Biology subjects

Munyoki, S. K.

Publications and source records attributed to Munyoki, S. K..

4 recordsLinked to original sources

bioRxiv2024

The microbiota extends the reproductive lifespan by safeguarding the ovarian reserve

Infertility is a devastating condition affecting one in six people globally. In many cases, the underlying causes are unknown. Emerging evidence suggests that the microbiota influences reproduction, yet the mechanistic link between the microbiota, ovarian function, and length of the fertile lifespan remain unexplored. Here we report that the microbiota controls the length of the reproductive lifespan by maintaining the primordial follicle pool, a process mediated by microbiota-derived short chain fatty acids modulating gene regulatory networks crucial for the survival of the ovarian reserve. Dietary perturbation of the microbiota during a critical developmental window is sufficient to diminish the ovarian reserve, reduce oocyte retrieval, and impair preimplantation embryo viability, mirroring challenges in human fertility treatments. Targeted interventions to restore microbiota improve assisted reproductive outcomes, particularly when implemented early. These findings reveal a novel contribution of host-microbe interactions in mammalian reproduction and demonstrate that the microbiota impacts ovarian function and fertility.

developmental biology↗

bioRxiv2023

Diet influences community dynamics following vaginal group B Streptococcus colonization

The vaginal microbiota plays a pivotal role in reproductive, sexual, and perinatal health and disease. Unlike the well-established connections between diet, metabolism, and the intestinal microbiota, parallel mechanisms influencing the vaginal microbiota and pathogen colonization remain overlooked. In this study, we combine a mouse model of Streptococcus agalactiae strain COH1 (GBS) vaginal colonization with a mouse model of pubertal-onset obesity to assess diet as a determinant of vaginal microbiota composition and its role in colonization resistance. We leveraged culture-dependent assessment of GBS clearance and culture-independent, sequencing-based reconstruction of the vaginal microbiota in relation to diet, obesity, glucose tolerance, and microbial dynamics across time scales. Our findings demonstrate that excessive body weight gain and glucose intolerance are not associated with vaginal GBS density or timing of clearance. Diets high in fat and low in soluble fiber are associated with vaginal GBS persistence, and changes in vaginal microbiota structure and composition due to diet contribute to GBS clearance patterns in nonpregnant mice. These findings underscore a critical need for studies on diet as a key determinant of vaginal microbiota composition and its relevance to reproductive and perinatal outcomes. IMPORTANCEThis work sheds light on diet as a key determinant influencing the composition of vaginal microbiota and its involvement in group B Streptococcus (GBS) colonization in a mouse model. The study shows that dietary components, such as dietary fat and soluble fiber, impact GBS density and timing of clearance in the female reproductive tract. These findings are particularly significant given clear links between GBS and adverse reproductive and neonatal outcomes, advancing our understanding by identifying critical connections between dietary components, factors originating from the intestinal tract, vaginal microbiota, and reproductive outcomes.

microbiology↗

bioRxiv2022

The magnitude of sex differences in host-microbe interactions are time-of-day dependent

Circadian rhythms dynamically regulate sex differences in metabolism and immunity, and circadian disruption increases the risk of metabolic disorders. We investigated the role of sex-specific microbial circadian rhythms in host metabolism using germ-free and conventionalized female and male mice, dietary manipulations, coupled with a systems biology approach. Sex differences in circadian rhythms of genes involved in immunity and metabolism are dependent on oscillations in the microbiota, microbial metabolic functions, and microbial metabolites. Further, dietary factors modify the magnitude of sex differences in host-microbe circadian dynamics. We show that consuming an obesogenic high-fat, low-fiber diet produced sex-specific changes in circadian rhythms in microbiota, metabolites, and host gene expression, which were linked to sex differences in the severity of metabolic dysfunction. These results reveal that microbial circadian rhythms contribute to sex differences in metabolism, emphasizing the need to consider sex as a biological variable in research on microbial contributions to metabolic dysfunction. HIGHLIGHTSO_LIMicrobial circadian rhythms differ by sex. C_LIO_LISex-specific rhythms in host transcriptional networks are microbiome-dependent. C_LIO_LIDiet-induced obesity entrains new sex-specific rhythms in microbiome and host genes. C_LIO_LITiming of data collection influences magnitude of sex differences. C_LI

systems biology↗

bioRxiv2021

Single-Cell Analysis of Human Testis Aging, and Impact of Elevated Body Mass Index

Aging human males display reduced reproductive health, however testis aging is poorly understood at the molecular and genomic level. Here, we utilized single-cell RNA-seq to profile over 44,000 cells from both young and older men (>60 years old) - and examined age-related changes in germline development and in the somatic niche. Interestingly, age-related changes in spermatogonial stem cells appeared modest, whereas age-related dysregulation of spermatogenesis and the somatic niche ranged from moderate to severe. Altered pathways included signaling and inflammation in multiple cell types, metabolic signaling in Sertoli cells, hedgehog signaling and testosterone production in Leydig cells, cell death and growth in testicular peritubular cells, and possible developmental regression in both Leydig and peritubular cells. Remarkably, the extent of dysregulation correlated with body mass index in older, but not younger men. Taken together, we reveal candidate molecular mechanisms underlying the complex testicular changes conferred by aging, and their exacerbation by concurrent chronic conditions such as obesity.

developmental biology↗