Difference of the gut microbiota of premature ovarian insufficiency in two traditional Chinese syndromes

doi:10.19852/j.cnki.jtcm.2025.01.012

Abstract

Abstract:

PURPOSE: To investigate the differences in gut microbial characteristics between two traditional Chinese syndromes of premature ovarian insufficiency (POI).

METHODS: Forty women with POI were recruited from the Department of Traditional Chinese Medicine at Shenzhen Maternity and Child Healthcare Hospital between June and December 2020. Women with POI were divided into the kidney deficiency and blood stasis syndrome (SDBS) and Qi and blood deficiency syndrome (QBDS) groups. Gut microbial community profiles were analyzed by 16S rRNA gene sequencing using an Illumina MiSeq system. A retrospective study comparing hormone levels and gut microbiota information was performed between the SDBS and QBDS groups.

RESULTS: Compared with the QBDS group, the serum levels of estradiol (E2) and anti-Müllerian hormone (AMH) were significantly decreased in the SDBS group. The quantities of Adlercreutzia, Eggerthella, Klebsiella, and Paraprevotella significantly increased in the SDBS group, whereas Lactobacillus decreased significantly. Moreover, alterations in the microbiome in the SDBS and QBDS groups were closely related to the levels of E2 and AMH. The area under the receiver operating characteristic curve for the classification of the two syndromes by the gut microbiome was 0.71.

CONCLUSIONS: There were significant differences in the dominant microbiota between the SDBS and QBDS groups, and the change in Proteobacteria in the QBDS group was more significant. The characteristics of gut microbiota help us differentiate between the SDBS and QBDS groups, which may provide a basis for the objectification of TCM syndrome types.

Key words: primary ovarian insufficiency, gastrointestinal microbiome, RNA, ribosomal, 16S, gonadal steroid hormones, traditional Chinese syndromes

WU Jiaman, NING Yan, TAN Liya, MA Fei, LIN Yanting, ZHUO Yuanyuan. Difference of the gut microbiota of premature ovarian insufficiency in two traditional Chinese syndromes[J]. Journal of Traditional Chinese Medicine, 2025, 45(1): 132-139.

Figures/Tables 5

Figure 1 Flowchart for the enrollment of the study population POI: premature ovarian insufficiency; TCM: traditional Chinese medicine; SDBS: kidney deficiency and bloodstasis syndrome; QBDS: Qi and blood deficiency syndrome.

Table 1 Comparison of serum hormone levels

Characteristic	SDBS group (n = 20)	QBDS group (n = 20)	P value
FSH (IU/L)	46.35±26.88	45.76±19.24	0.937
LH (IU/L)	16.16±9.61	14.61±7.84	0.580
E2 (pg/L)	27.35±10.12	35.55±7.16	0.005^a
P (nmol/L)	0.46±0.36	0.51±0.23	0.625
T (nmol/L)	0.47±0.25	0.42±0.21	0.546
PRL (nmol/L)	16.46±8.82	14.42±5.58	0.387
AMH (ng/mL)	0.59±0.29	0.38±0.22	0.016^b
FSH/LH (ratio)	2.96±0.72	3.35±0.75	0.104

Figure 2 Microbial community profiles of the gut microbiota in the SDBS and QBDS groups A: relative abundance at the phylum level; B: relative abundance at the genus level; C: the genera between the SDBS and QBDS groups differ significantly. G1 represents the SDBS group and G2 represents the QBDS group. SDBS: kidney deficiency and blood stasis pattern; QBDS: Qi and blood deficiency.

Figure 3 Metabolic pathways that differed significantly between the SDBS and QBDS groups SDBS: kidney deficiency and blood stasis pattern; QBDS: Qi and blood deficiency; G1 represents the SDBS group and G2 represents the QBDS group.

Figure 4 ROC curve for the model based on gut microbiome characteristics ROC: receiver operating characteristic.

References 40.

