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 genusLactobacillus,withLactobacillus 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 asLeptotrichia 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.

PCOS is a prevalent endocrine disorder among women of reproductive age, characterized by hormonal imbalances and metabolic disturbances. This study explores the correlation between gut microbial β-glucuronidase and β-glucosidase and PCOS, focusing on their association with hormone levels and other clinical parameters. In this case-control study, fecal samples were collected from women of reproductive age, both with and without PCOS. The analysis of gut β-glucuronidase and β-glucosidase enzymes was conducted with the other clinical parameters, including body mass index, hormone levels, and hirsutism. These factors were then subjected to correlation analysis. PCOS women showed significantly higher levels of β-glucuronidase activity with a statistically significant P-value (0.05 ± 0.1 vs. 0.04 ± 0.1; P = 0.006) as well as β-glucosidase activity (0.13 ± 0.08 vs. 0.09 ± 0.05; P = 0.06) compared to the controls. This study also revealed intriguing connections between the selected enzymes and hormone levels, particularly testosterone and estradiol. Gut microbial enzymes β-glucuronidase and β-glucosidase may be used as biomarkers for early detection and monitoring of PCOS in women with metabolic challenges. It could lead to improved diagnostic tools and treatment options.

Amyotrophic lateral sclerosis (ALS) is a dreadful, devastating and incurable motor neuron disease. Aetiologically, it is a multigenic, multifactorial and multiorgan disease. Despite intense research, ALS pathology remains unexplained. Following extensive literature review, this paper posits a new integrative explanation. This framework proposes that ammonia neurotoxicity is a main player in ALS pathogenesis. According to this explanation, a combination of impaired ammonia removal— mainly because of impaired hepatic urea cycle dysfunction—and increased ammoniagenesis— mainly because of impaired glycolytic metabolism in fast twitch skeletal muscle—causes chronic hyperammonia in ALS. In the absence of neuroprotective calcium binding proteins (calbindin, calreticulin and parvalbumin), elevated ammonia—a neurotoxin—damages motor neurons. Ammonia-induced motor neuron damage occurs through multiple mechanisms such as macroautophagy-endolysosomal impairment, endoplasmic reticulum (ER) stress, CDK5 activation, oxidative/nitrosative stress, neuronal hyperexcitability and neuroinflammation. Furthermore, the regional pattern of calcium binding proteins’ loss, owing to either ER stress and/or impaired oxidative metabolism, determines clinical variability of ALS. Most importantly, this new framework can be generalised to explain other neurodegenerative disorders such as Huntington’s disease and Parkinsonism.

Endometrial cancer (EC), endometriosis (ENDO), and obesity (OBY) are interconnected conditions in women that may share underlying genetic pathways. This study aimed to identify shared genetic pathways and differential gene expressions across these conditions to uncover potential therapeutic targets. A bioinformatics pipeline was applied using gene expression datasets from the GEO database, incorporating differential expression analysis, functional and pathway enrichment, PPI network construction, survival analysis, and mutational profiling across 198 samples. The analysis revealed 26 shared differentially expressed genes (DEGs), with IGF-1, CREBBP, EP300, and PIAS1 identified as key hub genes. Elevated IGF-1 expression was significantly linked to poorer survival outcomes in EC patients (p < .05). Frequent mutations were observed in these hub genes, suggesting their critical role in disease mechanisms. This study highlights genetic links among EC, ENDO, and OBY, emphasizing high IGF-1 expression as a potential prognostic marker in EC and recurrent alterations in hub genes as promising therapeutic targets. These findings provide insights into the shared genetic underpinnings of these conditions and present new avenues for targeted therapies.

Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder characterized by hormonal imbalances and metabolic dysregulation. Emerging evidence sugg