Chronic Intestinal Inflammation and Microbial Dysbiosis Are Associated With Female Reproductive Outcomes in a Mouse Model of Inflammatory Bowel Disease
Background and Aims: The mechanism for increased infertility and adverse pregnancy outcomes in women with active inflammatory bowel disease is unknown. We aimed to create a murine model of chronic gut inflammation to study the pathogenesis of reproductive outcomes in inflammatory bowel disease. Meth...
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Elsevier
2025-01-01
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| Series: | Gastro Hep Advances |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772572325000573 |
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| author | Maria Martell Clare F. Quarnstrom Alexander Khoruts Vaiva Vezys Christopher Staley Eugenia Shmidt |
| author_facet | Maria Martell Clare F. Quarnstrom Alexander Khoruts Vaiva Vezys Christopher Staley Eugenia Shmidt |
| author_sort | Maria Martell |
| collection | DOAJ |
| description | Background and Aims: The mechanism for increased infertility and adverse pregnancy outcomes in women with active inflammatory bowel disease is unknown. We aimed to create a murine model of chronic gut inflammation to study the pathogenesis of reproductive outcomes in inflammatory bowel disease. Methods: Chronic intestinal inflammation was induced with dextran sodium sulfate (DSS) in specific-pathogen–free (SPF) female mice. SPF mice not treated with DSS served as controls. Daily estrous cycle monitoring was performed. Age-matched groups were cohabitated with SPF males for mating purposes. Pup weights, litter sizes, reproductive hormone serologies, peripheral and mucosal immune changes, and 16S rRNA gene taxonomic profiling of the fecal microbiome were measured and characterized. Results: DSS treatment led to weight loss, increased disease activity index scores, and reduced colon lengths. Compared to SPF controls, DSS mice spent less time in the estrus phase of the reproductive cycle (P < .05) and had decreased litter sizes and pup weights (P < .05). DSS-treated mice had lower anti-müllerian hormone and luteinizing hormone (P < .05) concentrations and higher estradiol (P < .05) concentrations. Among DSS mice, Turicibacter abundance correlated positively with the proportion of circulating neutrophils and proinflammatory cytokines and serum estradiol (Spearman ρ = 0.538–0.650, P < .001–.002). Lactobacillus and Prevotellaceae positively correlated with pup weights, litter size, estrus phase duration, luteinizing hormone, and immune cell changes from the colon and peripheral blood (ρ = 0.475–0.695, P < .01). Conclusion: Chronic bowel inflammation induces gut dysbiosis and likely contributes to adverse reproductive outcomes through endocrine imbalances. Further investigation with human studies is needed. |
| format | Article |
| id | doaj-art-e679ba155cf64e169f3bd4ce66ad5f9d |
| institution | OA Journals |
| issn | 2772-5723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Gastro Hep Advances |
| spelling | doaj-art-e679ba155cf64e169f3bd4ce66ad5f9d2025-08-20T02:37:41ZengElsevierGastro Hep Advances2772-57232025-01-014710067010.1016/j.gastha.2025.100670Chronic Intestinal Inflammation and Microbial Dysbiosis Are Associated With Female Reproductive Outcomes in a Mouse Model of Inflammatory Bowel DiseaseMaria Martell0Clare F. Quarnstrom1Alexander Khoruts2Vaiva Vezys3Christopher Staley4Eugenia Shmidt5Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, Minnesota; BioTechnology Institute, University of Minnesota, Saint Paul, MinnesotaCenter for Immunology, University of Minnesota, Minneapolis, Minnesota; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MinnesotaCenter for Immunology, University of Minnesota, Minneapolis, Minnesota; Division of Gastroenterology, Department of Medicine, University of Minnesota, Minneapolis, MinnesotaCenter for Immunology, University of Minnesota, Minneapolis, Minnesota; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MinnesotaDivision