Dysbiosis of the Human Urinary Microbiome and its Association to Diseases Affecting the Urinary System.

The human urinary microbiome, also termed urobiome, has been overlooked due to the clinical dogma of sterile urine, as reported by routine culture. However, evolving sensitive tools such as expanded quantitative urine culture, 16S ribosomal RNA gene sequencing, and next-generation sequencing have discovered a vast number of microorganisms present in urine, even in healthy individuals. Microbiome dysbiosis and its links to disease is a heavily explored area in several microbial niches. Presently, urobiome dysbiosis and its correlation to urinary system-related diseases is at its infancy but rapidly emerging, as it provides potential therapeutic insights. This review outlines the changes in the human urinary microbiome concerning globally prevalent diseases affecting kidney function, such as chronic kidney disease (CKD), diabetes mellitus (DM), hypertension (HT), and urinary tract infection (UTI). Alterations to urine microbial diversity, including differences in the abundance and species richness of particular microbial genera, notably Lactobacillus, Prevotella, Streptococcus, Staphylococcus, Klebsiella, Enterococcus, between diseased and healthy samples are discussed utilising studies to date. Subsequent research needs to move beyond correlation to understand the roles of the urinary microbiota in diseases, thereby clarifying whether urinary dysbiosis has causal contributions that may provide important insight for diagnostics, pathophysiology, and therapy in renal pathologies.

Prelimbic Cortical Stimulation Induces Antidepressant-like Responses through Dopaminergic-Dependent and -Independent Mechanisms.

High-frequency stimulation (HFS) is a promising therapy for patients with depression. However, the mechanisms underlying the HFS-induced antidepressant-like effects on susceptibility and resilience to depressive-like behaviors remain obscure. Given that dopaminergic neurotransmission has been found to be disrupted in depression, we investigated the dopamine(DA)-dependent mechanism of the antidepressant-like effects of HFS of the prelimbic cortex (HFS PrL). We performed HFS PrL in a rat model of mild chronic unpredictable stress (CUS) together with 6-hydroxydopamine lesioning in the dorsal raphe nucleus (DRN) and ventral tegmental area (VTA). Animals were assessed for anxiety, anhedonia, and behavioral despair. We also examined levels of corticosterone, hippocampal neurotransmitters, neuroplasticity-related proteins, and morphological changes in dopaminergic neurons. We found 54.3% of CUS animals exhibited decreased sucrose consumption and were designated as CUS-susceptible, while the others were designated CUS-resilient. HFS PrL in both the CUS-susceptible and CUS-resilient animals significantly increased hedonia, reduced anxiety, decreased forced swim immobility, enhanced hippocampal DA and serotonin levels, and reduced corticosterone levels when compared with the respective sham groups. The hedonic-like effects were abolished in both DRN- and VTA-lesioned groups, suggesting the effects of HFS PrL are DA-dependent. Interestingly, VTA-lesioned sham animals had increased anxiety and forced swim immobility, which was reversed by HFS PrL. The VTA-lesioned HFS PrL animals also had elevated DA levels, and reduced p-p38 MAPK and NF-κB levels when compared to VTA-lesioned sham animals. These findings suggest that HFS PrL in stressed animals leads to profound antidepressant-like responses possibly through both DA-dependent and -independent mechanisms.