1.	Webber L, Davies M, Anderson R, et al. ESHRE guideline: management of women with premature ovarian insufficiency. Hum Reprod 2016; 31: 926-37.
2.	Anderson RA, Amant F, Braat D, et al. ESHRE guideline: female fertility preservation. Hum Reprod Open 2020; 2020: hoaa052.
3.	Tsiligiannis S, Panay N, Stevenson JC. Premature ovarian insufficiency and long-term health consequences. Curr Vasc Pharmacol 2019; 17: 604-9. DOI PMID
4.	Podfigurna-Stopa A, Czyzyk A, Grymowicz M, et al. Premature ovarian insufficiency: the context of long-term effects. J Endocrinol Invest 2016; 39: 983-90. DOI PMID
5.	Huang C, Guo T, Qin Y. Meiotic recombination defects and premature ovarian insufficiency. Front Cell Dev Biol 2021; 9: 652407.
6.	Kirshenbaum M, Orvieto R. Premature ovarian insufficiency (POI) and autoimmunity-an update appraisal. J Assist Reprod Genet 2019; 36: 2207-15.
7.	Szeliga A, Calik-Ksepka A, Maciejewska-Jeske M, et al. Autoimmune diseases in patients with premature ovarian insufficiency-our current state of knowledge. Int J Mol Sci 2021; 22: 2594.
8.	Wang C, Li Q, Ren J. Microbiota-immune interaction in the pathogenesis of gut-derived infection. Front Immunol 2019; 10: 1873. DOI PMID
9.	Kinashi Y, Hase K. Partners in leaky gut syndrome: intestinal dysbiosis and autoimmunity. Front Immunol 2021; 12: 673708.
10.	Wu J, Zhuo Y, Liu Y, et al. Association between premature ovarian insufficiency and gut microbiota. BMC Pregnancy Childbirth 2021; 21: 418.
11.	Li Z, Xu C. The fundamental theory of Traditional Chinese Medicine and the consideration in its research strategy. Front Med 2011; 5: 208-11.
12.	Chen ZG, Luo H, Xu S, et al. Study on the methodology of developing evidence-based clinical practice guidelines of Chinese medicine. Chin J Integr Med 2015; 21: 874-80.
13.	Liu MY, Yang W, Wang LY, et al. Clinical application evaluation of Guidelines for the diagnosis and treatment of common diseases of pediatrics in Traditional Chinese Medicine. Zhong Guo Zhong Yao Za Zhi 2017; 42: 3238-42.
14.	Li HF, Shen QH, Chen WJ, et al. Efficacy of Traditional Chinese Medicine tonifying kidney (Bushen) and activating blood (Huoxue) prescription for premature ovarian insufficiency: a systematic review and Meta-analysis. Evid Based Complement Alternat Med 2020; 2020: 1789304.
15.	Li F, Zhao C, Xia Z, et al. Computer-assisted lip diagnosis on Traditional Chinese Medicine using multi-class support vector machines. BMC Complement Altern Med 2012; 12: 127.
16.	Chen J, Wang S, Shen J, et al. Analysis of gut microbiota composition in lung adenocarcinoma patients with TCM Qi-Yin deficiency. Am J Chin Med 2021; 49: 1667-82.
17.	Zhang YL, Cai LT, Qi JY, et al. Gut microbiota contributes to the distinction between two Traditional Chinese Medicine syndromes of ulcerative colitis. World J Gastroenterol 2019; 25: 3242-55.
18.	Lin Z, Ye W, Zu X, et al. Integrative metabolic and microbial profiling on patients with spleen-Yang-deficiency syndrome. Sci Rep 2018; 8: 6619. DOI PMID
19.	Deng Z, Fu Z, Yan W, et al. The different effects of Chinese herb solid drink and lactulose on gut microbiota in rats with slow transit constipation induced by compound diphenoxylate. Food Res Int 2021; 143: 110273.
