Genetic hypogonadal (Gnrh1hpg) mouse model uncovers influence of reproductive axis on maturation of the gut microbiome during puberty.

The gut microbiome plays a key role in human health and gut dysbiosis is linked to many sex-specific diseases including autoimmune, metabolic, and neurological disorders. Activation of the hypothalamic-pituitary-gonadal (HPG) axis during puberty leads to sexual maturation and development of sex differences through the action of gonadal sex steroids. While the gut microbiome also undergoes sex differentiation, the mechanisms involved remain poorly understood. Using a genetic hypogonadal (hpg) mouse model, we sampled the fecal microbiome of male and female wild-type and hpg mutant mice before and after puberty to determine how microbial taxonomy and function are influenced by age, sex, and the HPG axis. We showed that HPG axis activation during puberty is required for sexual maturation of the gut microbiota composition, community structure, and metabolic functions. We also demonstrated that some sex differences in taxonomic composition and amine metabolism developed independently of the HPG axis, indicating that sex chromosomes are sufficient for certain sex differences in the gut microbiome. In addition, we showed that age, independent of HPG axis activation, led to some aspects of pubertal maturation of the gut microbiota community composition and putative functions. These results have implications for microbiome-based treatments, indicating that sex, hormonal status, and age should be considered when designing microbiome-based therapeutics.

Metals and methylotrophy: Via global gene expression studies.

A number of minerals, such as copper, cobalt, and rare earth elements (REE), are essential modulators of microbial one-carbon metabolism. This chapter provides an overview of the gene expression study design and analysis protocols for uncovering REE-induced changes in methylotrophic bacteria. By interrogating relationships and differences in total gene expression induced by mineral micronutrients, a deeper understanding of gene regulation at a systems scale can be gained. With careful design and execution of RNA-sequencing experiments, thorough processing and assessment of read quality can be utilized to assess and adjust for possible biases. By ensuring only quality data are utilized in downstream processes, differential gene expression, overrepresented analyses, and gene-set enrichment analyses provide reliable and reproducible representation of pathways and functions which are being affected by changes in environmental conditions.