TABLE 2.

Association between estrogens and estrogen metabolites with fecal microbial alpha diversity (N = 110)^a

Estrogens and estrogen metabolites	Mutually adjusted modelb						Individual hormone modelc
	Observed ASVs		Faith's PD		Shannon index		Observed ASVs		Faith's PD		Shannon index
	(global p-value = 0.07)		(global p-value = 0.22)		(global p-value < 0.01)
	β	P value	β	P value	β	P value	β	P value	β	P value	β	P value
Parent Estrogens
Estrone	14.14	0.15	0.70	0.25	0.36	0.03	10.17	0.05	0.65	0.04	0.22	0.02
Unconjugated Estrone	—	—	—	—	—	—	6.33	0.40	0.39	0.39	0.19	0.15
Conjugated Estrone	—	—	—	—	—	—	10.31	0.02	0.67	0.01	0.20	0.01
Estradiol	1.72	0.86	−0.05	0.94	0.15	0.35	10.42	0.05	0.63	0.05	0.25	0.01
Unconjugated Estradiol	—	—	—	—	—	—	6.08	0.28	0.41	0.24	0.16	0.10
Conjugated Estradiol	—	—	—	—	—	—	5.21	0.05	0.31	0.05	0.11	0.02
2-Hydroxylation Pathway Metabolites
2-Hydroxyestrone	−3.42	0.84	0.42	0.70	−0.49	0.10	17.52	0.07	1.23	0.03	0.30	0.08
2-Hydroxyestradiol	11.76	0.13	0.51	0.29	0.30	0.02	6.39	0.38	0.34	0.43	0.19	0.13
2-Hydroxyestrone-3-methyl ether	1.35	0.90	−0.11	0.86	−0.05	0.77	10.78	0.14	0.46	0.30	0.14	0.27
2-Methoxyestrone	−1.28	0.90	−0.12	0.84	0.15	0.35	6.67	0.33	0.43	0.30	0.19	0.11
Unconjugated 2-Methoxyestrone	—	—	—	—	—	—	0.28	0.97	0.06	0.87	0.07	0.55
Conjugated 2-Methoxyestrone	—	—	—	—	—	—	1.55	0.68	0.13	0.57	0.06	0.34
2-Methoxyestradiol	-7.52	0.47	-0.27	0.68	-0.11	0.52	−6.49	0.42	−0.26	0.58	−0.07	0.64
Unconjugated 2-Methoxyestradiol	—	—	—	—	—	—	−2.83	0.75	−0.27	0.62	0.01	0.95
Conjugated 2-Methoxyestradiol	—	—	to	—	—	—	−5.75	0.31	−0.24	0.48	−0.06	0.56
4-Hydroxylation Pathway Metabolites
4-Hydroxyestrone	−5.58	0.59	−0.26	0.69	−0.24	0.17	9.62	0.13	0.50	0.19	0.16	0.15
4-Methoxyestrone	16.07	0.15	0.67	0.33	0.51	0.01	17.99	0.02	0.89	0.06	0.42	<0.01*
4-Methoxyestradiol	0.67	0.95	−0.30	0.66	0.14	0.45	−8.07	0.35	−0.74	0.16	−0.09	0.55
16-alpha-Hydroxylation Pathway Metabolites
Estriol	14.70	0.16	0.94	0.15	0.36	0.04	12.69	0.05	0.81	0.04	0.25	0.03
Unconjugated Estriol	—	—	—	—	—	—	−4.49	0.65	−0.28	0.64	0.08	0.65
Conjugated Estriol	—	—	—	—	—	—	10.81	0.04	0.69	0.03	0.21	0.02
16-alpha-Hydroxyestrone	−23.19	0.02	−0.99	0.10	−0.57	<0.01	−1.59	0.76	−0.01	0.97	−0.01	0.91
16-Ketoestradiol	8.26	0.44	0.13	0.85	0.19	0.28	5.89	0.36	0.28	0.47	0.11	0.35
16-Epiestriol	−4.55	0.60	−0.29	0.58	−0.09	0.53	7.15	0.24	0.37	0.31	0.13	0.25
17-Epiestriol	15.53	0.09	0.98	0.09	0.15	0.33	18.46	0.01	0.96	0.02	0.28	0.03

^aLinear regression model that includes all metabolites with additional adjustment for age and BMI; the missing BMI value of one woman was replaced by the median category; ASVs, amplicon sequence variants; Faith's PD, Faith’s phylogenetic diversity.

^bAs the concentration of the 5 conjugated metabolites are calculated as the difference between the combined estrogen measurement and the unconjugated estrogen measurement (e.g., conjugated estrone = estrone − unconjugated estrone), the unconjugated and conjugated analytes were not included in the mutually adjusted model.

^cThe False discovery rate (FDR) adjusted P value was calculated for the individual hormone models to adjust for multiple testing; *FDR adjusted P value ≤0.05; The P values present in the table are all normal P values.