able to escape inactivation in the upper intestinal tract (proventriculus and gizzard), while their presence in the small intestine modifies microbial community composition (44). Endogenous short chain fatty acids have a microbiota stabilizing effect and butyrate in particular has been shown to stimulate the production of host defence peptides (β-Defensins and Cathelicidins) (54). By providing a competitive advantage to the acid tolerant organisms such as the Lactobacilli and a competitive disadvantage to the acid intolerant organisms like the Clostridia, it is possible to guide the development microbiota composition (13, 44). Such manipulation of the microbiota has both short and long term implications.
Unfavorable organisms are in general much more competitive in the environment of the lower intestinal tract and their replication is normally kept in check by intense competition for a limited source of nutrients (58). Any factor that reduces digestion efficiency in the upper gastrointestinal tract, or increases nitrogen turnover in chickens, could potentially alter cecal ecology. Urine (uric acid) and feed (undigested protein) nitrogen are used by cecal flora to synthesize microbial protein (4), a process that unfortunately yields toxic metabolites and causes dysbacteriosis (12, 14, 22). In contrast, volatile fatty acids (VFA) formed during carbohydrate degradation, have antibacterial activity which has a stabilizing effect on the cecal ecology (2, 7, 8, 13, 53, 56, 57). Since cecal ecology is adversely affected by protein maldigestion, exogenous enzymes designed for protein ingredients can be used to help stabilize cecal flora communities. The amount of protein nitrogen reaching the ceca can be further reduced if nutrient credit allocation permits a reduction in dietary protein (47).
WEEDING OUT THE UNFAVORABLE ORGANISMS
The traditional approach to weeding out unfavorable organisms has been through the addition of a low level of antibiotic to the diet. The consumer has, rightly or wrongly, made the link between the emergence of antibiotic resistant strains of human pathogens and antibiotic use in animal agriculture. This approach to intestinal microbiota management is rapidly falling from grace. While antimicrobial substitutes such as essential oils and in-feed bacillus probiotics have become popular, the long term sustainability/future of these products may come into question; they are after all antibiotics by a different name. Alternatives that utilize a different mechanism of action which avoids the negative aspects of low dose antimicrobial use is, from most perspectives, a more suitable solution.
As colonization proceeds, organisms attach to one another and the epithelium by a series of fibrils, to form a tightly adherent mat over the gut surface (20). Pathogens are thereby precluded access to the epithelial surface and their ability to colonize is compromised by a process of competitive exclusion (37). Microbe attachment to host cell docking sites on the intestinal epithelium is dependent on surface molecule structure and is the pivotal first step in the colonisation and infection of the gut (20, 31, 50, 52) . Since several gut pathogens recognise and attach to specific gut epithelia glycoproteins, products that mimic these docking sites are also useful in preventing attachment and reducing the risk of pathogen colonization (1, 18, 20, 51).
Pathogen induced inflammation of the gut lining stimulates mucus secretion, increased paracellular permeability, and accelerated feed passage (peristalsis) (10, 11). The cascade of events that follows is self-perpetuating. Increased permeability enhances toxin and agent penetration, which in turn stimulates inflammation, and the resulting increase in mucus production attracts mucolytic species such as Clostridium perfringens, which produce tissue damaging cytotoxins (9, 10); a vicious cycle ensues.
Strategies to improve gut health in commercial operations need to be cost effective, sustainable, farm specific and holistic. Intervention / product selection needs to be science based but practical and each intervention must address the specific objective for its inclusion. Efforts to nurture and stabilize a favorable intestinal microbiota with alternative approaches have shown promise in addressing the negative impact of in-feed antibiotic removal and use. While there are several opportunities and product options to achieve this, there are three simple interventions that have demonstrated particular promise. By seeding the hatchling gut with favorable organisms, feeding these organisms with an appropriate organic acid, and weeding out the unfavorable competitors with a type-1 fimbriae blocker, it is possible to improve performance by accelerating the evolution of, and maintain the stability of, a favorable intestinal microbiota.
Presented at the 64th Western Poultry Disease Conference 2015.
1. Abgottspon, D., and B. Ernst. In vivo evaluation of FimH antagonists - a novel class of antimicrobials for the treatment of urinary tract infection. Chimia 66:166-169. 2012.
2. Annison, E. F., K. J. Hill, and R. Kenworthy. Volatile fatty acids in the digestive tract of the fowl. Br J Nutr 22:207-216. 1968.
