Microbiota-metabolite axis in endometriosis: Pathogenic mechanisms and clinical implications

Abstract

Growing evidence highlights the gut, reproductive tract, and endometrial microbiota as important functional contributors in the pathogenesis of endometriosis (EM). Studies have revealed a characteristic microbial imbalance in patients with EM, marked by a reduced abundance of beneficial bacteria and an enrichment of opportunistic pathogens. These microbial communities are thought to influence disease progression primarily through metabolic activity, as demonstrated by metabolomic studies showing their capacity to modulate host immune and endocrine responses. This imbalance may contribute to several key metabolic disturbances, including decreased levels of short-chain fatty acids, particularly butyrate; a shift in tryptophan metabolism toward the kynurenine pathway; elevated β-glucuronidase activity; increased lipopolysaccharide production; and altered secondary bile acid profiles. Functionally, these metabolic alterations are thought to contribute to EM by disrupting immune homeostasis, enhancing estrogen signaling, and driving systemic inflammation, thereby creating a permissive microenvironment for ectopic lesion growth and invasion. Targeted interventions, such as probiotics, high-fiber dietary strategies, fecal microbiota transplantation, and selective modulation of microbial or host metabolic enzymes, are emerging as promising non-hormonal therapeutic approaches. Nonetheless, further studies incorporating longitudinal cohort designs and integrative multi-omics approaches are essential to establish causality and facilitate the development of precise diagnostic and personalized treatment strategies.

Keywords

endometriosis / microbiota / metabolite

References

[1] Vercellini P, Viganò P, Somigliana E, et al. Endometriosis: Pathogenesis and treatment[J]. Nat Rev Endocrinol, 2014, 10(5): 261-275. doi: 10.1038/nrendo.2013.255

[2] Sonavane SK, Kantawala KP, Menias CO. Beyond the boundaries-endometriosis: Typical and atypical locations[J]. Curr Probl Diagn Radiol, 2011, 40(6): 219-232. doi: 10.1067/j.cpradiol.2011.01.003

[3] Horne AW, Missmer SA. Pathophysiology, diagnosis, and management of endometriosis[J]. BMJ, 2022, 379: e070750. doi: 10.1136/bmj-2022-070750

[4] Ahn SH, Monsanto SP, Miller C, et al. Pathophysiology and immune dysfunction in endometriosis[J]. Biomed Res Int, 2015, 2015: 795976. doi: 10.1155/2015/795976

[5] Halme J, Hammond MG, Hulka JF, et al. Retrograde menstruation in healthy women and in patients with endometriosis[J]. Obstet Gynecol, 1984, 64(2): 151-154. https://pubmed.ncbi.nlm.nih.gov/6234483/

[6] Vallvé-Juanico J, Houshdaran S, Giudice LC. The endometrial immune environment of women with endometriosis[J]. Hum Reprod Update, 2019, 25(5): 565-592. doi: 10.1093/humupd/dmz018

[7] Symons LK, Miller JE, Kay VR, et al. The immunopathophysiology of endometriosis[J]. Trends Mol Med, 2018, 24(9): 748-762. doi: 10.1016/j.molmed.2018.07.004

[8] Polak G, Banaszewska B, Filip M, et al. Environmental factors and endometriosis[J]. Int J Environ Res Public Health, 2021, 18(21): 11025. doi: 10.3390/ijerph182111025

[9] Jiang I, Yong PJ, Allaire C, et al. Intricate connections between the microbiota and endometriosis[J]. Int J Mol Sci, 2021, 22(11): 5644. doi: 10.3390/ijms22115644

[10] Dang C, Chen Z, Chai Y, et al. Assessing the relationship between gut microbiota and endometriosis: A bidirectional two-sample Mendelian randomization analysis[J]. BMC Womens Health, 2024, 24(1): 123. doi: 10.1186/s12905-024-02945-z

[11] Ji X, Yang Q, Zhu X, et al. Association between gut microbiota and endometriosis: A two-sample Mendelian randomization study[J]. Front Microbiol, 2023, 14: 1188458. doi: 10.3389/fmicb.2023.1188458

