Distinct gut and vaginal microbiota profile in women with recurrent implantation failure and unexplained infertility

Abstract

Background Female reproductive tract dysbiosis impacts implantation. However, whether gut dysbiosis influences implantation failure and whether it accompanies reproductive tract dysbiosis remains scantly explored. Herein, we examined the gut-vaginal microbiota axis in infertile women. Methods We recruited 11 fertile women as the controls, and a cohort of 20 infertile women, 10 of whom had recurrent implantation failure (RIF), and another 10 had unexplained infertility (UE). Using amplicon sequencing, which employs PCR to create sequences of DNA called amplicon, we compared the diversity, structure, and composition of faecal and vaginal bacteria of the controls with that of the infertile cohort. Of note, we could only sequence 8 vaginal samples in each group (n = 24/31). Result Compared with the controls, α-diversity and β-diversity of the gut bacteria among the infertile groups differed significantly (p < 0.05). Taxa analysis revealed enrichment of Gram-positive bacteria in the RIF group, whereas Gram-negative bacteria were relatively abundant in the UE group. Strikingly, mucus-producing genera declined in the infertile cohort (p < 0.05). Hungatella, associated with trimethylamine N-oxide (TMAO) production, were enriched in the infertile cohort (p < 0.05). Vaginal microbiota was dominated by the genus Lactobacillus, with Lactobacillus iners AB-1 being the most abundant species across the groups. Compared with the infertile cohort, overgrowth of anaerobic bacteria, associated with vaginal dysbiosis, such as Leptotrichia and Snethia, occurred in the controls. Conclusion The gut microbiota had little influence on the vaginal microbiota. Gut dysbiosis and vaginal eubiosis occurred in the infertile women, whereas the opposite trend occurred in the controls.

Interplay between PCOS and microbiome: The road less travelled

“…When the mucus barrier is breached, gut bacteria and other microbe‐associated molecular patterns (MAMPs) can directly communicate with toll‐like receptors (TLRs) in gut intestinal mucosa like paneth cells. This triggers an inflammatory cascade that promotes localised NF‐κβ activation, IL‐6 is released systemically, prompting an immunological response that can ultimately led to regional and systemic inflammation thereby affecting LH‐induced ovulation, FSH‐induced estrogen and progesterone release and thus, may cause infertility problem through these mechanisms 49 …”

“…44,45 This is characterised by epithelial cell destruction and cause infertility problem through these mechanisms. 49 Increased number of mucin-degrading bacteria, such as Prevotella, and reduced numbers of bacteria like Bacteroidales S23-7, Clostridiales, Ruminococcus, and Lachnospiraceae that produce butyrate have been observed in dysbiosis study of PCOS patients. 50 An increased abundance of Gardnerella as well as Mycoplasma also has a negative impact on ovarian function, as exemplified by diminished ovarian reserve and ovarian endocrine disruption, resulting in menstrual problems.…”

The definition of unexplained infertility: A systematic review

“…Of the remaining 375 papers, 117 did not classify a definition of unexplained infertility. As a result, a total of 258 primary research papers with full text available were included …”

Recurrent implantation failure: A comprehensive summary from etiology to treatment

“…It may also be involved in embryo implantation by affecting the immune system, coagulation system, and endometriosis pathology (113)(114)(115). Patients with RIF display abnormal gut microbiota (116), but the relationship between gut microbiota and implantation failure needs to be further investigated.…”