Mining chicken ileal microbiota for immunomodulatory ... - Nature.com

Abstract

The gut microbiota makes important contributions to host immune system development and resistance to pathogen infections, especially during early life. However, studies addressing the immunomodulatory functions of gut microbial individuals or populations are limited. In this study, we explore the systemic impact of the ileal microbiota on immune cell development and function of chickens and identify the members of the microbiota involved in immune system modulation. We initially used a time-series design with six time points to prove that ileal microbiota at different succession stages is intimately connected to immune cell maturation. Antibiotics perturbed the microbiota succession and negatively affected immune development, whereas early exposure to the ileal commensal microbiota from more mature birds promoted immune cell development and facilitated pathogen elimination after Salmonella Typhimurium infection, illustrating that early colonization of gut microbiota is an important driver of immune development. Five bacterial strains, Blautia coccoides, Bacteroides xylanisolvens, Fournierella sp002159185, Romboutsia lituseburensis, and Megamonas funiformis, which are closely related to the immune system development of broiler chickens, were then screened out and validated for their immunomodulatory properties. Our results provide insight into poultry immune system–microbiota interactions and also establish a foundation for targeted immunological interventions aiming to combat infectious diseases and promote poultry health and production.

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Fig. 1: Overview of experiment design.

Fig. 2: Temporal and spatial development of ileum microbiota in broiler chickens.

Fig. 3: Sequential waves of immune cell expansion after birth.

Fig. 4: Interaction between bacteria and the proportion of immune cells.

Fig. 5: The antibiotic chlortetracycline interferes with the development of ileum microbiota and immune cells.

Fig. 6: Early exposure to ileal commensal microbiota from more mature individuals influences the immune cell composition of chickens.

Fig. 7: Microbiota transplantation enhances the resistance to Salmonella Typhimurium infection of broiler chickens.

Fig. 8: Immunomodulatory properties of five bacterial strains.

Data availability

The raw 16S rRNA gene sequencing data of luminal microbiota from the antibiotic-untreated broiler chickens were obtained from NCBI BioProject PRJNA817429 (unpublished data from our own laboratory), and additional raw 16S rRNA gene sequencing data have been deposited in NCBI BioProject PRJNA904673. The genome data have been deposited in NCBI BioProject PRJNA903494 and PRJNA902159. The transcriptome data have been deposited in NCBI BioProject PRJNA904665. Raw datasets used for multicolor flow cytometry and qRT-PCR are available on FigShare (https://doi.org/10.6084/m9.figshare.21825042).

References

1. Skarp CPA, Hänninen ML, Rautelin HIK. Campylobacteriosis: the role of poultry meat. Clin Microbiol Infect. 2016;22:103–9.

   Article  CAS  PubMed  Google Scholar 

2. Qi J, Li X, Zhang W, Wang H, Zhou G, Xu X. Influence of stewing time on the texture, ultrastructure and in vitro digestibility of meat from the yellow-feathered chicken breed. Anim Sci J. 2018;89:474–82.

   Article  CAS  PubMed  Google Scholar 

3. Sedeik ME, El-Shall NA, Awad AM, Abd El-Hack ME, Alowaimer AN, Swelum AA. Comparative evaluation of HVT-IBD vector, immune complex, and live IBD vaccines against vvIBDV in commercial broiler chickens with high maternally derived antibodies. Animals. 2019;9:72.

   Article  PubMed  PubMed Central  Google Scholar 

4. El-Shall NA, Shewita RS, Abd El-Hack ME, AlKahtane A, Alarifi S, Alkahtani S, et al. Effect of essential oils on the immune response to some viral vaccines in broiler chickens, with special reference to Newcastle disease virus. Poult Sci. 2020;99:2944–54.

   Article  CAS  PubMed  PubMed Central  Google Scholar 

5. Maron DF, Smith TJS, Nachman KE. Restrictions on antimicrobial use in food animal production: an international regulatory and economic survey. Glob Health. 2013;9:48.

   Article  Google Scholar 

6. Favier CF, de Vos WM, Akkermans AD. Development of bacterial and bifidobacterial communities in feces of newborn babies. Anaerobe. 2003;9:219–29.

   Article  PubMed  Google Scholar 

7. Wang S, Ryan CA, Boyaval P, Dempsey EM, Ross RP, Stanton C. Maternal vertical transmission affecting early-life microbiota development. Trends Microbiol. 2020;28:28–45.

   Article  CAS  PubMed  Google Scholar 

8. Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell. 2005;122:107–18.

   Article  CAS  PubMed  Google Scholar 

9. Baumler AJ, Sperandio V. Interactions between the microbiota and pathogenic bacteria in the gut. Nature. 2016;535:85–93.