[12] Tang Y, Yang J, Hang F, et al. Unraveling the relationship between gut microbiota and site-specific endometriosis: A Mendelian randomization analysis[J]. Front Microbiol, 2024, 15: 1363080. doi: 10.3389/fmicb.2024.1363080

[13] Hold GL, Smith M, Grange C, et al. Role of the gut microbiota in inflammatory bowel disease pathogenesis: What have we learnt in the past 10 years?[J]. World J Gastroenterol, 2014, 20(5): 1192-1210. doi: 10.3748/wjg.v20.i5.1192

[14] Arvonen M, Berntson L, Pokka T, et al. Gut microbiota-host interactions and juvenile idiopathic arthritis[J]. Pediatr Rheumatol Online J, 2016, 14(1): 44. doi: 10.1186/s12969-016-0104-6

[15] Wu N, Yang X, Zhang R, et al. Dysbiosis signature of fecal microbiota in colorectal cancer patients[J]. Microb Ecol, 2013, 66(2): 462-470. doi: 10.1007/s00248-013-0245-9

[16] Laschke MW, Menger MD. The gut microbiota: A puppet master in the pathogenesis of endometriosis?[J]. Am J Obstet Gynecol, 2016, 215(1): 68. e1-68.e4. doi: 10.1016/j.ajog.2016.02.036

[17] Flores R, Shi J, Fuhrman B, et al. Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: A cross-sectional study[J]. J Transl Med, 2012, 10(1): 253. doi: 10.1186/1479-5876-10-253

[18] Rižner TL. Estrogen metabolism and action in endometriosis[J]. Mol Cell Endocrinol, 2009, 307(1-2): 8-18. doi: 10.1016/j.mce.2009.03.022

[19] Wei W, Zhang X, Tang H, et al. Microbiota composition and distribution along the female reproductive tract of women with endometriosis[J]. Ann Clin Microbiol Antimicrob, 2020, 19(1): 15. doi: 10.1186/s12941-020-00356-0

[20] Gholiof M, Adamson-De Luca E, Wessels JM. The female reproductive tract microbiotas, inflammation, and gynecological conditions[J]. Front Reprod Health, 2022, 4: 963752. doi: 10.3389/frph.2022.963752

[21] Chen C, Song X, Wei W, et al. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases[J]. Nat Commun, 2017, 8(1): 875. doi: 10.1038/s41467-017-00901-0

[22] Yuan M, Li D, Zhang Z, et al. Endometriosis induces gut microbiota alterations in mice[J]. Hum Reprod, 2018, 33(4): 607-616. doi: 10.1093/humrep/dex372

[23] Svensson A, Brunkwall L, Roth B, et al. Associations between endometriosis and gut microbiota[J]. Reprod Sci, 2021, 28(8): 2367-2377. doi: 10.1007/s43032-021-00506-5

[24] Hantschel J, Weis S, Schäfer KH, et al. Effect of endometriosis on the fecal bacteriota composition of mice during the acute phase of lesion formation[J]. PLoS One, 2019, 14(12): e0226835. doi: 10.1371/journal.pone.0226835

[25] Ata B, Yildiz S, Turkgeldi E, et al. The endobiota study: Comparison of vaginal, cervical and gut microbiota between women with Stage 3/4 endometriosis and healthy controls[J]. Sci Rep, 2019, 9(1): 2204. doi: 10.1038/s41598-019-39700-6

[26] Bailey MT, Coe CL. Endometriosis is associated with an altered profile of intestinal microflora in female rhesus monkeys[J]. Hum Reprod, 2002, 17(7): 1704-1708. doi: 10.1093/humrep/17.7.1704

[27] Magne F, Gotteland M, Gauthier L, et al. The firmicutes/Bacteroidetes ratio: A relevant marker of gut dysbiosis in obese patients?[J]. Nutrients, 2020, 12(5): 1474. doi: 10.3390/nu12051474

[28] Chadchan SB, Cheng M, Parnell LA, et al. Antibiotic therapy with metronidazole reduces endometriosis disease progression in mice: A potential role for gut microbiota[J]. Hum Reprod, 2019, 34(6): 1106-1116. doi: 10.1093/humrep/dez041

[29] Castaño-Rodríguez N, Underwood AP, Merif J, et al. Gut microbiome analysis identifies potential etiological factors in acute gastroenteritis[J]. Infect Immun, 2018, 86(7): e00060-18. doi: 10.1128/iai.00060-18

