Connecting gut microbiome composition to symptom severity and host genetics in endometriosis
- 1Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”
- 2Department of Medicine, Surgery and Health Sciences, University of Trieste
Abstract
Background: Endometriosis (EM) is a multifactorial, estrogen-dependent inflammatory disease characterized by high clinical variability. Growing evidence is highlighting the role of gut microbiome dysbiosis in EM pathophysiology; however, associations between microbiome, symptom severity, and host genetics remain poorly characterized. Extra-oral taste receptor genes (TGs), expressed in both the gastrointestinal and female reproductive systems, may represent novel mediators of gut-reproductive tract axis crosstalk.
Methods: A total of 50 women with surgically confirmed EM were deeply clinically characterized, including the evaluation of EM-symptoms and their severity. Microbiome profiles were obtained by 16S rRNA gene sequencing of rectal swabs. Genetic variants within four TGs ( TAS2R3, TAS2R4, TAS2R5, and TAS2R14 ) were assessed using SNP-array genotyping. Microbiome composition was investigated through the evaluation of alpha and beta diversity, as well as enterotype classification analyses. Associations between EM-related features, bacterial taxa and TG-SNPs were investigated using regression models.
Results: Three distinct gut microbiome community types were identified, dominated by Bacteroides , Prevotella , and Escherichia–Shigella . While microbiome composition did not differ significantly across EM stages, beta diversity was associated with dysmenorrhea (R ² = 0.13) and disease stage (R ² = 0.12). Regarding TGs, SNPs within TAS2R14 gene showed significant associations with alpha and beta diversity indices. Reduced abundance of short-chain fatty acid–producing taxa, including members of the Lachnospiraceae and Ruminococcaceae families, was associated with dysmenorrhea, whereas increased abundance of Prevotella and Mobiluncus with dysuria and infertility, respectively. Finally, an increased premenstrual pain severity was associated with a reduced relative abundance of taxa within the order Burkholderiales ( β = −2.265) and the family Sutterellaceae ( β = −1.563); high postmenstrual pain severity was associated with a lower abundance of Bifidobacteriales ( β = −4.932) and Bifidobacteriaceae ( β = −4.134).
Conclusion: This case-only study elucidated the complex relationship between gut microbiome composition, EM-related symptoms, and host genetic variation. In particular, extra-oral taste receptor genes emerged as novel risk factors to host–microbiome interactions, supporting their potential role in the microbiota-endometriosis axis and opening new perspectives on EM pathogenesis.
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BibTeX
@article{nardone2026connecting,
title = {{Connecting gut microbiome composition to symptom severity and host genetics in endometriosis}},
author = {Giuseppe Giovanni Nardone and Lara Emily Rosso and Aurora Santin and Beatrice Spedicati and Stefania Cappellani and Maria Pina Concas and Gabriella Zito and Federico Romano and Giovanni Di Lorenzo and Nunzia Zanotta and Giuseppina Campisciano and Giuseppe Ricci and Manola Comar and Giorgia Girotto},
journal = {Frontiers in Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fmicb.2026.1873766},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1873766/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Connecting gut microbiome composition to symptom severity and host genetics in endometriosis
AU - Giuseppe Giovanni Nardone
AU - Lara Emily Rosso
AU - Aurora Santin
AU - Beatrice Spedicati
AU - Stefania Cappellani
AU - Maria Pina Concas
AU - Gabriella Zito
AU - Federico Romano
AU - Giovanni Di Lorenzo
AU - Nunzia Zanotta
AU - Giuseppina Campisciano
AU - Giuseppe Ricci
AU - Manola Comar
AU - Giorgia Girotto
PY - 2026
DA - 2026/10/05
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1873766
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1873766/full
AB - Background: Endometriosis (EM) is a multifactorial, estrogen-dependent inflammatory disease characterized by high clinical variability. Growing evidence is highlighting the role of gut microbiome dysbiosis in EM pathophysiology; however, associations between microbiome, symptom severity, and host genetics remain poorly characterized. Extra-oral taste receptor genes (TGs), expressed in both the gastrointestinal and female reproductive systems, may represent novel mediators of gut-reproductive tract axis crosstalk. Methods: A total of 50 women with surgically confirmed EM were deeply clinically characterized, including the evaluation of EM-symptoms and their severity. Microbiome profiles were obtained by 16S rRNA gene sequencing of rectal swabs. Genetic variants within four TGs ( TAS2R3, TAS2R4, TAS2R5, and TAS2R14 ) were assessed using SNP-array genotyping. Microbiome composition was investigated through the evaluation of alpha and beta diversity, as well as enterotype classification analyses. Associations between EM-related features, bacterial taxa and TG-SNPs were investigated using regression models. Results: Three distinct gut microbiome community types were identified, dominated by Bacteroides , Prevotella , and Escherichia–Shigella . While microbiome composition did not differ significantly across EM stages, beta diversity was associated with dysmenorrhea (R ² = 0.13) and disease stage (R ² = 0.12). Regarding TGs, SNPs within TAS2R14 gene showed significant associations with alpha and beta diversity indices. Reduced abundance of short-chain fatty acid–producing taxa, including members of the Lachnospiraceae and Ruminococcaceae families, was associated with dysmenorrhea, whereas increased abundance of Prevotella and Mobiluncus with dysuria and infertility, respectively. Finally, an increased premenstrual pain severity was associated with a reduced relative abundance of taxa within the order Burkholderiales ( β = −2.265) and the family Sutterellaceae ( β = −1.563); high postmenstrual pain severity was associated with a lower abundance of Bifidobacteriales ( β = −4.932) and Bifidobacteriaceae ( β = −4.134). Conclusion: This case-only study elucidated the complex relationship between gut microbiome composition, EM-related symptoms, and host genetic variation. In particular, extra-oral taste receptor genes emerged as novel risk factors to host–microbiome interactions, supporting their potential role in the microbiota-endometriosis axis and opening new perspectives on EM pathogenesis.
SN - 1664-302X
ER -