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The gut microbiome is receiving considerable attention as a potentially modifiable risk factor and therapeutic target for numerous mental and neurological diseases.
This study aimed to explore and assess the difference in the composition of gut microbes and fecal metabolites between women with hypoactive sexual desire disorder (HSDD) and healthy controls.
We employed an online recruitment method to enroll “hard-to-reach” HSDD populations. After a stringent diagnostic and exclusion process based on DSM-IV criteria, fecal samples collected from 24 women with HSDD and 22 age-matched, healthy controls underwent microbiome analysis using 16S ribosomal RNA gene sequencing and metabolome analysis using untargeted liquid chromatography–mass spectrometry.
We found a decreased abundance of
Our analysis of fecal samples from women with HSDD and healthy controls identified significantly different gut microbes and metabolic signatures. These preliminary findings could be useful for developing strategies to adjust the level of human sexual desire by modifying gut microbiota.
Chinese Clinical Trial Registry ChiCTR1800020321; http://www.chictr.org.cn/showproj.aspx?proj=34267
Hypoactive sexual desire disorder (HSDD) is defined as a deficiency or absence of desire for sexual activity that causes marked distress or interpersonal difficulty and is not accounted for by another psychiatric condition, use of medications, or relationship problems [
In humans, sexual desire is regulated by key areas of the brain through the action of various neurotransmitters [
Human beings exist in a mutualistic relationship with their gut microbiota, a highly diverse and complex microbial ecosystem closely associated with various phenotypes and diseases [
Although this evidence suggests that there may be a connection between the composition of gut microbiota and sexual desire, our knowledge of the role of gut microbiota in sexual desire disorders is limited. We hypothesized that the fecal gut microbiota and metabolites of patients with sexual desire disorders differ from those of people without such disorders and that active metabolites and neurochemicals may be mediators between gut microbes and the sexual desire system.
Recruiting participants for microbial research is increasingly difficult as the number of projects competing for participants’ attention increases and response rates decline. In addition, women with desire disorder constitute a hard-to-reach population owing to fear and lack of trust in the study procedures or in research staff, especially in a more conservative society like China when compared with Western countries [
We conducted this study to investigate the composition of the gut microbiome and metabolite abundance in women with HSDD and to increase our understanding of the possible association between human sexual desire and gut microbiota and fecal metabolites.
From March 2019 to November 2019, we recruited subjects by posting advertisements on instant messenger applications and the information platform. In all advertisements, potential participants were automatically redirected to a study website that included a link to the survey and participant information including study details and information statement.
Potential recruits included women who had previously been diagnosed with suspected HSDD but not yet treated or who complained of decreased sexual desire, causing them to seek medical counseling, as well as volunteers who claimed to have normal sexual desire. No incentives were offered to responders. When requested, they were provided a brief report on their own gut microbial composition. All responders provided electronic written informed consent. All experimental protocols used in this study were approved by the Ethics Committee of Anhui Medical University and the relevant hospitals.
We collected information online from 157 premenopausal women and scheduled face-to-face diagnostic interviews and biological sample collection to identify women with generalized acquired HSDD. Incomplete questionnaires and responses that rejected further face-to-face interviews were not accepted by the system. A combination of a web-based questionnaire and structured interviews was used to collect information on demographic characteristics such as ethnicity, marital status, income, educational level, reproductive history, sexual partner relationships, sexual frequency, sexual dysfunction, and the presence and treatment of related diseases.
Subsequently, we performed high-throughput 16S ribosomal RNA gene sequencing and untargeted liquid chromatography–mass spectrometry metabolomic analysis of stool samples from the 26-member HSDD cohort and 26 healthy controls (for all survey measures and analysis methods, see the Methods section in
A flowchart showing the inclusion and exclusion processes is presented in
Inclusion and exclusion processes. HSDD: hypoactive sexual desire disorder; LC-MS: liquid chromatography–mass spectrometry; NHSD: no history of sexual dysfunction.
Demographic and other sample data at baseline.
Characteristic | HSDDa (n=24) | NHSDb (n=22) | |
Age (years), mean (SD) | 33.8 (4.5) | 33.9 (4.0) | .91 |
BMI (kg/m2), mean (SD) | 27.1 (3.6) | 26.3 (3.3) | .27 |
College or beyond, n | 17 | 16 | .89 |
FSFI-Dc score, mean (SD) | 3.2 (0.9) | 8.6 (1.0) | .01 |
CES-Dd score, mean (SD) | 10.3 (4.9) | 10.9 (4.6) | .55 |
RBCe (×1012/L), mean (SD) | 4.3 (0.7) | 4.1 (0.4) | .06 |
WBCf (×109/L), mean (SD) | 6.9 (1.7) | 6.5 (1.7) | .28 |
PLTg (×1012/L), mean (SD) | 169.4 (44.8) | 154.0 (35.9) | .04 |
FSHh,i (mIU/mL), mean (SD) | 6.3 (3.0) | 6.3 (2.9) | .93 |
LHi,j (mIU/mL), mean (SD) | 5.3 (3.4) | 5.9 (3.7) | .67 |
Estradioli (pg/mL), mean (SD) | 48.1(9.3) | 50.6 (6.5) | .09 |
Total Ti,k (ng/mL), mean (SD) | 0.5 (0.3) | 0.5 (0.2) | .86 |
aHSDD: hypoactive sexual desire disorder.
bNHSD: no history of sexual dysfunction.
cFSFI-D: Female Sexual Function Index desire domain.
dCES-D: Center for Epidemiologic Studies Depression Scale.
eRBC: red blood cell.
fWBC: white blood cell.
gPLT: platelet.
hFSH: follicle-stimulating hormone.
iDue to missing data, the group sizes differ for hormonal data: HSDD group, n=20; NHSD group, n=14.
jLH: luteinizing hormone.
kT: testosterone.