[30] Mendiola J, Sánchez-Ferrer ML, Jiménez-Velázquez R, et al. Endometriomas and deep infiltrating endometriosis in adulthood are strongly associated with anogenital distance, a biomarker for prenatal hormonal environment[J]. Hum Reprod, 2016, 31(10): 2377-2383. doi: 10.1093/humrep/dew163

[31] Salliss ME, Farland LV, Mahnert ND, et al. The role of gut and genital microbiota and the estrobolome in endometriosis, infertility and chronic pelvic pain[J]. Hum Reprod Update, 2022, 28(1): 92-131. doi: 10.1093/humupd/dmab035

[32] Akiyama K, Nishioka K, Khan KN, et al. Molecular detection of microbial colonization in cervical mucus of women with and without endometriosis[J]. Am J Reprod Immunol, 2019, 82(2): e13147. doi: 10.1111/aji.13147

[33] Fredricks DN, Fiedler TL, Marrazzo JM. Molecular identification of bacteria associated with bacterial vaginosis[J]. N Engl J Med, 2005, 353(18): 1899-1911. doi: 10.1056/NEJMoa043802

[34] Khan KN, Fujishita A, Kitajima M, et al. Intra-uterine microbial colonization and occurrence of endometritis in women with endometriosis[J]. Hum Reprod, 2014, 29(11): 2446-2456. doi: 10.1093/humrep/deu222

[35] Muhleisen AL, Herbst-Kralovetz MM. Menopause and the vaginal microbiome[J]. Maturitas, 2016, 91: 42-50. doi: 10.1016/j.maturitas.2016.05.015

[36] Nejman D, Livyatan I, Fuks G, et al. The human tumor microbiome is composed of tumor type-specific intracellular bacteria[J]. Science, 2020, 368(6494): 973-980. doi: 10.1126/science.aay9189

[37] Brennan CA, Garrett WS. Fusobacterium nucleatum-symbiont, opportunist and oncobacterium[J]. Nat Rev Microbiol, 2019, 17(3): 156-166. doi: 10.1038/s41579-018-0129-6

[38] Muraoka A, Suzuki M, Hamaguchi T, et al. Fusobacterium infection facilitates the development of endometriosis through the phenotypic transition of endometrial fibroblasts[J]. Sci Transl Med, 2023, 15(700): eadd1531. doi: 10.1126/scitranslmed.add1531

[39] Guo W, Xu Z, Hu S, et al. Exploring microbial signatures in endometrial tissues with endometriosis[J]. Int Immunopharmacol, 2025, 148: 114072. doi: 10.1016/j.intimp.2025.114072

[40] Agarwal K, Robinson LS, Aggarwal S, et al. Glycan cross-feeding supports mutualism between Fusobacterium and the vaginal microbiota[J]. PLoS Biol, 2020, 18(8): e3000788. doi: 10.1371/journal.pbio.3000788

[41] Wu X, Wu M, Li H, et al. Intraperitoneal translocation of gut microbiota induces NETosis and promotes endometriosis[J]. Gut, 2026, 75(6): 1110-1122. doi: 10.1136/gutjnl-2025-336185

[42] Graciano-España MC, Barnhart K, Gonzalez-Monfort M, et al. Fusobacterium nucleatum is not significantly present in eutopic endometrium from patients with minimal-mild and moderate-severe endometriosis[J]. Fertil Steril, 2025, 124(5 Pt 2): 1071-1081. doi: 10.1016/j.fertnstert.2025.06.035

[43] Talwar C, Davuluri GVN, Kamal AHM, et al. Identification of distinct stool metabolites in women with endometriosis for non-invasive diagnosis and potential for microbiota-based therapies[J]. Med, 2025, 6(2): 100517. doi: 10.1016/j.medj.2024.09.006

[44] Syggelou A, Iacovidou N, Atzori L, et al. Metabolomics in the developing human being[J]. Pediatr Clin North Am, 2012, 59(5): 1039-1058. doi: 10.1016/j.pcl.2012.07.002

