Linking the gut microbiome to microglial activation in opioid use disorder

Substance use disorder (SUD) is a physical and psychological disorder globally prevalent today that has resulted in over 107,000 drug overdose deaths in 2021 in the United States alone. This manuscript reviews the potential relationship between opioid use disorder (OUD), a prevalent subset of SUD, and the microglia, the resident macrophages of the central nervous system (CNS), as they have been found to become significantly more activated during opioid exposure. The inflammatory response mediated by the microglia could contribute to the pathophysiology of SUDs, in particular OUD. Further understanding of the microglia and how they respond to not only signals in the CNS but also signals from other areas of the body, such as the gut microbiome, could explain how the microglia are involved in drug use. Several studies have shown extensive communication between the gut microbiome and the microglia, which may be an important factor in the initiation and development of OUD. Particularly, strategies seeking to manipulate and restore the gut microbiome have been shown to reduce microglial activation and attenuate inflammation. In this review, we discuss the evidence for a link between the microglia and OUD and how the gut microbiome might influence microglial activation to drive the disorder and its associated behaviors. Understanding this connection between microglia and the gut microbiome in the context of drug use may present additional therapeutic targets to treat the different stages of drug use

Linking the gut microbiome to microglial activation in opioid use disorder.

Substance use disorder (SUD) is a physical and psychological disorder globally prevalent today that has resulted in over 107,000 drug overdose deaths in 2021 in the United States alone. This manuscript reviews the potential relationship between opioid use disorder (OUD), a prevalent subset of SUD, and the microglia, the resident macrophages of the central nervous system (CNS), as they have been found to become significantly more activated during opioid exposure. The inflammatory response mediated by the microglia could contribute to the pathophysiology of SUDs, in particular OUD. Further understanding of the microglia and how they respond to not only signals in the CNS but also signals from other areas of the body, such as the gut microbiome, could explain how the microglia are involved in drug use. Several studies have shown extensive communication between the gut microbiome and the microglia, which may be an important factor in the initiation and development of OUD. Particularly, strategies seeking to manipulate and restore the gut microbiome have been shown to reduce microglial activation and attenuate inflammation. In this review, we discuss the evidence for a link between the microglia and OUD and how the gut microbiome might influence microglial activation to drive the disorder and its associated behaviors. Understanding this connection between microglia and the gut microbiome in the context of drug use may present additional therapeutic targets to treat the different stages of drug use

Vasectomy has No Impact on Future Lower Urinary Tract Symptoms Diagnoses: A Retrospective Cohort Claims Database Analysis

The aim of this study was to assess whether there is an association between vasectomy and benign prostatic hyperplasia with associated lower urinary tract symptoms (BPH/LUTS) due to inflammatory etiology. We assessed the incidence of BPH/LUTS in men who had undergone vasectomy in a matched cohort analysis using the TriNetX Research Network. We identified men aged 30 to 60 years who underwent vasectomy and had a follow-up visit within 6 months to 5 years after vasectomy from January 2010 through December 2022 and compared them with matched controls. Outcomes recorded include diagnoses of BPH (N40, N40.1), BPH-related medication prescriptions, and BPH-related procedures. We accounted for confounding variables through propensity score-matching for age; race; and history of comorbid medical conditions: hyperlipidemia (International Classification of Disease-10: E78), metabolic syndrome (E88.81), overweight or obesity (E66), testicular hypofunction (E29.1), hypertension (I10-I16), nicotine dependence (F17), and obstructive sleep apnea (G47.33). There was no significant difference in BPH diagnosis between postvasectomy men vs controls (0.84% vs 0.80%, RR: 0.95, 95% CI 0.86-1.05) or BPH/LUTS diagnosis (0.48% vs 0.44%, RR: 0.92, 95% CI 0.81-1.05) within 6 months to 5 years after vasectomy, respectively. No differences in BPH medication prescription (0.94% vs 0.84%) or rate of BPH procedures (0.022% vs 0.017%) were detected between the 2 groups. This study suggests that vasectomy does not increase the risk of BPH development and/or LUTS worsening compared with the general population, providing assurance to both patients and health care providers who may consider vasectomy as a safe family planning option

