Investigation of the causal relationship between gut microbiota and thyroid cancer

doi:10.3760/cma.j.cn371439-20250823-00032

Abstract

Abstract:

Objective To explore the causal relationship between gut microbiota and thyroid cancer using Mendelian randomization （MR） analysis. Methods An MR study was conducted using summary data from genome-wide association studies （GWAS） of gut microbiome and thyroid cancer， and the local microbiome sequencing data was used to validate the findings. GWAS summary data of gut microbiota were obtained from the MiBioGen consortium （n=18 340）， served as exposure. The summary data of thyroid cancer were obtained from the UK Biobank （649 cases and 431 controls）， served as outcome. The inverse-variance weighting （IVW） method was used as the primary analysis method， with assessments of heterogeneity and horizontal pleiotropy conducted. From June 28， 2024 to July 31， 2024， a total of 20 thyroid cancer patients （thyroid cancer group） and 20 healthy controls （healthy control group） were recruited as research subjects at Affiliated Yantai Yuhuangding Hospital of Qingdao University. Fecal samples from all participants were collected and subjected to 16S rRNA gene sequencing. Results Five bacterial genera were identified with potential causal relationship with thyroid cancer. Paraprevotella （IVW OR=4.72， 95%CI： 1.27-17.56， P=0.021） and Eubacterium coprostanoligenes （IVW OR=5.96， 95%CI： 1.27-28.01， P=0.024） were causally associated with an increased risk of thyroid cancer， while Blautia （IVW OR=0.10， 95%CI： 0.01-0.97， P=0.046）， Parasutterella （IVW OR=0.25， 95%CI： 0.07-0.88， P=0.030）， and Prevotella_9 （IVW OR=0.21， 95%CI： 0.07-0.68， P=0.009） were causally associated with a decreased risk of thyroid cancer. Microbiome sequencing results indicated that compared with the healthy control group， the relative abundance of Paraprevotella [0.41 （0.03， 1.23） vs. 0.06 （0.01， 0.23）， U=84.50， P=0.038] and Eubacterium coprostanoligenes [0.93 （0.43， 2.23） vs. 0.42 （0.09， 1.20）， U=85.50， P=0.041] was significantly higher in the thyroid cancer group， with statistically significant differences； while those of Blautia [0.35 （0.26， 0.57） vs. 0.56 （0.35， 1.03）， U=90.00， P=0.062]， Parasutterella [0.18 （0.13， 0.68） vs. 0.43 （0.13， 1.07）， U=117.00， P=0.357]， and Prevotella_9 [0.19 （0.11， 3.82） vs. 1.23 （0.17， 12.10）， U=93.50， P=0.079] was reduced， although the differences did not reach statistical significance. Conclusions Five bacterial genera may have causal associations with thyroid cancer. Among them， Paraprevotella and Eubacterium coprostanoligenes are associated with an increased risk of thyroid cancer， while Blautia， Parasutterella， and Prevotella_9 are linked to a decreased risk of thyroid cancer. Local microbiome sequencing results reveal that Paraprevotella and Eubacterium coprostanoligenes may contribute to the pathogenesis of thyroid cancer， whereas Blautia， Parasutterella， and Prevotella_9 may exert protective effects， although confirmation through larger-scale studies is required.

Key words: Gastrointestinal microbiome, Thyroid neoplasms, Mendelian randomization analysis, Causality

Liu Lujia, Wang Yukun, Zheng Haitao. Investigation of the causal relationship between gut microbiota and thyroid cancer[J]. Journal of International Oncology, 2026, 53(4): 193-200.