In our investigation, 1753 operational taxonomic units were identified from sequenced specimens with 97% sequence similarity. Different operational taxonomic unit–based diversity indexes were used to assess the bacterial composition within each sample (the α-diversity). Compared to the NHSD group, the HSDD cohort was characterized by a higher number of observed species and higher Shannon and Chao 1 indexes (
Gut microbial characteristics of women with hypoactive sexual desire disorder (HSDD) or with no history of sexual dysfunction (NHSD), based on (A) α-diversity analysis of 3 indexes (observed species, shannon, and Chao 1); (B) β-diversity analysis, providing unweighted and weighted principal coordinate (PC) plots; (C) component proportion of bacterial phylum in each group; (D) the ratio between HSDD and NHSD on the logarithmic scale. All QFDR<0.05.
At the phylum level, the most abundant taxa were
In the fecal metabolome analysis, 1168 metabolites were quantified. Differential metabolite volcanic maps show that the fecal metabolic phenotype of women with HSDD was significantly different than that of women with NHSD (
Fecal metabolites characteristics of women with hypoactive sexual desire disorder (HSDD) and women with no history of sexual dysfunction (NHSD), displayed as (A) volcano plots showing the differentially accumulated (log2[fold change] and significantly changed (-log10[pvalue] fecal metabolites; (B) principal component (PC) analysis showing grouped discrimination; (C) functions and pathways of these metabolites using the KEGG database, where the differential metabolites are annotated on 12 different KEGG metabolic pathways; (D) Lefse and linear discriminant analyses showing differences in taxonomic composition; (E) receiver operating characteristic (ROC) curve. AUC: area under the curve; TRP: tryptophan.
To further identify the specific bacterial components associated with HSDD, we used a standard microbiota analysis tool, LefSe; 8 taxa were identified as key biomarkers (
To identify and quantify the potential of microbial and metabolic biomarkers for HSDD, we performed a receiver operating characteristic curve analysis using the relative abundance of the
A Spearman’s rank correlation test was performed to explore the correlations between gut microbes, fecal metabolites, and clinical characteristics. The altered bacterial genera were generally associated with differential metabolites (
These results suggest significant differences in the composition of fecal microbiota between controls and women with HSDD. We observed a significantly higher quantity of
There is considerable evidence that gut microorganisms modulate the metabolism of dopamine, 5-HT, and noradrenaline in the brain [
The analysis of fecal metabolic components has received considerable attention since these biomolecules reflect genetic and environmental effects and also act to connect the health of the host and its symbiotic microorganisms [
The systematic exclusion of alternative diagnoses by structured interviews and the use of rigorous differential diagnosis criteria based on the DSM-IV resulted in a representative cohort of individuals with generalized acquired HSDD, avoiding various genital disorders existing in men or elderly women, rather than the sexual desire problem of “central effect.” In addition, although we reported Center for Epidemiologic Studies Depression Scale 20 scores, estradiol, testosterone, and sex hormone-binding globulin, in fact, the cause of HSDD is multifactorial and variable; changes in hormones, stress, depression, present sexual experiences, past history of abuse, total well-being, sexual condition of the sexual partner, and relationship factors may also be crucial causes of sexual desire disorder [
Given the increased popularity of online media and information platforms, many researchers are using web-based tools to recruit participants for medical, psychological, and sociological research studies (especially for stigmatized and hard-to-reach groups). Previous studies have shown that online methods can successfully recruit and manage people who are humiliated or discriminated against because of race, sexual orientation, or mental health status [
There are several potential limitations of our research. First, our online recruitment methods relied on convenience samples, and determining the source population limits the external validity of findings. When it comes to sensitive issues, determining adequate compensation and ensuring confidentiality continue to be important concerns. Second, gut microorganisms and metabolites are affected by a variety of factors, including geography, daily diet, and genetic variation [
This study addressed a number of gaps. We identified numerous microbial genera, including
A better understanding of the microbiota’s role in the gut-brain-libido axis may lead to the identification of novel drug targets and management measures to improve sexual health. Much work remains to be performed in determining the role and mechanisms of the gut microbiota in human sexual desire.
Supplementary methods.
Heat map. (a) Heat map of the Spearman’s rank correlation coefficient of differential bacterial genus, differential metabolites and HSDD clinical characteristics. (b) Heatmaps showing altered bacterial genus were generally associated with differential fecal metabolites. The statistical significance was denoted on the squares (#p < 0.05; ##< 0.01).
γ-aminobutyric acid
hypoactive sexual desire disorder
no history of sexual dysfunction
short-chain fatty acids
The authors would like to thank all participants. We also thank the researchers from Anhui Medical University, as well as engineers, nurses, and doctors. This work was supported by the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (grant number 2019PT310002).
None declared.