Effect of host genotype and Eimeria acervulina infection on the metabolome of meat-type chickens

Autoři: Samuel E. Aggrey aff001;  Marie C. Milfort aff001;  Alberta L. Fuller aff001;  Jianmin Yuan aff002;  Romdhane Rekaya aff003
Působiště autorů: NutriGenomics Laboratory, Department of Poultry Science, University of Georgia, Athens, Georgia, United States of America aff001;  State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, Peoples Republic of China aff002;  Department of Animal and Dairy Science, University of Georgia, Athens, Georgia, United States of America aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0223417



A study was conducted to identify metabolic biochemical differences between two chicken genotypes infected with Eimeria acervulina and to ascertain the underlying mechanisms for these metabolic alterations and to further delineate genotype-specific effects during merozoite formation and oocyst shedding.


Fourteen day old chicks of an unimproved (ACRB) and improved (COBB) genotype were orally infected with 2.5 x 105 sporulated E. acervulina oocysts. At 4 and 6 day-post infection, 5 birds from each treatment group and their controls were bled for serum. Global metabolomic profiles were assessed using ultra performance liquid chromatography/tandem mass spectrometry (metabolon, Inc.,). Statistical analyses were based on analysis of variance to identify which biochemicals differed significantly between experimental groups. Pathway enrichment analysis was conducted to identify significant pathways associated with response to E. acervulina infection.


A total of 752 metabolites were identified across genotype, treatment and time post infection. Altered fatty acid (FA) metabolism and β-oxidation were identified as dominant metabolic signatures associated with E. acervulina infection. Key metabolite changes in FA metabolism included stearoylcarnitine, palmitoylcarnitine and linoleoylcarnitine. The infection induced changes in nucleotide metabolism and elicited inflammatory reaction as evidenced by changes in thromboxane B2, 12-HHTrE and itaconate.


Serum metabolome of two chicken genotypes infected with E. acervulina demonstrated significant changes that were treatment-, time post-infection- and genotype-dependent. Distinct metabolic signatures were identified in fatty acid, nucleotide, inflammation and oxidative stress biochemicals. Significant microbial associated product alterations are likely to be associated with malabsorption of nutrients during infection.

Klíčová slova:

Birds – Fatty acids – Chickens – Inflammation – Metabolites – Metabolomics – Xenobiotic metabolism – Eimeria


1. Shanmugasundram A, Gonzalez-Galarza FF, Wastling JM, Vasieva O, Jones AR. (2013) Library of Apicomplexan Metabolic Pathways: a manually curated database for metabolic pathways of apicomplexan parasites. Nucleic Acids Res 41(Database issue):D706–13. doi: 10.1093/nar/gks1139 23193253

2. McDougald LR, Fitz-Coy SH (2008) Coccidiosis. In: Saif YM, Fadly AM, Glisson JR, McDougald LR, Nolan LK, Swayne DE, editors. Diseases of Poultry, 12th ed. Ames, IA: Blackwell Publishing Professional pp1068–1085

3. Belli SI, Smith NC, Ferguson DJ (2006) The coccidian oocyst: a tough nut to crack! Trends Parasitol 22:416–423. doi: 10.1016/j.pt.2006.07.004 16859995

4. Joyner LP, Long PL (1974) The specific characters of the Eimeria, with special reference to the coccidia of the fowl. Avian Pathol 3: 145–157. doi: 10.1080/03079457409353827 18777269

5. Ruff MD (1999) Important parasites in poultry production systems. Vet Parasitol 84:337–347. doi: 10.1016/s0304-4017(99)00076-x 10456422

6. Dalloul RA, Lillehoj HS (2005) Recent advances in immunomodulation and vaccination strategies against coccidiosis. Avian Dis 49:1–8. doi: 10.1637/7306-11150R 15839405

7. Shirley MW, Smith AL, Tomley FM (2005) The biology of avian Eimeria with an emphasis on their control by vaccination. Adv Parasitol 60:285–330. doi: 10.1016/S0065-308X(05)60005-X 16230106

8. McDougald LR, Fuller L, Mattiello R (1997) A survey of Coccidia on 43 poultry farms in Argentina. Avian Dis 41:923–929. https://doi.org/10.2307/1592347 9454927

