Multi-omics integration and immune profiling identify possible causal networks leading to uterine microbiome dysbiosis in dairy cows that develop metritis
Abstract Background Cows that develop metritis experience dysbiosis of their uterine microbiome, where opportunistic pathogens overtake uterine commensals. An effective immune response is critical for maintaining uterine health. Nonetheless, periparturient cows experience immune dysregulation, which...
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BMC
2025-01-01
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| Series: | Animal Microbiome |
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| Online Access: | https://doi.org/10.1186/s42523-024-00366-9 |
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| author | S. Casaro J. G. Prim T. D. Gonzalez F. Cunha A. C. M. Silva H. Yu R. S. Bisinotto R. C. Chebel J. E. P. Santos C. D. Nelson S. J. Jeon R. C. Bicalho J. P. Driver Klibs N. Galvão |
| author_facet | S. Casaro J. G. Prim T. D. Gonzalez F. Cunha A. C. M. Silva H. Yu R. S. Bisinotto R. C. Chebel J. E. P. Santos C. D. Nelson S. J. Jeon R. C. Bicalho J. P. Driver Klibs N. Galvão |
| author_sort | S. Casaro |
| collection | DOAJ |
| description | Abstract Background Cows that develop metritis experience dysbiosis of their uterine microbiome, where opportunistic pathogens overtake uterine commensals. An effective immune response is critical for maintaining uterine health. Nonetheless, periparturient cows experience immune dysregulation, which seems to be intensified by prepartum over-condition. Herein, Bayesian networks were applied to investigate the directional correlations between prepartum body weight (BW), BW loss, pre- and postpartum systemic immune profiling and plasma metabolome, and postpartum uterine metabolome and microbiome. Results The Bayesian network analysis showed a positive directional correlation between prepartum BW, prepartum BW loss, and plasma fatty acids at parturition, suggesting that heavier cows were in lower energy balance than lighter cows. There was a positive directional correlation between prepartum BW, prepartum systemic leukocyte death, immune activation, systemic inflammation, and metabolomic changes associated with oxidative stress prepartum and at parturition. Immune activation and systemic inflammation were characterized by increased proportion of circulating polymorphonuclear cells (PMN) prepartum, B-cell activation at parturition, interleukin-8 prepartum and at parturition, and interleukin-1β at parturition. These immune changes together with plasma fatty acids at parturition had a positive directional correlation with PMN extravasation postpartum, which had a positive directional correlation with uterine metabolites associated with tissue damage. These results suggest that excessive PMN migration to the uterus leads to excessive endometrial damage. The aforementioned changes had a positive directional correlation with Fusobacterium, Porphyromonas, and Bacteroides in cows that developed metritis, suggesting that excessive tissue damage may disrupt physical barriers or increase substrate availability for bacterial growth. Conclusions This work provides robust mechanistic hypotheses for how prepartum BW may impact peripartum immune and metabolic profiles, which may lead to uterine opportunistic pathogens overgrowth and metritis development. |
| format | Article |
| id | doaj-art-d62e0c5506e54dda91257e76467fe6a3 |
| institution | Kabale University |
| issn | 2524-4671 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Animal Microbiome |
| spelling | doaj-art-d62e0c5506e54dda91257e76467fe6a32025-01-12T12:41:16ZengBMCAnimal Microbiome2524-46712025-01-017111110.1186/s42523-024-00366-9Multi-omics integration and immune profiling identify possible causal networks leading to uterine microbiome dysbiosis in dairy cows that develop metritisS. Casaro0J. G. Prim1T. D. Gonzalez2F. Cunha3A. C. M. Silva4H. Yu5R. S. Bisinotto6R. C. Chebel7J. E. P. Santos8C. D. Nelson9S. J. Jeon10R. C. Bicalho11J. P. Driver12Klibs N. Galvão13Department of Large Animal Clinical Sciences, University of FloridaDepartment of Clinical Sciences, Auburn UniversityDepartment of Large Animal Clinical Sciences, University of FloridaDepartment of Large Animal Clinical Sciences, University of FloridaDepartment of Animal Sciences, University of FloridaDepartment of Animal Sciences, University