20.	Bolyen E, Rideout JR, Dillon MR, et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol 2019; 37: 852-7. DOI PMID
21.	Wu J, Zhuo Y, Liu Y, et al. Association between premature ovarian insufficiency and gut microbiota. BMC Pregnancy Childbirth 2021; 21: 418-25.
22.	Heintz-Buschart A, Wilmes P. Human gut microbiome: function matters. Trends Microbiol 2018; 26: 563-74. DOI PMID
23.	Sharon G, Sampson TR, Geschwind DH, et al. The central nervous system and the gut microbiome. Cell 2016; 167: 915-32. DOI PMID
24.	Cryan JF, O'Riordan KJ, Sandhu K, et al. The gut microbiome in neurological disorders. Lancet Neurol 2020; 19: 179-94. DOI PMID
25.	Qi X, Yun C, Pang Y, et al. The impact of the gut microbiota on the reproductive and metabolic endocrine system. Gut Microbes 2021; 13: 1-21. DOI PMID
26.	Thackray VG. Sex, microbes, and polycystic ovary syndrome. Trends Endocrinol Metab 2019; 30: 54-65.
27.	Miquel S, Martín R, Rossi O, et al. Faecalibacterium prausnitzii and human intestinal health. Curr Opin Microbiol 2013; 16: 255-61. DOI PMID
28.	Qiu X, Zhang M, Yang X, et al. Faecalibacterium prausnitzii upregulates regulatory T cells and anti-inflammatory cytokines in treating TNBS-induced colitis. J Crohns Colitis 2013; 7: e558-68.
29.	Zhou L, Zhang M, Wang Y, et al. Faecalibacterium prausnitzii produces butyrate to maintain Th17/Treg balance and to ameliorate colorectal colitis by inhibiting histone deacetylase 1. Inflamm Bowel Dis 2018; 24: 1926-40. DOI PMID
30.	Zafar H, Saier MH, Jr. Gut bacteroides species in health and disease. Gut Microbes 2021; 13: 1-20.
31.	Jandhyala SM, Talukdar R, Subramanyam C, et al. Role of the normal gut microbiota. World J Gastroenterol 2015; 21: 8787-803.
32.	Distrutti E, Monaldi L, Ricci P, et al. Gut microbiota role in irritable bowel syndrome: new therapeutic strategies. World J Gastroenterol 2016; 22: 2219-41.
33.	Suk KT, Kim DJ. Gut microbiota: novel therapeutic target for nonalcoholic fatty liver disease. Expert Rev Gastroenterol Hepatol 2019; 13: 193-204.
34.	Wu J, Ning Y, Tan L, et al. Characteristics of the vaginal microbiome in women with premature ovarian insufficiency. J Ovarian Res 2021; 14: 172. DOI PMID
35.	Lee S, Koh J, Chang Y, et al. Invariant NKT cells functionally link microbiota-induced butyrate production and joint inflammation. J Immunol 2019; 203: 3199-208. DOI PMID
36.	Ríos-Covián D, Ruas-Madiedo P, Margolles A, et al. Intestinal short chain fatty acids and their link with diet and human health. Front Microbiol 2016; 7: 185. DOI PMID
37.	Dalile B, Van Oudenhove L, Vervliet B, et al. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat Rev Gastroenterol Hepatol 2019; 16: 461-78. DOI PMID
38.	Jeong SY, Kang S, Hua CS, et al. Synbiotic effects of β-glucans from cauliflower mushroom and lactobacillus fermentum on metabolic changes and gut microbiome in estrogen-deficient rats. Genes Nutr 2017; 12: 31.
39.	Wu X, Kim MJ, Yang HJ, et al. Chitosan alleviated menopausal symptoms and modulated the gut microbiota in estrogen-deficient rats. Eur J Nutr 2021; 60: 1907-19.
40.	Min Z, Ge Z, Jinao D. Effect of Siwutang on diminished ovarian reserve in rats based on 16S rRNA sequencing of intestinal flora. Zhong Guo Shi Yan Fang Ji Xue Za Zhi 2022; 28: 25-32.

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