Table 1. Summary of human studies regarding sex differences in gut microbiota.
| Country | Participant (n) | M:F ratio (%) | Age (y) | Study method | Findings with regard to sex differences | Reference |
|---|---|---|---|---|---|---|
| France, Denmark, Germany, Netherlands, United Kingdom | 91 | N/A | 7–52 | Fluorescent in situ hybridization using 18 phylogenetic probes | According to the principle component analysis, there was no significant grouping of samples with respect to sex, regardless of whether analyzing the entire cohort of samples or analyzing by each country. | Lay et al (2005) [9] |
| France, Germany, Italy, Sweden | 230 | N/A | 20–50 | 14 Group- and species-specific 16S rRNA-targeted oligonucleotide probes/fluorescence in situ hybridization analysis | ↑Bacteroides-Prevotella group in males than in females. | Mueller et al (2006) [10] |
| At the species level, no sex differences were observed for Bacteroides vulgatus and Bacteroides putredinis. | ||||||
| There was no detectable sex effect for any of the other microbial groups. | ||||||
| China | 7 | 43:57 | 1.5–95 | Bacteroides spp. group-specific DGGE profiling | ↑Bacteroides thetaiotaomicron in males than in females. | Li et al (2008) [11] |
| Human Microbiome Project (HMP) Cohort | 300 | 50:50 | 18–40 | 16S rRNA gene sequencing/454 FLX (Roche) | Sex was associated with community types identified in the stool. | Ding and Schloss (2014) [12] |
| Males were 3 times more likely than females to harbor stool community type D. | ||||||
| USA (white 85.4%, black 12.2%, other 2.4%) | 82 | 62:38 | 30–8 | 16S rRNA gene sequencing/454 FLX (Roche) | Sex was significantly associated with the overall gut microbiome composition. | Dominianni et al (2015) [13] |
| ↓Bacteroidetes in females. | ||||||
| The relationship between BMI and gut microbiota composition was significant in females, but not in males. | ||||||
| ↓Shannon-diversity indices for overweight and obese subjects compared with normal-weight subjects in females, but no difference in males. | ||||||
| USA | 200 individuals with enteric infection, 75 healthy individuals | 53:47 | 0–10 (n=91) | 16S rRNA gene sequencing/454 GS Junior Titanium (Roche) | Sex was significantly associated with the overall gut microbiota composition: At the genus level, ↑Bacteroides in females, ↑Escherichia in males. | Singh and Manning (2016) [14] |
| 11–18 (n=32) | There was no sex difference in gut microbiota in healthy individuals. | |||||
| 19–49 (n=84) | There was significant difference between sexes in individuals with enteric infection: ↑Enterobacteriaceae among 11 different features in males, ↑Bacteroidaceae among 43 different features in females. | |||||
| 50–69 (n=45) | ||||||
| ≥70 (n=12) | ||||||
| Spain | 75 | 52:48 | Postmenopausal females 60.31±1.40, age-matched males 61.15±1.27 | 16S rRNA gene sequencing/MiSeq (Illumina) | The microbiota diversity and overall community composition were not significantly different between sexes. | Haro et al (2016) [15] |
| ↑Veillonella and Methanobrevibacter at the genus level, Bacteroides plebeius and Coprococcus catus at the species level in males. | ||||||
| ↑Bilophila at the genus level, Bacteroides caccae at the species level in females. | ||||||
| There were no differences at the phylum level and in the F/B ratio between sexes when considered independently of the BMI. | ||||||
| The F/B ratio was higher when BMI ≤33 kg/m2 and lower when BMI >33 kg/m2 in males compared with females. | ||||||
| ↓Bacteroides at the genus level in males when BMI > 33 kg/m2. | ||||||
| Italy | 40 | 50:50 | Normal-weight males 48.7±10.2 and females 51.7±8.3, obese males 53.8±7.7 and females 51.3±6.7 | 16S rRNA gene sequencing/MiSeq (Illumina) | There was no difference in LAM between the sexes. | Borgo et al (2018) [16] |
| ↑α-diversity in MAM in females. | ||||||
| ↑Actinobacteria and Lactobacillales in MAM of females. | ||||||
| ↑Bifidobacterium spp. and Streptococcaceae. ↓Veillonellaceae and unclassified Clostridia in MAM of females. | ||||||
| China | 551 | 47:53 | Underweight males 21.5±5.5, females 38.0±25.6, normalweight males 37.8±17.3 and females 35.6±14.3, overweight males 41.7±15.9 and females 38.1±12.6, obese males 34.7±12.5 and females 35.5±12.7 | 16S rRNA gene sequencing/MiSeq (Illumina) | There was no significant overall difference in gut microbiota between the sexes. | Gao et al (2018) [17] |
| ↑α-diversity in females. | ||||||
| Regardless of the BMI, there were no significant differences at the phylum, class, order, or family levels between the sexes, but | ||||||
| ↑Ruminococcus at the genus level in females. | ||||||
| In obese subjects, at the genus level, | ||||||
| ↑Bifidobacterium, Coprococcus, and Dialister in females, | ||||||
| ↓Phascolarctobacterium in females, | ||||||
| ↑Fusobacterium in males. | ||||||
| In underweight subjects, at the genus level, ↓Sutterella in males. | ||||||
| Japan | 277 | 50:50 | 20–89 | 16S rRNA gene sequencing/MiSeq (Illumina) | There was no significant difference in α-diversity between males and females. | Takagi et al (2019) [18] |
| ↑Genera Prevotella, Megamonas, Fusobacterium, and Megasphaera in males. | ||||||
| ↑Genera Bifidobacterium, Ruminococcus, and Akkermansia in females. | ||||||
| Hard stools were higher in females, loose to liquid stools were higher in males. | ||||||
| Netherlands | 1,135 | 42:58 | 18–81 | Shotgun sequencing | Sex was significantly associated with the overall gut microbiota composition, 12 microbial species, and 43 metabolic pathways. | Sinha et al (2019) [19] |
| ↑Akkermansia muciniphila in females. | ||||||
| ↑Richness of antibiotic resistance genes in females. |
M: male, F: female, NA: not available, DGGE: denaturing gradient gel electrophoresis, BMI: body mass index, F/B ratio: firmicutes/bacteroidetes ratio, LAM: lumen-associated microbiota, MAM: mucosa-associated microbiota.