[45] Dalile B, Van Oudenhove L, Vervliet B, et al. The role of short-chain fatty acids in microbiota-gut-brain communication[J]. Nat Rev Gastroenterol Hepatol, 2019, 16(8): 461-478. doi: 10.1038/s41575-019-0157-3

[46] Agus A, Planchais J, Sokol H. Gut microbiota regulation of tryptophan metabolism in health and disease[J]. Cell Host Microbe, 2018, 23(6): 716-724. doi: 10.1016/j.chom.2018.05.003

[47] Ridlon JM, Kang DJ, Hylemon PB. Bile salt biotransformations by human intestinal bacteria[J]. J Lipid Res, 2006, 47(2): 241-259. doi: 10.1194/jlr.R500013-JLR200

[48] Zhang X, Tian X, Wang Y, et al. Application of lipopolysaccharide in establishing inflammatory models[J]. Int J Biol Macromol, 2024, 279: 135371. doi: 10.1016/j.ijbiomac.2024.135371

[49] Baker JM, Al-Nakkash L, Herbst-Kralovetz MM. Estrogen-gut microbiome axis: Physiological and clinical implications[J]. Maturitas, 2017, 103: 45-53. doi: 10.1016/j.maturitas.2017.06.025

[50] Basson A, Trotter A, Rodriguez-Palacios A, et al. Mucosal interactions between genetics, diet, and microbiome in inflammatory bowel disease[J]. Front Immunol, 2016, 7: 290. doi: 10.3389/fimmu.2016.00290

[51] Mukherjee A, Lordan C, Ross RP, et al. Gut microbes from the phylogenetically diverse genus Eubacterium and their various contributions to gut health[J]. Gut Microbes, 2020, 12(1): 1802866. doi: 10.1080/19490976.2020.1802866

[52] Jin M, Kalainy S, Baskota N, et al. Faecal microbiota from patients with cirrhosis has a low capacity to ferment non-digestible carbohydrates into short-chain fatty acids[J]. Liver Int, 2019, 39(8): 1437-1447. doi: 10.1111/liv.14106

[53] Tremaroli V, Bäckhed F. Functional interactions between the gut microbiota and host metabolism[J]. Nature, 2012, 489(7415): 242-249. doi: 10.1038/nature11552

[54] Mao J, Wang D, Long J, et al. Gut microbiome is associated with the clinical response to anti-PD-1 based immunotherapy in hepatobiliary cancers[J]. J Immunother Cancer, 2021, 9(12): e003334. doi: 10.1136/jitc-2021-003334

[55] Wozniak H, Beckmann TS, Fröhlich L, et al. The central and biodynamic role of gut microbiota in critically ill patients[J]. Crit Care, 2022, 26(1): 250. doi: 10.1186/s13054-022-04127-5

[56] Furusawa Y, Obata Y, Fukuda S, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells[J]. Nature, 2013, 504(7480): 446-450. doi: 10.1038/nature12721

[57] Singh N, Gurav A, Sivaprakasam S, et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis[J]. Immunity, 2014, 40(1): 128-139. doi: 10.1016/j.immuni.2013.12.007

[58] Guo J, Wang Y, Jiang P, et al. Sodium butyrate alleviates lipopolysaccharide-induced endometritis in mice through inhibiting inflammatory response[J]. Microb Pathog, 2019, 137: 103792. doi: 10.1016/j.micpath.2019.103792

[59] Cui H, Wang N, Li H, et al. The dynamic shifts of IL-10-producing Th17 and IL-17-producing Treg in health and disease: A crosstalk between ancient "Yin-Yang" theory and modern immunology[J]. Cell Commun Signal, 2024, 22(1): 99. doi: 10.1186/s12964-024-01505-0

[60] Petersen C, Round JL. Defining dysbiosis and its influence on host immunity and disease[J]. Cell Microbiol, 2014, 16(7): 1024-1033. doi: 10.1111/cmi.12308

[61] Vinolo MAR, Rodrigues HG, Nachbar RT, et al. Regulation of inflammation by short chain fatty acids[J]. Nutrients, 2011, 3(10): 858-876. doi: 10.3390/nu3100858

[62] Lucas JL, Mirshahpanah P, Haas-Stapleton E, et al. Induction of Foxp3⁺ regulatory T cells with histone deacetylase inhibitors[J]. Cell Immunol, 2009, 257(1-2): 97-104. doi: 10.1016/j.cellimm.2009.03.004