Predictive Value of Urodynamic Studies for Overactive Bladder

Purpose of ReviewThe use of urodynamic studies (UDS) in overactive bladder (OAB) diagnosis is contested due to concerns of invasiveness, cost-effectiveness, and relative lack of impact on treatment strategy. We aimed to provide a comprehensive review of the role of UDS in the diagnosis of refractory OAB, while also providing a synthesis of recent studies on this topic.Recent FindingsRecent studies that endorse the use of UDS show that incorporation of UDS findings may increase patient compliance and satisfaction with OAB treatment. Studies suggest that this greater patient satisfaction may be attributed to the ability of UDS to better identify the unique pathophysiology of OAB for each patient. One study found that UDS is also useful in diagnosing comorbid conditions, thereby affording clinicians the ability to individually tailor treatment. However, other studies showed that UDS did not significantly change the diagnosis and management in cases of uncomplicated OAB.SummaryThe use of UDS in the diagnostic algorithm of OAB may depend on the degree of certainty needed by individual providers to make a diagnosis and the extent to which findings would change the course of treatment. Individual patient history, clinical manifestations, and reported symptoms will influence further the appropriateness of UDS in given scenarios. Future studies are needed to better delineate the role of UDS in the assessment and management of refractory OAB

The Impact of Obesity on Sperm Parameters in Young Adult Males: A Retrospective Study of Sperm Donors

OBJECTIVETo utilize a large cohort of healthy sperm bank donors to evaluate the association between body mass index (BMI) and individual sperm parameters. METHODSSperm parameters from donors across the United States were obtained between 2013-2022. Donors were healthy men aged 18-46 years old. Semen samples were analyzed in a certified lab following guidelines by the World Health Organization. A multivariable interaction model between age, BMI, and sperm parameters was conducted. RESULTSThere were 117,357 sperm donations included in our study. In our sample, 98,397 (83.84%) men were classified as young donors (ages 18-32 years) and 18,960 (16.16%) were classified as old donors (ages 33-46 years). We identified 1,032 (0.88%) men as underweight, 76,635 (65.30%) as normal weight, 36,686 (31.26%) as overweight, and 3,004 (2.56%) as obese. Participants had a median Total Motile Sperm Count (TMSC) of 186 (IQR: 128 million), volume of 3.36 (IQR: 1.82mL), sperm concentration of 56 (IQR: 34 million/mL) and a progressive motility of 59.84% (IQR: 16.95%). Older obese donor had lower TMSC (β = -22.98±4.66, p < 0.001), semen volumes (β = -0.85±0.06, p < 0.001), and progressive motility (β = -3.94±0.56, p < 0.001) compared to younger, healthy weight donors. CONCLUSIONSWe observed lower TMSC, semen volumes, and progressive motility in older obese donors. Although these values are within the normal expected ranges for individual sperm parameters, our ability to detect differences even within this healthy population highlights the importance of maintaining a healthy diet and exercise regimen for preserving high sperm counts

The gut microbiome contributes to somatic morphine withdrawal behavior and implicates a TLR2 mediated mechanism

ABSTRACTThe ongoing opioid epidemic has left millions of people suffering from opioid use disorder due to the over-prescription of highly addictive substances. Chronic opioid exposure leads to dependence, where the absence of the drug results in negative symptoms of withdrawal, often driving patients to continue drug use; however, few therapeutic strategies are currently available to combat the cycle of addiction and the severity of morphine withdrawal. This study investigates the microbiome as a potential therapeutic target for morphine withdrawal, as gut dysbiosis caused by morphine use has been proven to contribute to other aspects of opioid use disorders, such as tolerance. Results show that although the microbiome during morphine withdrawal trends toward recovery from morphine-induced dysbiosis, there continues to be a disruption in the alpha and beta diversity as well as the abundance of gram-positive bacteria that may still contribute to the severity of morphine withdrawal symptoms. Germ-free mice lacking the microbiome did not develop somatic withdrawal symptoms, indicating that the microbiome is necessary for the development of somatic withdrawal behavior. Notably, only TLR2 but not TLR4 whole-body knockout models display less withdrawal severity, implicating that the microbiome, through a gram-positive, TLR2 mediated mechanism, drives opioid-induced somatic withdrawal behavior