of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, Minnesota; BioTechnology Institute, University of Minnesota, Saint Paul, MinnesotaDivision of Gastroenterology, Department of Medicine, University of Minnesota, Minneapolis, Minnesota; Correspondence: Address correspondence to: Eugenia Shmidt, MD, Division of Gastroenterology, Department of Medicine, University of Minnesota, 1-213 Phillips Wangensteen Building, 516 Delaware Street S.E. MMC 36, Minneapolis, Minnesota 55455.Background and Aims: The mechanism for increased infertility and adverse pregnancy outcomes in women with active inflammatory bowel disease is unknown. We aimed to create a murine model of chronic gut inflammation to study the pathogenesis of reproductive outcomes in inflammatory bowel disease. Methods: Chronic intestinal inflammation was induced with dextran sodium sulfate (DSS) in specific-pathogen–free (SPF) female mice. SPF mice not treated with DSS served as controls. Daily estrous cycle monitoring was performed. Age-matched groups were cohabitated with SPF males for mating purposes. Pup weights, litter sizes, reproductive hormone serologies, peripheral and mucosal immune changes, and 16S rRNA gene taxonomic profiling of the fecal microbiome were measured and characterized. Results: DSS treatment led to weight loss, increased disease activity index scores, and reduced colon lengths. Compared to SPF controls, DSS mice spent less time in the estrus phase of the reproductive cycle (P < .05) and had decreased litter sizes and pup weights (P < .05). DSS-treated mice had lower anti-müllerian hormone and luteinizing hormone (P < .05) concentrations and higher estradiol (P < .05) concentrations. Among DSS mice, Turicibacter abundance correlated positively with the proportion of circulating neutrophils and proinflammatory cytokines and serum estradiol (Spearman ρ = 0.538–0.650, P < .001–.002). Lactobacillus and Prevotellaceae positively correlated with pup weights, litter size, estrus phase duration, luteinizing hormone, and immune cell changes from the colon and peripheral blood (ρ = 0.475–0.695, P < .01). Conclusion: Chronic bowel inflammation induces gut dysbiosis and likely contributes to adverse reproductive outcomes through endocrine imbalances. Further investigation with human studies is needed.http://www.sciencedirect.com/science/article/pii/S2772572325000573Inflammatory Bowel DiseaseFemale InfertilityIntestinal InflammationGut Microbiome |
| spellingShingle | Maria Martell Clare F. Quarnstrom Alexander Khoruts Vaiva Vezys Christopher Staley Eugenia Shmidt Chronic Intestinal Inflammation and Microbial Dysbiosis Are Associated With Female Reproductive Outcomes in a Mouse Model of Inflammatory Bowel Disease Gastro Hep Advances Inflammatory Bowel Disease Female Infertility Intestinal Inflammation Gut Microbiome |
| title | Chronic Intestinal Inflammation and Microbial Dysbiosis Are Associated With Female Reproductive Outcomes in a Mouse Model of Inflammatory Bowel Disease |
| title_full | Chronic Intestinal Inflammation and Microbial Dysbiosis Are Associated With Female Reproductive Outcomes in a Mouse Model of Inflammatory Bowel Disease |
| title_fullStr | Chronic Intestinal Inflammation and Microbial Dysbiosis Are Associated With Female Reproductive Outcomes in a Mouse Model of Inflammatory Bowel Disease |
| title_full_unstemmed | Chronic Intestinal Inflammation and Microbial Dysbiosis Are Associated With Female Reproductive Outcomes in a Mouse Model of Inflammatory Bowel Disease |
| title_short | Chronic Intestinal Inflammation and Microbial Dysbiosis Are Associated With Female Reproductive Outcomes in a Mouse Model of Inflammatory Bowel Disease |
| title_sort | chronic intestinal inflammation and microbial dysbiosis are associated with female reproductive outcomes in a mouse model of inflammatory bowel disease |
| topic | Inflammatory Bowel Disease Female Infertility Intestinal Inflammation Gut Microbiome |
| url | http://www.sciencedirect.com/science/article/pii/S2772572325000573 |
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