[63] Tanaka Y, Mori T, Ito F, et al. Exacerbation of endometriosis due to regulatory T-cell dysfunction[J]. J Clin Endocrinol Metab, 2017, 102(9): 3206-3217. doi: 10.1210/jc.2017-00052

[64] Chadchan SB, Popli P, Ambati CR, et al. Gut microbiota-derived short-chain fatty acids protect against the progression of endometriosis[J]. Life Sci Alliance, 2021, 4(12): e202101224. doi: 10.26508/lsa.202101224

[65] Lu N, Li M, Lei H, et al. Butyric acid regulates progesterone and estradiol secretion via cAMP signaling pathway in porcine granulosa cells[J]. J Steroid Biochem Mol Biol, 2017, 172: 89-97. doi: 10.1016/j.jsbmb.2017.06.004

[66] Huang L, Liu B, Liu Z, et al. Gut microbiota exceeds cervical microbiota for early diagnosis of endometriosis[J]. Front Cell Infect Microbiol, 2021, 11: 788836. doi: 10.3389/fcimb.2021.788836

[67] Zelante T, Iannitti RG, Cunha C, et al. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22[J]. Immunity, 2013, 39(2): 372-385. doi: 10.1016/j.immuni.2013.08.003

[68] Wlodarska M, Luo C, Kolde R, et al. Indoleacrylic acid produced by commensal Peptostreptococcus species suppresses inflammation[J]. Cell Host Microbe, 2017, 22(1): 25-37.e6. doi: 10.1016/j.chom.2017.06.007

[69] Hubbard TD, Murray IA, Perdew GH. Indole and tryptophan metabolism: Endogenous and dietary routes to Ah receptor activation[J]. Drug Metab Dispos, 2015, 43(10): 1522-1535. doi: 10.1124/dmd.115.064246

[70] Williams BB, Van Benschoten AH, Cimermancic P, et al. Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine[J]. Cell Host Microbe, 2014, 16(4): 495-503. doi: 10.1016/j.chom.2014.09.001

[71] Lamas B, Richard ML, Leducq V, et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands[J]. Nat Med, 2016, 22(6): 598-605. doi: 10.1038/nm.4102

[72] Galligan JJ. Beneficial actions of microbiota-derived tryptophan metabolites[J]. Neurogastroenterol Motil, 2018, 30(2): e13283. doi: 10.1111/nmo.13283

[73] Lee JH, Wood TK, Lee J. Roles of indole as an interspecies and interkingdom signaling molecule[J]. Trends Microbiol, 2015, 23(11): 707-718. doi: 10.1016/j.tim.2015.08.001

[74] Mor A, Tankiewicz-Kwedlo A, Ciwun M, et al. Kynurenines as a novel target for the treatment of inflammatory disorders[J]. Cells, 2024, 13(15): 1259. doi: 10.3390/cells13151259

[75] Bergqvist A, Bruse C, Carlberg M, et al. Interleukin 1β interleukin-6, and tumor necrosis factor-α in endometriotic tissue and in endometrium[J]. Fertil Steril, 2001, 75(3): 489-495. doi: 10.1016/S0015-0282(00)01752-0

[76] Chadchan SB, Naik SK, Popli P, et al. Gut microbiota and microbiota-derived metabolites promotes endometriosis[J]. Cell Death Discov, 2023, 9(1): 28. doi: 10.1038/s41420-023-01309-0

[77] Mariuzzi L, Domenis R, Orsaria M, et al. Functional expression of aryl hydrocarbon receptor on mast cells populating human endometriotic tissues[J]. Lab Invest, 2016, 96(9): 959-971. doi: 10.1038/labinvest.2016.74

[78] Esser C, Rannug A. The aryl hydrocarbon receptor in barrier organ physiology, immunology, and toxicology[J]. Pharmacol Rev, 2015, 67(2): 259-279. doi: 10.1124/pr.114.009001

[79] Monnin N, Fattet AJ, Koscinski I. Endometriosis: Update of pathophysiology, (Epi) genetic and environmental involvement[J]. Biomedicines, 2023, 11(3): 978. doi: 10.3390/biomedicines11030978