3. Avellaneda, G., J. Lu, T. Liu, M. Lee, C. Holfacre, and J. Maurer. The Impact Of GrowthPromoting Antibiotics On Total Poultry Microbiota As Well As Enterococcus Population Present On Poultry Carcass. In: Congress of the World Veterinary Poultry Association July Program and Abstracts. Poultry Disease Research Center, University of Georgia. 2003.
4. Bjornhag, D., and I. Sperber. Transport of various food components through the digestive tract of turkeys, geese and guinea fowl. Swedish Journal of Agricultural Science 7:57-66. 1977.
5. Cathy, D. Chick-fil-A to Serve AntibioticFree Chicken In: Press Release. P. Room, ed. Chickfil-A, Chick-fil-A Website. 2014.
6. Chaing, S., and W. Hseih. Effect of directfed microorganisms on broiler growth performanceand litter ammonia level. Asian Australian Journal of Animal Science 1995:159-162. 1995.
7. Cherrington, C. A., M. Hinton, and I. Chopra. Effect of short-chain organic acids on macromolecular synthesis in Escherichia coli. J Appl Bacteriol 68:69-74. 1990.
8. Cherrington, C. A., M. Hinton, G. C. Mead, and I. Chopra. Organic acids: chemistry, antibacterial activity and practical applications. Adv Microb Physiol 32:87-108. 1991.
9. Collier, C. T., C. L. Hofacre, A. M. Payne, D. B. Anderson, P. Kaiser, R. I. Mackie, and H. R. Gaskins. Coccidia-induced mucogenesis promotes the onset of necrotic enteritis by supporting Clostridium perfringens growth. Vet Immunol Immunopathol 122:104-115. 2008.
10. Collier, C. T., J. D. van der Klis, B. Deplancke, D. B. Anderson, and H. R. Gaskins. Effects of tylosin on bacterial mucolysis, Clostridium perfringens colonization, and intestinal barrier function in a chick model of necrotic enteritis. Antimicrobial Agents Chemotherapy 47:3311-3317. 2003.
11. Cooper, B. T. Small intestinal permeability in clinical practice. J Clin Gastroenterol 6:499-501. 1984.
12. Craven, S. E. Colonization of the intestinal tract by Clostridium perfringens and fecal shedding in diet-stressed and unstressed broiler chickens. Poult Sci 79:843-849. 2000.
13. Davidson, P. Chemical preservatives and natural antimicrobial compounds. In: Food Microbiology - Fundamentals and Frontiers, 2nd ed. M. Doyle, L. Beuchat and T. Montville, eds. American Society for Microbiology, Washington, DC. pp 593-627. 2001.
14. Drew, M., N. Syed, B. Goldade, B. Laarveld, and A. Van Kessel. Effects of dietary protein source and level on intestinal populations of Clostridium perfringens in broiler chickens. Poultry Science 83:414-420. 2004.
15. Edens, F. W., C. R. Parkhurst, I. A. Casas, and W. J. Dobrogosz. Principles of ex ovo competitive exclusion and in ovo administration of Lactobacillus reuteri. Poult Sci 76:179-196. 1997.
16. England, J., S. Watkins, E. Saleh, P. Waldroup, I. Casas, and D. Burnham. Effects of Lactobacillus reuteri on live performance and intestinal development of male turkeys. Journal of Applied Poultry Research 5:311-324. 1996.
17. Fernandez, F., M. Hinton, and B. Van Gils. Dietary mannan-oligosaccharides and their effect on chicken caecal microflora in relation to Salmonella Enteritidis colonization. Avian Pathology 31:49-58. 2002.
18. Finucane, M., K. A. Dawson, P. Spring, and K. E. Newman. Effects of Mannanoligosaccharide and BMD on Gut Microflora of Turkey Poults. Poultry Sci. 78 (Suppl. 1):77. 1999.
19. Fukata, T., Y. Hadate, E. Baba, and A. Arakawa. Influence of bacteria on Clostridium perfringens infections in young chickens. Avian Dis 35:224-227. 1991.
20. Giron, J. A., A. G. Torres, E. Freer, and J. B. Kaper. The flagella of enteropathogenic Escherichia coli mediate adherence to epithelial cells. Mol Microbiol 44:361-379. 2002.
21. Guarner, F., and J. R. Malagelada. Gut flora in health and disease. Lancet 361:512-519. 2003.
22. Hamer, H. M., D. Jonkers, K. Venema, S. Vanhoutvin, F. J. Troost, and R. J. Brummer. Review article: the role of butyrate on colonic function. Alimentary pharmacology & therapeutics 27:104- 119. 2008.