   Article  CAS  PubMed  PubMed Central  Google Scholar 

10. Honda K, Littman DR. The microbiota in adaptive immune homeostasis and disease. Nature. 2016;535:75–84.

    Article  CAS  PubMed  Google Scholar 

11. Kim YG, Sakamoto K, Seo SU, Pickard JM, Gillilland MG 3rd, Pudlo NA, et al. Neonatal acquisition of Clostridia species protects against colonization by bacterial pathogens. Science. 2017;356:315–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

12. Chung H, Pamp SJ, Hill JA, Surana NK, Edelman SM, Troy EB, et al. Gut immune maturation depends on colonization with a host-specific microbiota. Cell. 2012;149:1578–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

13. Ostman S, Rask C, Wold AE, Hultkrantz S, Telemo E. Impaired regulatory T cell function in germ-free mice. Eur J Immunol. 2006;36:2336–46.

    Article  PubMed  Google Scholar 

14. Tastan C, Karhan E, Zhou W, Fleming E, Voigt AY, Yao X, et al. Tuning of human MAIT cell activation by commensal bacteria species and MR1-dependent T-cell presentation. Mucosal Immunol. 2018;11:1591–605.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

15. Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009;136:485–98.

    Article  Google Scholar 

16. Atarashi K, Tanoue T, Oshima K, Suda W, Nagano Y, Nishikawa H, et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature. 2013;500:232–6.

    Article  CAS  PubMed  Google Scholar 

17. Verma R, Lee C, Jeun EJ, Yi J, Kim KS, Ghosh A, et al. Cell surface polysaccharides of Bifidobacterium bifidum induce the generation of Foxp3⁺ regulatory T cells. Sci Immunol. 2018;3:eaat6975.

    Article  PubMed  Google Scholar 

18. Dibner JJ, Knight CD, Kitchell ML, Atwell CA, Downs AC, Ivey FJ. Early feeding and development of the immune system in neonatal poultry. J Appl Poult Res. 1998;7:425–36.

    Article  CAS  Google Scholar 

19. Khadem A, Soler L, Everaert N, Niewold TA. Growth promotion in broilers by both oxytetracycline and Macleaya cordata extract is based on their anti-inflammatory properties. Br J Nutr. 2014;112:1110–8.

    Article  CAS  PubMed  Google Scholar 

20. Pourabedin M, Guan L, Zhao X. Xylo-oligosaccharides and virginiamycin differentially modulate gut microbial composition in chickens. Microbiome. 2015;3:15.

    Article  PubMed  PubMed Central  Google Scholar 

21. Varmuzova K, Kubasova T, Davidova-Gerzova L, Sisak F, Havlickova H, Sebkova A, et al. Composition of gut microbiota influences resistance of newly hatched chickens to Salmonella Enteritidis infection. Front Microbiol. 2016;7:957.

    Article  PubMed  PubMed Central  Google Scholar 

22. Zhang X, Akhtar M, Chen Y, Ma Z, Liang Y, Shi D, et al. Chicken jejunal microbiota improves growth performance by mitigating intestinal inflammation. Microbiome. 2022;10:107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

23. Freeman TC, Ivens A, Baillie JK, Beraldi D, Barnett MW, Dorward D, et al. A gene expression atlas of the domestic pig. BMC Biol. 2012;10:90.

    Article  PubMed  PubMed Central  Google Scholar 

24. Mach N, Berri M, Esquerré D, Chevaleyre C, Lemonnier G, Billon Y, et al. Extensive expression differences along porcine small intestine evidenced by transcriptome sequencing. PLoS ONE. 2014;9:e88515.

    Article  PubMed  PubMed Central  Google Scholar 

25. Lu J, Idris U, Harmon B, Hofacre C, Maurer JJ, Lee MD. Diversity and succession of the intestinal bacterial community of the maturing broiler chicken. Appl Environ Microbiol. 2003;69:6816–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

26. Oakley BB, Buhr RJ, Ritz CW, Kiepper BH, Berrang ME, Seal BS, et al. Successional changes in the chicken cecal microbiome during 42 days of growth are independent of organic acid feed additives. BMC Vet Res. 2014;10:282.

    Article  PubMed  PubMed Central  Google Scholar 

27. Oakley BB, Kogut MH. Spatial and temporal changes in the broiler chicken cecal and fecal microbiomes and correlations of bacterial taxa with cytokine gene expression. Front Vet Sci. 2016;3:11.

    Article  PubMed  PubMed Central  Google Scholar 

28. Hu J, Chen L, Tang Y, Xie C, Xu B, Shi M, et al. Standardized preparation for fecal microbiota transplantation in pigs. Front Microbiol. 2018;9:1328.