[80] Lu J, Ling X, Liu L, et al. Emerging hallmarks of endometriosis metabolism: A promising target for the treatment of endometriosis[J]. Biochim Biophys Acta Mol Cell Res, 2023, 1870(1): 119381. doi: 10.1016/j.bbamcr.2022.119381

[81] Sinha SR, Haileselassie Y, Nguyen LP, et al. Dysbiosis-induced secondary bile acid deficiency promotes intestinal inflammation[J]. Cell Host Microbe, 2020, 27(4): 659-670.e5. doi: 10.1016/j.chom.2020.01.021

[82] Zhao W, Wang J, Li X, et al. Deoxycholic acid inhibits Staphylococcus aureus-induced endometritis through regulating TGR5/PKA/NF-κB signaling pathway[J]. Int Immunopharmacol, 2023, 118: 110004. doi: 10.1016/j.intimp.2023.110004

[83] Yoneno K, Hisamatsu T, Shimamura K, et al. TGR5 signalling inhibits the production of pro-inflammatory cytokines by in vitro differentiated inflammatory and intestinal macrophages in Crohn's disease[J]. Immunology, 2013, 139(1): 19-29. doi: 10.1111/imm.12045

[84] Lyu D, Tang N, Wang J, et al. TGR5 agonist INT-777 mitigates inflammatory response in human endometriotic stromal cells: A therapeutic implication for endometriosis[J]. Int Immunopharmacol, 2019, 71: 93-99. doi: 10.1016/j.intimp.2019.02.044

[85] Sakamoto Y, Harada T, Horie S, et al. Tumor necrosis factor-α-induced interleukin-8 (IL-8) expression in endometriotic stromal cells, probably through nuclear factor-κB activation: Gonadotropin-releasing hormone agonist treatment reduced IL-8 expression[J]. J Clin Endocrinol Metab, 2003, 88(2): 730-735. doi: 10.1210/jc.2002-020666

[86] Azuma Y, Taniguchi F, Nakamura K, et al. Lipopolysaccharide promotes the development of murine endometriosis-like lesions via the nuclear factor-kappa B pathway[J]. Am J Reprod Immunol, 2017, 77(4): e12631. doi: 10.1111/aji.12631

[87] Khan KN, Fujishita A, Hiraki K, et al. Bacterial contamination hypothesis: A new concept in endometriosis[J]. Reprod Med Biol, 2018, 17(2): 125-133. doi: 10.1002/rmb2.12083

[88] Li Z, Yin Z, Chen W, et al. Impact of gut and reproductive tract microbiota on estrogen metabolism in endometriosis[J]. Am J Reprod Immunol, 2025, 93(6): e70109. doi: 10.1111/aji.70109

[89] Chen P, Wang K, Zhuang M, et al. An insight into gut microbiota and metabolites in the mice with adenomyosis[J]. Front Cell Infect Microbiol, 2023, 13: 1075387. doi: 10.3389/fcimb.2023.1075387

[90] Ni Z, Sun S, Bi Y, et al. Correlation of fecal metabolomics and gut microbiota in mice with endometriosis[J]. Am J Reprod Immunol, 2020, 84(6): e13307. doi: 10.1111/aji.13307

[91] Parasar P, Ozcan P, Terry KL. Endometriosis: Epidemiology, diagnosis and clinical management[J]. Curr Obstet Gynecol Rep, 2017, 6(1): 34-41. doi: 10.1007/s13669-017-0187-1

[92] Su Q, Liu Q, Lau RI, et al. Faecal microbiome-based machine learning for multi-class disease diagnosis[J]. Nat Commun, 2022, 13(1): 6818. doi: 10.1038/s41467-022-34405-3

[93] Ghosh A, Jaaback K, Boulton A, et al. Fusobacterium nucleatum: An overview of evidence, demi-decadal trends, and its role in adverse pregnancy outcomes and various gynecological diseases, including cancers[J]. Cells, 2024, 13(8): 717. doi: 10.3390/cells13080717

[94] Zhang X, Zhu X, Cao Y, et al. Fecal Fusobacterium nucleatum for the diagnosis of colorectal tumor: A systematic review and meta-analysis[J]. Cancer Med, 2019, 8(2): 480-491. doi: 10.1002/cam4.1850