23. Hofacre, C. Southeast region Health Update. In: 47th National Meeting on Poultry Health, Processing and Live Production. Clarion Resort Fontainebleau Hotel, Ocean City, MD. 2012.
24. Hofacre, C., T. Beacorn, S. Collett, and G. Mathis. Using competitive Exclusion, MannanOligosaccharide and other Intestinal Products to Control Necrotic Enteritis. J.Appl.Poultry Res. 12:60 - 64. 2003.
25. Hofacre, C. L., R. Froyman, B. Gautrias, B. George, M. A. Goodwin, and J. Brown. Use of Aviguard and other intestinal bioproducts in experimental Clostridium perfringens-associated necrotizing enteritis in broiler chickens. Avian Dis 42:579-584. 1998.
26. Hofacre, C. L. L., M.D., and Maurer, J.J. Enhancing Microflora and its Effects of Clostridium. 2003 37th National Meeting on Poultry Health A Processing. October 9-11th, Ocean City Maryland.:106-108. 2003.
27. Hooper, L. V., and J. I. Gordon. Commensal host-bacterial relationships in the gut. Science 292:1115-1118. 2001.
28. Humphrey, T. J. Contamination of egg shell and contents with Salmonella enteritidis: a review. Int J Food Microbiol 21:31-40. 1994.
29. Idris, U., J. I. Lu, M. Lee, S. Sanchez, C. Hofacre, and J. Maurer. Factors Affecting Epidemiology Of Antibiotic-Resistant Campylobacter Jejuni And Campylobarcter Coli. In: Program and Abstracts, Congress of the World Veterinary Poultry Association. 2003.
30. Inoue, R., and K. Ushida. Vertical and horizontal transmission of intestinal commensal bacteria in the rat model. FEMS microbiology ecology 46:213-219. 2003.
31. Kelly, D., J. I. Campbell, T. P. King, G. Grant, E. A. Jansson, A. G. Coutts, S. Pettersson, and S. Conway. Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclearcytoplasmic shuttling of PPAR-gamma and RelA. Nat Immunol 5:104-112. 2004.
32. La Ragione, R. M., A. Narbad, M. J. Gasson, and M. J. Woodward. In vivo characterization of Lactobacillus johnsonii FI9785 for use as a defined competitive exclusion agent against bacterial pathogens in poultry. Lett Appl Microbiol 38:197-205. 2004.
33. Lilijebjelke, K., C. Hofacre, Liu Tongrui, and J. Maurer. Molecular Epidemiology of Salmonella on Poultry Farms In NE Georgia. Program and Abstracts, Congress of the World Veterinary Poultry Association. 2003.
34. Mappley, L. J., M. A. Tchorzewska, A. Nunez, M. J. Woodward, P. M. Bramley, and R. M. La Ragione. Oral treatment of chickens with Lactobacillus reuteri LM1 reduces Brachyspira pilosicoli-induced pathology. Journal of medical microbiology 62:287-296. 2013.
35. Mathews, K. Recent Rains Benefit Livestock and Poultry. In. USDA-ERS, ed. p 8. 2014.
36. Mohan, B., R. Kadirvel, A. Natarajan, and B. M. Effect of probiotic supplementation on growth, nitrogen utilization and serum cholesterol in broilers. British Poultry Science 37. 1996.
37. Nurmi, E., and M. Rantala. New aspects of Salmonella infection in broiler production. Nature 241:210-211. 1973.
38. Owings, W., D. Reynolds, R. Hasiak, and P. Ferket. Influence of dietary supplementation with Streptococcus faecium M-74 on broiler body weigt, feed conversio, carcass characteristics and intestinal microbial colonization. Poultry Science 69:1257- 1264. 1990.
39. Partanen, K., and Z. Mroz. Nutrition Research Reviews. 12:117-145. 1999.
40. Pedroso, A. A., A. L. Hurley-Bacon, A. S. Zedek, T. W. Kwan, A. P. Jordan, G. Avellaneda, C. L. Hofacre, B. B. Oakley, S. R. Collett, J. J. Maurer, and M. D. Lee. Can probiotics improve the environmental microbiome and resistome of commercial poultry production? International journal of environmental research and public health 10:4534- 4559. 2013.
