Abstract Introduction Hyposexual desire disorder (HSDD) is a common female sexual health problem. HSDD mainly refers to women's continuous lack of sexual fantasy or desire for sexual activities, accompanied by obvious personal pain or affecting the partnership. In humans, sexual desire is regulated by a variety of neurotransmitters in key areas of the brain. Norepinephrine, dopamine, melanocortin, oxytocin and vasopressin mediate excitability, while serotonin, opioids, prolactin and endogenous cannabinoid system mediate inhibition. HSDD may be related to neuropsychological state of increased inhibition or decreased excitation, or both. There is a close relationship between gut microbiota and a variety of mental and neurological diseases. The changes of gut microbiota richness and diversity affect the functions of 5-hydroxytryptamine, norepinephrine and dopaminergic nervous systems in the brain, and these pathways and molecules have been proved to be closely related to the level of human sexual desire. At present, the understanding of the role of gut microbiota in the regulation of sexual desire and the mechanism of HSDD is limited. Objective In order to study the composition of gut microbiota and fecal metabolites in HSDD women, and increase the understanding of the possible relationship between low sexual desire and intestinal microbiota, this study hypothesized that the composition of intestinal microorganisms and fecal metabolites in HSDD patients was different from that in normal people. Methods We recruited and diagnosed HSDD women through Case-Control study, and performed the 16S rRNA sequencing, non targeted LC-MS metabonomics detection and targeted SCFAs quantitative detection of intestinal microorganisms to explore and evaluate the differences of gut microbiota and fecal metabolites composition between HSDD women and control group. Results In this study, 24 women with HSDD and 22 women without history of sexual dysfunction (NHSD) were included. The 16S rRNA gene sequencing of 46 fecal samples showed that the richness and diversity of intestinal flora in HSDD women were higher than those in NHSD women, and there were significant differences in the composition of gut microbiota between the two groups. At the genus level, Bifidobacterium, Lactobacillus, Sphingomonas, Phenylbacillus, Corynebacterium and some unclassified actinomycetes were enriched in the feces of HSDD women, while Ruminococcus were enriched in the feces of NHSD women. The results of non-targeted metabonomics of fecal samples showed that there were significant differences between HSDD and NHSD women in fecal metabolic phenotype. The main metabolites included histamine, deoxycorticosterone, tryptamine, tyramine, 6-methylquinoline, etc. The results of targeted SCFAs quantitative analysis showed that the content of butyric acid in feces of HSDD group was significantly higher than that of NHSD group. Spearman correlation analysis showed that the difference of gut microbiota and fecal metabolites between the two groups were associated with clinical characteristics including FSFI-D score. Conclusions The composition of gut microbiota and metabolites in HSDD women is different from that in NHSD women. The effect of characteristic bacteria and metabolites on the function of neurotransmitter system may be part of the pathogenesis of HSDD. Further studies may bring new theories of the gut microbiota brain sexual desire axis. Disclosure No