9. Lew AE, Anderson GR, Minchin CM, Jeston PJ, Jorgensen WK (2003) Inter- and intra-strain variation and PCR detection of the internal transcribed spacer 1 (ITS-1) sequences of Australian isolates of Eimeria species from chickens. Vet Parasitol 112:33–50. doi: 10.1016/s0304-4017(02)00393-x 12581583

10. Kumar S, Garg R, Moftah A, Clark EL, Macdonald SE, Chaudhry AS, Sparagano O, Banerjee PS, Kundu K, Tomley FM, Blake DP (2014) An optimised protocol for molecular identification of Eimeria from chickens. Vet Parasitol 199:24–31. doi: 10.1016/j.vetpar.2013.09.026 24138724

11. Tang X, Huang G, Liu X, El-Ashram S, Tao G, Lu C, Suo J, Suo X (2018) Parasitol Res 117:655–664. doi: 10.1007/s00436-017-5683-8 29396674

12. Wishart DS (2016) Emerging applications of metabolomics in drug discovery and precision medicine Nat Rev Drug Discov 473–84. doi: 10.1038/nrd.2016.32 26965202

13. Counts SE, Ikonomovic MD, Mercado N, Vega IE, Mufson EJ (2017) Biomarkers for the Early Detection and Progression of Alzheimer's Disease. Neurotherapeutics 14:35–53. doi: 10.1007/s13311-016-0481-z 27738903

14. Collins KE, Marks HL, Aggrey SE, Lacy MP, Wilson JL (2016) History of the Athens Canadian Random Bred and the Athens Random Bred control populations. Poult Sci 95: 997–1004. doi: 10.3382/ps/pew085 26976904

15. 5m Editor (2008) How the Cobb 500 changed the US Market. [Internet] Available: https://thepoultrysite.com/articles/how-the-cobb-500-changed-the-us-market

16. Dehaven CD, Evans AM, Dai H, Lawton KA (2010) Organization of GC/MS and LC/MS metabolomics data into chemical libraries. J Cheminform 2:9. doi: 10.1186/1758-2946-2-9 20955607

17. DeHaven CD, Evans AM, Hongping D, Lawton KA. Software techniques for enabling high-throughput analysis of metabolomics datasets (2012). In: Roessner U, editor. Metabolomics. Rijeka, Croatia: InTech pp. 167–192

18. Michell MW (2011) Bias of the random forest out-of-bag (OOB) error for certain input parameters. Open J Stat 1: 205–211 https://doi.org/10.4236/ojs.2011.13024

19. Stacklies W, Redestig H, Scholz M, Walther D, Selbig J (2007) pcaMethods-a bioconductor package providing PCA methods for incomplete data. Bioinformatics 23:1164–1167. doi: 10.1093/bioinformatics/btm069 17344241

20. Kolde R (2015) pheatmap: Pretty Heatmaps. R package version 1.0.2 http://cran.r-project.org/web/packages/pheatmap/index.html

21. Luo W and Brouwer C (2013) Pathview: An R/Bioconductor package for pathway-based data integration and visualization. Bioinformatics 29: 830–1831. doi: 10.1093/bioinformatics/btt285 23740750

22. Talebi A, Mulcahy G (2005) Partial protection against Eimeria acervulina and Eimeria tenella induced by synthetic peptide vaccine. Exp Parasitol 110:342–348. doi: 10.1016/j.exppara.2005.03.026 15878770

23. Moraes PO, Andretta I, Cardinal KM, Ceron M, Vilella L, Borille R, Frazzon AP, Frazzon J, Santin E, Ribeiro AML (2019) Effect of functional oils on the immune response of broilers challenged with Eimeria spp. Animal. [Epub ahead of print] doi: 10.1017/S1751731119000600 30955505

24. Djemai S, Mekround A, Jenkins MC (2016). Evaluation of ionophore sensitivity of Eimeria acervulina and Eimeria maxima isolated from the Algerian to Jijel province poultry farms. Vet Parasitol 224:77–81. doi: 10.1016/j.vetpar.2016.04.040 27270394

25. Mathis GF, Washburn KW, McDougald LR (1984). Genetic variability of resistance to Eimeria acervulina and E. tenella in chickens. Theor Appl Genet 68:385–389. doi: 10.1007/BF00254803 24257728

26. Bell DJ (1971) In: Bell DJ and Freeman BM (Editors) Physiology and Biochemistry of the Domestic Fowl. Academic Press, New York, Vol. 2, pp 913–920.