41. Pedroso, A. A., J. J. Maurer, D. Dlugolenski, and M. D. Lee. Embryonic chicks may possess an intestinal bacterial community within the egg. In: American Society for Microbiology General 108th Meeting. Boston. 2008.
42. Rahimi, S., S. Kathariou, J. L. Grimes, and R. M. Siletzky. Effect of direct-fed microbials on performance and Clostridium perfringens colonization of turkey poults. Poult Sci 90:2656- 2662. 2011.
43. Ravindran, V., and E. Kornegay. Acidification of weaner pig diets: a review. Journal of Science Food and Agriculture 62:313-322. 1993.
44. Ricke, S. C. Perspectives on the use of organic acids and short chain fatty acids as antimicrobials. Poult Sci 82:632-639. 2003.
45. Santini, C., L. , F. Baffoni, M. Gaggia, R. Granata, D. Gasbarri, Di Gioia, and B. Biavati. Characterization of probiotic strains: an application as feed additives in poultry against Campylobacter jejuni. International Journal of. Food Microbiology 141:Suppl 1:98-108. . 2010.
46. Schaeffer, J. L., K. A. Ameiss, G. D. Ritter, and R. M. Poston. Comparison of Two Experimental Coccidiosis Vaccine Formulations When Administered to Commercial Broilers Raised in High or Low Clostridial Challenge Conditions: Growout and Performance Outcomes. In: American Veterinary Medical Association Annual Convention. Georgia World Congress Center 2010.
47. Schang, M. J., and J. O. Azacona. Natural enzyme applications to optimize animal performance. In: Nutritional Biotechnology In The Feed and Food Industries Proceedings of Alltech's 20th Annual Symposium. T. P. Lyons and K. A. Jacques, eds. Nottingham University Press, Nicholasville, KY. 2003.
48. Schildknect, E., L. Rakebrand, L. Jensen, and Skinner. Changes In Anticoccidial Sensitivity Profiles Of Coccidia From Broiler Chickens Raised On Built-Up Litter For Eight Production Cycles Following A Coccidiosis Challenge. In: International Poultry Scientific Forum Abstracts. p 10. 2003.
49. Schildknect, E., L. Rakebrand, L. Jensen, and Skinner. Changes In Live Performance Of Broiler Chickens Raised On Built-Up Litter For Eight Production Cycles Following A Coccidiosis. In: International Poultry Scientific Forum Abstracts. Atlanta, Georgia. 2003.
50. Sharon, N., and H. Lis. Carbohydrates in cell recognition. Sci Am 268:82-89. 1993.
51. Spring, P. Effects of mannanoligosaccharide on different caecal parameters and on the attachment of enteric pathogens in poultry. In. Swiss Fed. Inst. Technology, Zurich. 1996.
52. Stavric, S., T. Gleeson, B. Blanchfield, and H. Pivnick. Effect of environmental temperature on the susceptibility of young chickens to Salmonella typhimurium. Australian Veterinary Journal 55:413. 1987.
53. Sudo, S., and G. Duke. Kinetics of absorption of volatile fatty acids from the ceca of domestic turkeys. Comp. Biochem. Physiol. 67:231- 237. 1980.
54. Sunkara, L. T., M. Achanta, N. B. Schreiber, Y. R. Bommineni, G. Dai, W. Jiang, S. Lamont, H. S. Lillehoj, A. Beker, R. G. Teeter, and G. Zhang. Butyrate enhances disease resistance of chickens by inducing antimicrobial host defense peptide gene expression. PloS one 6:e27225. 2011.
55. Thirabunyanon, M., and N. Thongwittaya. Protection activity of a novel probiotic strain of Bacillus subtilis against Salmonella Enteritidis infection. Res Vet Sci 93:74-81. 2012.
56. Van Immerseel, F., J. De Buck, F. Pasmans, P. Velge, E. Bottreau, V. Fievez, F. Haesebrouck, and R. Ducatelle. Invasion of Salmonella enteritidis in avian intestinal epithelial cells in vitro is influenced by short-chain fatty acids. Int J Food Microbiol 85:237-248. 2003.
57. Van Immerseel, F., J. B. Russell, M. D. Flythe, I. Gantois, L. Timbermont, F. Pasmans, F. Haesebrouck, and R. Ducatelle. The use of organic acids to combat Salmonella in poultry: a mechanistic explanation of the efficacy. Avian Pathology 35:182- 188. 2006.
58. Zinser, E. R., and R. Kolter. Escherichia coli evolution during stationary phase. Research Microbiology 155:328-336. 2004.