of FloridaDepartment of Large Animal Clinical Sciences, University of FloridaDepartment of Large Animal Clinical Sciences, University of FloridaDepartment of Animal Sciences, University of FloridaDepartment of Animal Sciences, University of FloridaDepartment of Veterinary Biomedical Sciences, Long Island UniversityFERA Diagnostics and BiologicalsDivision of Animals Sciences, University of MissouriDepartment of Large Animal Clinical Sciences, University of FloridaAbstract Background Cows that develop metritis experience dysbiosis of their uterine microbiome, where opportunistic pathogens overtake uterine commensals. An effective immune response is critical for maintaining uterine health. Nonetheless, periparturient cows experience immune dysregulation, which seems to be intensified by prepartum over-condition. Herein, Bayesian networks were applied to investigate the directional correlations between prepartum body weight (BW), BW loss, pre- and postpartum systemic immune profiling and plasma metabolome, and postpartum uterine metabolome and microbiome. Results The Bayesian network analysis showed a positive directional correlation between prepartum BW, prepartum BW loss, and plasma fatty acids at parturition, suggesting that heavier cows were in lower energy balance than lighter cows. There was a positive directional correlation between prepartum BW, prepartum systemic leukocyte death, immune activation, systemic inflammation, and metabolomic changes associated with oxidative stress prepartum and at parturition. Immune activation and systemic inflammation were characterized by increased proportion of circulating polymorphonuclear cells (PMN) prepartum, B-cell activation at parturition, interleukin-8 prepartum and at parturition, and interleukin-1β at parturition. These immune changes together with plasma fatty acids at parturition had a positive directional correlation with PMN extravasation postpartum, which had a positive directional correlation with uterine metabolites associated with tissue damage. These results suggest that excessive PMN migration to the uterus leads to excessive endometrial damage. The aforementioned changes had a positive directional correlation with Fusobacterium, Porphyromonas, and Bacteroides in cows that developed metritis, suggesting that excessive tissue damage may disrupt physical barriers or increase substrate availability for bacterial growth. Conclusions This work provides robust mechanistic hypotheses for how prepartum BW may impact peripartum immune and metabolic profiles, which may lead to uterine opportunistic pathogens overgrowth and metritis development.https://doi.org/10.1186/s42523-024-00366-9MicrobiomeMetabolomeImmune dysregulationMulti-omicsCausal networks |
| spellingShingle | S. Casaro J. G. Prim T. D. Gonzalez F. Cunha A. C. M. Silva H. Yu R. S. Bisinotto R. C. Chebel J. E. P. Santos C. D. Nelson S. J. Jeon R. C. Bicalho J. P. Driver Klibs N. Galvão Multi-omics integration and immune profiling identify possible causal networks leading to uterine microbiome dysbiosis in dairy cows that develop metritis Animal Microbiome Microbiome Metabolome Immune dysregulation Multi-omics Causal networks |
| title | Multi-omics integration and immune profiling identify possible causal networks leading to uterine microbiome dysbiosis in dairy cows that develop metritis |
| title_full | Multi-omics integration and immune profiling identify possible causal networks leading to uterine microbiome dysbiosis in dairy cows that develop metritis |
| title_fullStr | Multi-omics integration and immune profiling identify possible causal networks leading to uterine microbiome dysbiosis in dairy cows that develop metritis |
| title_full_unstemmed | Multi-omics integration and immune profiling identify possible causal networks leading to uterine microbiome dysbiosis in dairy cows that develop metritis |
| title_short | Multi-omics integration and immune profiling identify possible causal networks leading to uterine microbiome dysbiosis in dairy cows that develop metritis |
| title_sort | multi omics integration and immune profiling identify possible causal networks leading to uterine microbiome dysbiosis in dairy cows that develop metritis |
| topic | Microbiome Metabolome Immune dysregulation Multi-omics Causal networks |
| url | https://doi.org/10.1186/s42523-024-00366-9 |
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