    Article  PubMed  PubMed Central  Google Scholar 

29. Withanage GS, Kaiser P, Wigley P, Powers C, Mastroeni P, Brooks H, et al. Rapid expression of chemokines and proinflammatory cytokines in newly hatched chickens infected with Salmonella enterica serovar typhimurium. Infect Immun. 2004;72:2152–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

30. Beal RK, Wigley P, Powers C, Hulme SD, Barrow PA, Smith AL. Age at primary infection with Salmonella enterica serovar Typhimurium in the chicken influences persistence of infection and subsequent immunity to re-challenge. Vet Immunol Immunopathol. 2004;100:151–64.

    Article  CAS  PubMed  Google Scholar 

31. Beal RK, Powers C, Wigley P, Barrow PA, Kaiser P, Smith AL. A strong antigen-specific T-cell response is associated with age and genetically dependent resistance to avian enteric Salmonellosis. Infect Immun. 2005;73:7509–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

32. Kogut MH, Genovese KJ, He HQ, Swaggerty CL, Jiang YW. Modulation of chicken intestinal immune gene expression by small cationic peptides as feed additives during the first week posthatch. Clin Vaccin Immunol. 2013;20:1440–8.

    Article  CAS  Google Scholar 

33. Hoszowski A, Truszczynski M. Prevention of Salmonella typhimurium caecal colonisation by different preparations for competitive exclusion. Comp Immunol Microbiol Infect Dis. 1997;20:111–7.

    Article  CAS  PubMed  Google Scholar 

34. Kramer J, Visscher AH, Wagenaar JA, Boonstra-Blom AG, Jeurissen SH. Characterization of the innate and adaptive immunity to Salmonella enteritidis PT1 infection in four broiler lines. Vet Immunol Immunopathol. 2001;79:219–33.

    Article  CAS  PubMed  Google Scholar 

35. Kogut MH, Genovese KJ, He H, Li MA, Jiang YW. The effects of the BT/TAMUS 2032 cationic peptides on innate immunity and susceptibility of young chickens to extraintestinal Salmonella enterica serovar Enteritidis infection. Int Immunopharmacol. 2007;7:912–9.

    Article  CAS  PubMed  Google Scholar 

36. Crippen TL, Bischoff KM, Lowry VK, Kogut MH. rP33 activates bacterial killing by chicken peripheral blood heterophils. J Food Prot. 2003;66:787–92.

    Article  PubMed  Google Scholar 

37. Rychlik I, Elsheimer-Matulova M, Kyrova K. Gene expression in the chicken caecum in response to infections with non-typhoid Salmonella. Vet Res. 2014;45:119.

    Article  PubMed  PubMed Central  Google Scholar 

38. Kashiwagi M, Hosoi J, Lai J-F, Brissette J, Ziegler SF, Morgan BA, et al. Direct control of regulatory T cells by keratinocytes. Nat Immunol. 2017;18:334–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

39. Atarashi K, Tanoue T, Ando M, Kamada N, Nagano Y, Narushima S, et al. Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell. 2015;163:367–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

40. Lécuyer E, Rakotobe S, Lengliné-Garnier H, Lebreton C, Picard M, Juste C, et al. Segmented filamentous bacterium uses secondary and tertiary lymphoid tissues to induce gut IgA and specific T helper 17 cell responses. Immunity. 2014;40:608–20.

    Article  PubMed  Google Scholar 

41. Paramsothy S, Kamm MA, Kaakoush NO, Walsh AJ, van den Bogaerde J, Samuel D, et al. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet. 2017;389:1218–28.

    Article  PubMed  Google Scholar 

42. Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science. 2011;331:337–41.

    Article  CAS  PubMed  Google Scholar 

43. Quandt D, Rothe K, Baerwald C, Rossol M. GPRC6A mediates Alum-induced Nlrp3 inflammasome activation but limits Th2 type antibody responses. Sci Rep. 2015;5:16719.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

44. Blander JM. The comings and goings of MHC class I molecules herald a new dawn in cross-presentation. Immunol Rev. 2016;272:65–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

45. Shirakawa K, Endo J, Kataoka M, Katsumata Y, Yoshida N, Yamamoto T, et al. IL (Interleukin)-10-STAT3-Galectin-3 axis is essential for osteopontin-producing reparative macrophage polarization after myocardial infarction. Circulation. 2018;138:2021–35.

    Article  CAS  PubMed  Google Scholar 

46. Hörhold F, Eisel D, Oswald M, Kolte A, Röll D, Osen W, et al. Reprogramming of macrophages employing gene regulatory and metabolic network models. PLoS Comput Biol. 2020;16:e1007657.

    Article  PubMed  PubMed Central  Google Scholar 

47. Dillmann C, Mora J, Olesch C, Brüne B, Weigert A. S1PR4 is required for plasmacytoid dendritic cell differentiation. Biol Chem. 2015;396:775–82.

    Article  CAS  ...