Sex differences and hormonal effects on gut microbiota composition in mice

Figures & data

Figure 1. Sex differences in gut microbiota composition in 89 different inbred strains of mice. (A) Columns represent the average relative abundance of microbial phyla within 89 matched strains of male (n = 348) and female (n = 341) mice arranged in the same order. (B) Procrustes plot comparing β diversity between females and males of the same strains. The Bray-Curtis distances between the genders vary across the strains (M² = 0.89, p < 0.001), highlighting the differences in microbial composition between sexes. (C) Bray-Curtis dissimilarity metric plotted in PCoA space comparing the gender microbial communities from different genders (89 matched strains). Each circle representing a different strain colored according to the gender. The first 3 principal components (PC1, PC2 and PC3) are shown, with the amount of variation explained are reported for each axes. Both sex and strain effects account for PC1 and PC3 variations (p < 0.0001, F test) and PC2 variation is explained only by strain effect (p < 0.001, F test). (D) Linear discriminant analysis (LDA) coupled with effect size measurements identified the most differentially abundant genus level taxa between female and male mice from 89 matched strains.

Table 1. The effect of sex on gut microbiota composition in HMDP strains.

		Relative abundance (%, Mean values ± SEM)
Strain	Taxonomy	Females	Males	p-value (adjusted)^*
BXD45/RwwJ	Allobaculum	1.33 (±0.65)	11.12 (±1.70)	0.0244
	Clostridiaceae	2.86 (±1.13)	15.65 (±1.52)	0.0025
	Rikenellaceae	0.014 (±0.002)	0.002 (±0.001)	0.0300
	S24-7	44.16 (±2.88)	29.02 (±2.09)	0.0406
	SMB53	1.44 (±0.10)	0.37 (±0.09)	0.0022
BXD85/Rww	Akkermansia	0.02 (±0.01)	37.8 (±1.11)	0.0029
	Roseburia	0.09 (±0.03)	0.52 (±0.05)	0.0178
	Allobaculum	0.003 (±0.002)	7.00 (±0.97)	0.0004
C57BL/6	Coprococcus	1.53 (±0.07)	0.69 (±0.05)	0.0270
	Bacteroides	8.02 (±1.65)	0.01 (±0.01)	0.0040
C3H/He	Akkermansia	0.01 (±0.004)	23.14 (±2.40)	0.0046
	Coprobacillus	0.11 (±0.03)	0.64 (±0.08)	0.0252
	Ruminococcus	0.16 (±0.03)	0.46 (±0.05)	0.0340
	Sutterella	0	8.94 (±1.75)	0.0302
BXD55/RwwJ	Lachnospiraceae	2.77 (±0.23)	1.51 (±0.22)	0.0490
AXB19a/PgnJ	Turicibacter	0.19 (±0.04)	0.01 (±0.008)	0.0450
BXD79/RwwJ	Lachnospiraceae	1.59 (±0.20)	6.09 (±0.93)	0.0013
	Dorea	0.25 (±0.08)	0.01 (±0.004)	0.0149
	Coprococcus	2.87 (±0.09)	0.52 (±0.78)	0.0167
	Roseburia	2.76 (±0.81)	0.32 (±0.14)	0.0187

Note.

* P value were adjusted using Benjamini-Hochberg FDR.

Figure 2. Principal coordinate analysis (PCoA) plot of unweighted UniFrac distances between male and female mice. C57BL/6J, C3H/HeJ, and DBA/2J strains fed a normal chow or high fat diets were studied as described in the text. PC1, PC2, and PC3 values for each mouse sample are plotted with the percent variation explained by each PC is shown in parentheses. (B) Examples of sex-by-diet interactions with 5 taxa in female and male from C57BL/6J and DBA/2J mice fed with chow or high fat diets. P values from MANOVA analysis are shown for sex, diet and sex-by-diet interactions (int).

Figure 3. The effect of gonadectomy in C57BL/6J, C3H/HeJ and DBA/2J mice. (A) Principal component analysis between male and female mice in normal chow or high fat/high-sucrose diet (B) from C57BL/6J, C3H/HeJ, and DBA/2J strains.(B) Bile acids measurements from gallbladder in male and female C57BL/6J mice on chow and HF/HS diet. Significance of differences was defined using unpaired T test with Holm-Sidak's correction for multiple hypothesis. *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001. DC, deoxycholic; GDX, gonadectomized.