27. Miska KB, Fetterer RH (2017). The mRNA expression of amino acid and sugar transporters, aminopeptidase, as well as the di- and tri-peptide transporter PepT1 in the intestines of Eimeria infected broiler chickens. Poult Sci 96:465–473 doi: 10.3382/ps/pew303 27591271

28. Meyer H, Vitavska O, Wieczorek H (2010). Identification of an animal sucrose transporter. J Cell Sci 124(Pt 12):1984–1991. doi: 10.1242/jcs.082024 21586609

29. Allen PC (1984) Physiological responses of chicken gut tissue to infection with Eimeria acervulina. Avian Dis 28:868–876 6441557

30. Allen PC, Fetterer RH (2002) Interaction of dietary vitamin E with Eimeria maxima infections in chickens. Poult Sci 81: 41–48 doi: 10.1093/ps/81.1.41 11885898

31. Allen PC (1987) Physiological responses of chicken gut tissue to coccidial infection: comparative effects of Eimeria acervulina and Eimeria mitis on mucosal mass, carotenoid content, and brush border enzyme activity. Poult Sci. 66:1306–1315 doi: 10.3382/ps.0661306 3684853

32. Singh SP, Donovan GA (1973) A relationship between coccidiosis and dietary vitamin A levels in chickens. Poult Sci 52: 295–1301 doi: 10.3382/ps.0521295 4773324

33. Fernando MA, McCraw BM (1973) Mucosal morphology and cellular renewal in the intestine of chickens following a single infection of Eimeria acervulina. J Parasitol 59: 493–501 4576141

34. Sharma VD, Fernando MA (1975) Effect of Eimeria acervulina infection on nutrient retention with special reference to fat malabsorption in chickens. Can J Comp Med 39: 146–154 164990

35. Ruff MD, Johnson JK, Dykstra DD, Reid WM (1974) Effect of Eimeria acervulina on intestinal pH in conventional and gnotobiotic chickens. Avian Dis 18: 96–104 4205348

36. Adams C, Vahl HA, Veldman A (1996) Interaction between nutrition and Eimeria acervulina infection in broiler chickens: diet compositions that improve fat digestion during Eimeria acervulina infection. Br J Nutr 75: 875–880 doi: 10.1079/bjn19960193 8774232

37. Webb JP, James AT, Kellock TD (1963) The influence of diet on the quality of faecal fat in patients with and without steatorrhoea. Gut 4: 37–41 doi: 10.1136/gut.4.1.37 13999335

38. Newman JC, Verdin E (2014) β-hydroxybutyrate: much more than a metabolite. Diabetes Res Clin Pract 106:173–181 doi: 10.1016/j.diabres.2014.08.009 25193333

39. Allen PC (1987) Physiological responses of chicken gut tissue to coccidial infection: comparative effects of Eimeria acervulina and Eimeria mitis on mucosal mass, carotenoid content, and brush border enzyme activity. Poult Sci. 66:1306–1315 doi: 10.3382/ps.0661306 3684853

40. Allen PC (1988) The effect of Eimeria acervulina infection on plasma lipids and lipoproteins in young broiler chicks. Vet Parasitol 30:17–30 doi: 10.1016/0304-4017(88)90139-2 3212927

41. Schaefer EJ, Eisenberg S, Levy RI (1978) Lipoprotein aproprotein metabolism. J Lipid Res 19: 667–687 211170

42. Higgs GA, Moncada S, Salmon JA, Seager K (1983) The source of thromboxane and prostaglandins in experimental inflammation. Br J Pharmacol 79:863–8 doi: 10.1111/j.1476-5381.1983.tb10530.x 6652359

