Association Analysis And Mechanism Study Of Gut Microbiota And Sexual Desire Disorder In Women

Background.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.The occurrence of HSDD can damage women's body image and self-confidence,and may damage sexual partners and family relationships.Large sample studies have shown that about 8% to 13.6% of women meet the diagnostic criteria of HSDD.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,GABAergic 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,and the neurotransmitter system was the bridge between gut microbiota and sexual desire regulation system.Methods.In the first part of the study,we recruited and diagnosed HSDD women through Case-Control study,and performed the 16 S r RNA 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.In the second part of the study,fecal bacteria transplantation was used to intervene the gut microbiota of rats.The gut microbiota of HSDD female and NHSD female were transplanted into the female mating experimental model rats,and the rat model of bacterial flora transplantation of HSDD female was established.By observing the sexual behavior of rats and quantitatively measuring the concentration of main neurotransmitters and their metabolites in prefrontal cortex of model rats,the effect of HSDD flora transplantation on the sexual desire level of rats was studied,and its neuroendocrine mechanism was explored.Results.(1)In the first part of the study,24 women with HSDD and 22 women without history of sexual dysfunction(NHSD)were included.The 16 S r RNA 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,Marseillaria,Porphyromonas and some unclassified actinomycetes were enriched in the feces of HSDD women,while Ruminococcus were enriched in the feces of NHSDwomen.(2)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,tetrahydrocortisone,6-methylquinoline,etc.(3)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.(4)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.(6)In the second part of the study,the 16 S r RNA gene sequencing results of fecal microorganisms in HSDD-FMT group and NHSD-FMT group showed that the richness and diversity of gut flora in HSDD-FMT group were higher than that in NHSD-FMT group.At the genus level,the abundance of Ruminococcus in NHSD-FMT group was higher than that in HSDD-FMT group,while the abundance of Staphylococcus in NHSD-FMT group was lower than that in HSDD-FMT group.This reflects the overall diversity of gut microflora in HSDD and NHSD women,and some of the differences are reflected in the recipient rats.(7)The results of sexual behavior experiment showed that there were significant differences in lordosis and solicitations behaviors between HSDD-FMT and NHSD-FMT rats,and between HSDD-FMT and model control rats.This reflects the decreased sexual desire level of female rats after receiving the fecal flora transplantation of HSDD female rats.(8)The quantitative results of monoamine neurotransmitters and their metabolites showed that compared with NHSD-FMT group,the concentrations of 5-HT and 5-HIAA in the brain PFC region of HSDD-FMT group increased,while the concentration of NE decreased.In addition,compared with NHSD-FMT group,the ratio of 5-HIAA / 5-HT in brain of HSDD-FMT group was increased,indicating that the conversion rate of 5-HT was increased.This reflects that the gut microbiota of HSDD transplant female affects the levels of monoamine neurotransmitters including 5-HT and their metabolites in PFC of recipient rats.Conclusions.(1)In this study,the composition of gut microbiota in HSDD women is different from that in NHSD women.The abundance of bifidobacteria and Lactobacillus increased,while Ruminococcus decreased,which may be the characteristic of HSDD.(2)The levels of various intestinal metabolites including histamine,deoxycorticosterone,6-methylquinoline,tryptamine and butyric acid in the feces of HSDD patients were different from those of NHSD women.These metabolic differences are related to the composition of intestinal flora,and may play an important role in the pathogenesis of HSDD.The mechanism may involve tryptophan metabolism,histidine metabolism,neuroactive ligand receptor interaction and other metabolic pathways.(3)In this study,we established a rat model of HSDD female flora transplantation,and found that the sexual desire level of female rats was decreased after receiving HSDD flora transplantation.The overall diversity of gut microflora in HSDD and NHSD women was different,and some of the differences were reflected in the recipient rats.The effect of characteristic bacteria and metabolites on the function of monoamine neurotransmitter system may be part of the pathogenesis of HSDD.