Abstract
Background
The gut microbiota influences host performance playing a relevant role in homeostasis and function of the immune system. The aim of the present work was to identify microbial signatures linked to immunity traits and to characterize the contribution of host-genome and gut microbiota to the immunocompetence in healthy pigs.
Results
To achieve this goal, we undertook a combination of network, mixed model and microbial-wide association studies (MWAS) for 21 immunity traits and the relative abundance of gut bacterial communities in 389 pigs genotyped for 70K SNPs. The heritability (h2; proportion of phenotypic variance explained by the host genetics) and microbiability (m2; proportion of variance explained by the microbial composition) showed similar values for most of the analyzed immunity traits, except for both IgM and IgG in plasma that was dominated by the host genetics, and the haptoglobin in serum which was the trait with larger m2 (0.275) compared to h2 (0.138). Results from the MWAS suggested a polymicrobial nature of the immunocompetence in pigs and revealed associations between pigs gut microbiota composition and 15 of the analyzed traits. The lymphocytes phagocytic capacity (quantified as mean fluorescence) and the total number of monocytes in blood were the traits associated with the largest number of taxa (6 taxa). Among the associations identified by MWAS, 30% were confirmed by an information theory network approach. The strongest confirmed associations were between Fibrobacter and phagocytic capacity of lymphocytes (r = 0.37), followed by correlations between Streptococcus and the percentage of phagocytic lymphocytes (r = -0.34) and between Megasphaera and serum concentration of haptoglobin (r = 0.26). In the interaction network, Streptococcus and percentage of phagocytic lymphocytes were the keystone bacterial and immune-trait, respectively.
Conclusions
Overall, our findings reveal an important connection between gut microbiota composition and immunity traits in pigs, and highlight the need to consider both sources of information, host genome and microbial levels, to accurately characterize immunocompetence in pigs.
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Background
The pig industry has a considerable socio-economical value representing around 35% of the total meat produced worldwide [1] and being the most popular meat for consumption [2]. The intensification of pig production coupled with the ban on in-feed use of antibiotics has led to a deterioration of the health status of pig farms. In addition, the current emergence of antibiotic resistance and society demands for healthier products and environmentally responsible livestock systems, has motivated to explore relevant approaches for pig and other livestock breeding programs, to improve robustness and disease resistance [3].
The implementation of breeding programs to select animals according to their robustness presents several challenges and levels of complexity. One of the most relevant milestones is the identification of selection criteria that combine functional traits with those of immunocompetence. These complex traits are driven by several physiological and behavioral mechanisms that in turn are determined by genetic and environmental factors. Regarding the genetic determinism of immunocompetence, several studies in pigs acknowledged medium to high heritability estimates [4,5,6,7,8,9] and reported genomic regions and candidate genes associated with phenotypic variation of health-related traits [9,10,11,12,13,14, Estimates of heritability and microbiability exposed the joint contribution of both the host genome and the gut microbial ecosystem to the phenotypic variance of immunity parameters, and revealed that ignoring microbiota effects on phenotypes could generate an upward bias in the estimation of genetic parameters. Results from the MWAS suggested a polymicrobial nature of the immunocompetence in pigs and highlighted associations between the compositions of pig gut microbiota and 15 of the analyzed traits. Overall, our findings establish several links between the gut microbiota and the immune system in pigs, underscoring the importance of considering both sources of information, host-genome and microbial level, for the genetic evaluation and the modulation of immunocompetence in pigs.Conclusions
Availability of data and materials
The raw sequencing data employed in this article has been submitted to the NCBI’s sequence read archive (https://www.ncbi.nlm.nih.gov/sra); BioProject: PRJNA608629.
Abbreviations
- CRP:
-
C-reactive protein in serum
- EO:
-
Eosinophils count
- γδ T-cells:
-
γδ T-lymphocyte subpopulation
- GRANU_PHAGO_FITC:
-
Granulocytes phagocytosis
- GRANU_PHAGO_%:
-
Granulocytes phagocytosis
- HP:
-
Haptoglobin in serum
- IgA:
-
IgA in plasma
- IgAsal:
-
IgA in saliva
- IgG:
-
IgG in plasma
- IgM:
-
IgM in plasma
- LEU:
-
Leukocytes count
- LYM:
-
Lymphocytes count
- LYM_PHAGO_FITC:
-
Lymphocytes phagocytosis FITC
- LYM_PHAGO_%:
-
Lymphocytes phagocytosis
- MON_PHAGO_FITC:
-
Monocytes phagocytosis FITC
- MON_PHAGO_%:
-
Monocytes phagocytosis
- MON:
-
Monocytes count
- NO:
-
Nitric oxide in serum
- PHAGO_FITC:
-
Phagocytosis FITC
- PHAGO_%:
-
Phagocytosis (% cells)
- NEU:
-
Neutrophils count
- QIIME:
-
Quantitative insights into microbial ecology
- clr:
-
Centered log ratio transformation
- MWAS:
-
Microbial-wide association studies
- PCIT:
-
Partial Correlation coefficient with Information Theory
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Acknowledgements
The authors warmly thank all technical staff from Selección Batallé S.A, for providing the animal material and their collaboration during the sampling.
Funding
YRC is recipient of a Ramon y Cajal post-doctoral fellowship (RYC2019-027244-I) from the Spanish Ministry of Science and Innovation. MB was recipient of a Ramon y Cajal post-doctoral fellowship (RYC-2013–12573). LMZ is recipient of a Ph.D. grant from Ministry of Economy and Science, Spain associated with ‘Centro de Excelencia Severo Ochoa 2016–2019’ award SEV-2015-0533 to CRAG. Part of the research presented in this publication was funded by Grants AGL2016-75432-R, AGL2017-88849-R awarded by the Spanish Ministry of Economy and Competitiveness. The authors belong to Consolidated Research Group TERRA (AGAUR, 2017 SGR 1719).
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YRC, RQ and MB designed the study. MB carried out DNA extraction. MB, RQ, TD and YRC performed the sampling. YRC, LMZ, AR and PA analyzed the data. YRC, LMZ, DP, AR, PA, RQ and MB interpreted the results and wrote the manuscript. All authors read and approved the final manuscript.
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Animal care and experimental procedures were carried out following national and institutional guidelines for the Good Experimental Practices and were approved by the IRTA Ethical Committee. Consent to participate is not applicable in this study.
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Supplementary Information
Additional file 1.
Figure 1. Iris-plot representing the 20 most abundant genera. Each bar represents a sample, and bar colors represented the genera relative abundance.
Additional file 2.
Table 1. Posterior estimates of h2 and m2 for the 21 health-related traits.
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Ramayo-Caldas, Y., Zingaretti, L.M., Pérez-Pascual, D. et al. Leveraging host-genetics and gut microbiota to determine immunocompetence in pigs. anim microbiome 3, 74 (2021). https://doi.org/10.1186/s42523-021-00138-9
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DOI: https://doi.org/10.1186/s42523-021-00138-9