Figures/Tables 8

References 31

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菌属	SNP （个）	方法	OR值（95%CI）	P值	Cochran's Q检验		多效性检验		F值（中位数）
菌属	SNP （个）	方法	OR值（95%CI）	P值	Q值	P_Q值	Egger截距	P_截距值	F值（中位数）
Paraprevotella	3	MR Egger	6.94（2.95~16.10）	0.672	0.11	0.740	-0.23	0.780	21.74
		IVW	4.72（1.27~17.56）	0.021	0.24	0.887
		加权中位数	5.62（1.08~29.18）	0.040
		简单模式	6.02（0.84~43.05）	0.216
		加权模式	6.07（0.98~37.50）	0.192
产粪甾醇真杆菌	4	MR Egger	8.26（1.17~18.50）	0.182	0.56	0.757	-0.26	0.278	23.33
		IVW	5.96（1.27~28.01）	0.024	2.73	0.435
		加权中位数	4.07（0.55~30.27）	0.170
		简单模式	3.06（0.16~59.05）	0.513
		加权模式	2.88（0.14~58.73）	0.542
布劳特菌属	4	MR Egger	0.55（0.16~1.37）	0.715	4.35	0.113	-0.46	0.620	19.81
		IVW	0.10（0.01~0.97）	0.046	5.09	0.166
		加权中位数	0.10（0.01~1.03）	0.052
		简单模式	0.04（0.00~1.87）	0.199
		加权模式	0.07（0.00~2.43）	0.238
Parasutterella	6	MR Egger	0.27（0.04~0.73）	0.276	4.82	0.307	-1.22	0.244	22.75
		IVW	0.25（0.07~0.88）	0.030	7.06	0.216
		加权中位数	0.39（0.09~1.63）	0.196
		简单模式	0.39（0.04~4.00）	0.462
		加权模式	0.39（0.04~3.73）	0.454
普雷沃菌属_9	5	MR Egger	0.02（0.14~0.63）	0.608	3.48	0.324	0.17	0.755	20.30
		IVW	0.21（0.07~0.68）	0.009	3.61	0.461
		加权中位数	0.23（0.05~1.07）	0.062
		简单模式	0.10（0.01~1.05）	0.128
		加权模式	0.52（0.05~4.95）	0.599

基线资料	甲状腺癌组（n=20）	健康对照组（n=20）	t/χ²/U值	P值
年龄（岁，$\bar{x} \pm s$）	40.0±11.6	41.2±10.3	-0.31	0.757
性别[例（%）]
男	6（30）	8（40）	0.44	0.741
女	14（70）	12（60）	0.44	0.741
BMI（kg/m²，$\bar{x} \pm s$）	25.28±3.25	24.91±2.55	0.37	0.714
TSH[mIU/L，M（Q₁，Q₃）]	2.36（1.51，2.93）	1.61（0.98，2.95）	154.50	0.218
FT₄（pmol/L，$\bar{x} \pm s$）	15.17±2.28	15.80±2.05	-0.79	0.438
FT₃（pmol/L，$\bar{x} \pm s$）	4.89±0.66	5.00±0.47	-0.51	0.617
TGAb（IU/ml，$\bar{x} \pm s$）	12.83±2.83	12.66±2.26	0.17	0.867
TPOAb（IU/ml，$\bar{x} \pm s$）	13.71±12.74	10.30±8.03	0.82	0.420
TRAb（IU/L，$\bar{x} \pm s$）	0.93±0.23	0.97±0.20	-0.52	0.606
TG[ng/ml，M（Q₁，Q₃）]	18.21（6.69，32.71）	22.08（6.42，52.66）	182.00	0.626

α多样性指数	甲状腺癌组（n=20）	健康对照组（n=20）	U值	P值
Chao1	500.34（457.71，576.50）	520.90（370.50，586.85）	144.00	>0.999
Shannon	6.18（5.64，6.55）	6.24（5.55，6.87）	131.00	0.658
Simpson	0.95（0.94，0.97）	0.96（0.93，0.98）	125.50	0.518

菌属	甲状腺癌组（n=20）	健康对照组（n=20）	U值	P值
Paraprevotella	0.41（0.03，1.23）	0.06（0.01，0.23）	84.50	0.038
产粪甾醇真杆菌	0.93（0.43，2.23）	0.42（0.09，1.20）	85.50	0.041
布劳特菌属	0.35（0.26，0.57）	0.56（0.35，1.03）	90.00	0.062
Parasutterella	0.18（0.13，0.68）	0.43（0.13，1.07）	117.00	0.357
普雷沃菌属_9	0.19（0.11，3.82）	1.23（0.17，12.10）	93.50	0.079