[95] Chen W, Zhang X, Zhang M, et al. Salivary Fusobacterium nucleatum serves as a potential diagnostic biomarker for gastric cancer[J]. World J Gastroenterol, 2022, 28(30): 4120-4132. doi: 10.3748/wjg.v28.i30.4120

[96] Iavarone I, Greco PF, La Verde M, et al. Correlations between gut microbial composition, pathophysiological and surgical aspects in endometriosis: A review of the literature[J]. Medicina (Kaunas), 2023, 59(2): 347. doi: 10.3390/medicina59020347

[97] Ortiz CN, Torres-Reverón A, Appleyard CB. Metabolomics in endometriosis: Challenges and perspectives for future studies[J]. Reprod Fertil, 2021, 2(2): R35-R50. doi: 10.1530/RAF-20-0047

[98] Dai C, Cao Y, Xu Y, et al. Serum metabolic fingerprinting for diagnosis and therapeutic applications of ovarian endometriosis[J]. iScience, 2026, 29(3): 114887. doi: 10.1016/j.isci.2026.114887

[99] Ariyoshi T, Hagihara M, Takahashi M, et al. Effect of Clostridium butyricum on gastrointestinal infections[J]. Biomedicines, 2022, 10(2): 483. doi: 10.3390/biomedicines10020483

[100] Moens F, Van den Abbeele P, Basit AW, et al. A four-strain probiotic exerts positive immunomodulatory effects by enhancing colonic butyrate production in vitro[J]. Int J Pharm, 2019, 555: 1-10. doi: 10.1016/j.ijpharm.2018.11.020

[101] Itoh H, Sashihara T, Hosono A, et al. Lactobacillus gasseri OLL2809 inhibits development of ectopic endometrial cell in peritoneal cavity via activation of NK cells in a murine endometriosis model[J]. Cytotechnology, 2011, 63(2): 205-210. doi: 10.1007/s10616-011-9343-z

[102] Li Y, Wang K, Ding J, et al. Influence of the gut microbiota on endometriosis: Potential role of chenodeoxycholic acid and its derivatives[J]. Front Pharmacol, 2022, 13: 954684. doi: 10.3389/fphar.2022.954684

[103] Guasch-Ferré M, Willett WC. The Mediterranean diet and health: A comprehensive overview[J]. J Intern Med, 2021, 290(3): 549-566. doi: 10.1111/joim.13333

[104] Shahidi F, Ambigaipalan P. Omega-3 polyunsaturated fatty acids and their health benefits[J]. Annu Rev Food Sci Technol, 2018, 9: 345-381. doi: 10.1146/annurev-food-111317-095850

[105] Parazzini F, Viganò P, Candiani M, et al. Diet and endometriosis risk: A literature review[J]. Reprod Biomed Online, 2013, 26(4): 323-336. doi: 10.1016/j.rbmo.2012.12.011

[106] Kim YS, Milner JA. Targets for indole-3-carbinol in cancer prevention[J]. J Nutr Biochem, 2005, 16(2): 65-73. doi: 10.1016/j.jnutbio.2004.10.007

[107] Quaranta G, Sanguinetti M, Masucci L. Fecal microbiota transplantation: A potential tool for treatment of human female reproductive tract diseases[J]. Front Immunol, 2019, 10: 2653. doi: 10.3389/fimmu.2019.02653

[108] Merrick B, Allen L, Masirah M Zain N, et al. Regulation, risk and safety of fecal microbiota transplant[J]. Infect Prev Pract, 2020, 2(3): 100069. doi: 10.1016/j.infpip.2020.100069

[109] Gupta S, Mullish BH, Allegretti JR. Fecal microbiota transplantation: The evolving risk landscape[J]. Am J Gastroenterol, 2021, 116(4): 647-656. doi: 10.14309/ajg.0000000000001075

[110] Al-Bakri AG, Akour AA, Al-Delaimy WK. Knowledge, attitudes, ethical and social perspectives towards fecal microbiota transplantation (FMT) among Jordanian healthcare providers[J]. BMC Med Ethics, 2021, 22(1): 19. doi: 10.1186/s12910-021-00587-6