43. Wang N, Vendrov KC, Smmons BP, Schuck RN, Stouffer GA, Lee Cr (2018) Urinary 11-dehydro-thromboxane B2 levels are associated with vascular inflammation and prognosis in atherosclerotic cardiovascular disease Prostagladins Other Lipid Mediat 134: 24–31 doi: 10.1016/j.prostaglandins.2017.11.003 29155368

44. Mills EL, Ryan DG, Prag HA, Dikovskaya D, Menon D, Zaslona Z, Jedrychowski MP, Costa ASH, Higgins M, Hams E, Szpyt J, Runtsch MC, King MS, McGouran JF, Fischer R, Kessler BM, McGettrick AF, Hughes MM, Carroll RG, Booty LM, Knatko EV, Meakin PJ, Ashford MLJ, Modis LK, Brunori G, Sévin DC, Fallon PG, Caldwell ST, Kunji ERS, Chouchani ET, Frezza C, Dinkova-Kostova AT, Hartley RC, Murphy MP, O'Neill LA (2018) Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature.:113–117. doi: 10.1038/nature25986 29590092

45. Bordon Y (2018) Itaconate charges down inflammation. Nat Rev Immunol 18:360–361. doi: 10.1038/s41577-018-0016-4 29725119

46. Yu XH, Zhang DW, Zheng XL, Tang CK (2019) Itaconate: an emerging determinant of inflammation in activated macrophages. Immunol Cell Biol 97:134–141. doi: 10.1111/imcb.12218 30428148

47. Barrie N, Manolios N (2017) The endocannabinoid system in pain and inflammation: Its relevance to rheumatic disease. Eur J Rheumatol 4: 210–218 doi: 10.5152/eurjrheum.2017.17025 29164003

48. Burstein SH, Zurier RB (2009) Cannabinoids, endocannabinoids, and related analogs in inflammation. AAPS J 11:109–119. doi: 10.1208/s12248-009-9084-5 19199042

49. Witkamp R (2016) Fatty acids, endocannabinoids and inflammation. Eur J Pharmacol 785:96–107. doi: 10.1016/j.ejphar.2015.08.051 26325095

50. Witkamp R, Meijerink J (2014) The endocannabinoid system: an emerging key player in inflammation Curr Opin Clin Nutr Metab Care 17:130–8. doi: 10.1097/MCO.0000000000000027 24419242

51. Wang Q, Liu D, Song P, Zou MH (2015) Tryptophan-kynurenine pathway is dysregulated in inflammation, and immune activation. Front Biosci (Landmark Ed) 20:1116–1143 doi: 10.2741/4363 25961549

52. Cervenka I, Agudelo LZ, Ruas JL (2017) Kynurenines: Tryptophan's metabolites in exercise, inflammation, and mental health. Science 357: eaaf9794. doi: 10.1126/science.aaf9794 28751584

53. Aggrey SE, Lee J, Karnuah AB, Rekaya R (2014) Transcriptomic analysis of genes in the nitrogen recycling pathway of meat-type chickens divergently selected for feed efficiency. Anim Genet. 45:215–22. doi: 10.1111/age.12098 24330162

54. Pang B, McFaline JL, Burgis NE, Dong M, Taghizadeh K, Sullivan MR, Elmquist CE, Cunningham RP, Dedon PC (2012) Defects in purine nucleotide metabolism lead to substantial incorporation of xanthine and hypoxanthine into DNA and RNA. Proc Natl Acad Sci 109:2319–2324. doi: 10.1073/pnas.1118455109 22308425

55. Wu SH, Shu XO, Milne G, Xiang YB, Zhang X, Cai Q, Fazio S, Linton MF, Chen H, Purdue M, Rothman N, Gao YT, Zheng W, Yang G (2015) Uric acid correlates to oxidation and inflammation in opposite directions in women. Biomarkers 20:225–231. doi: 10.3109/1354750X.2015.1068852 26301880

56. Zhou Y, Zhao M, Pu Z, Xu G, Li X (2018) Relationship between oxidative stress and inflammation in hyperuricemia: Analysis based on asymptomatic young patients with primary hyperuricemia. Medicine (Baltimore) 97:e13108. doi: 10.1097/MD.0000000000013108 30544373

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