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Publications
Publications (244)
The development of anxiety during protracted opioid withdrawal heightens the risk of relapse into the cycle of addiction. Understanding the mechanisms driving anxiety during opioid withdrawal could facilitate the development of therapeutics to prevent negative affect and promote continued abstinence. Our lab has previously established the gut micro...
Microglia are a key cell type in the central nervous system that play a role in a plethora of functions throughout development, in homeostasis, and in disease states. As the resident immune cells of the developed brain, microglia survey their environment for threats to the CNS and induce a cytokine and chemokine response to resolve the pathological...
IgA binding dictates the composition of the intestinal microbiome and reflects dysbiotic states during chronic disease. Both pathogenic and commensal bacteria differentially bind to IgA with varying outcomes. Little is known regarding IgA dynamics immediately following microbial dysbiosis. Recent work shows that morphine treatment rapidly induces m...
Millions of people suffer from opioid use disorder, because of the ongoing opioid epidemic. The aversive symptoms of withdrawal are a leading factor for drug relapses, yet there are limited therapeutic options to minimize or prevent withdrawal symptoms. The mechanism behind opioid withdrawal is still not fully understood, thus preventing the develo...
BACKGROUND
Clinical data demonstrate that chronic use of opioid analgesics increases neuropathic pain in people living with human immunodeficiency virus (HIV). Therefore, it is important to elucidate the molecular mechanisms of HIV-related chronic pain. In this study, we investigated the role of the transcription factor cMyc, epigenetic writer enha...
Opioids, such as morphine and oxycodone, are widely used for pain management associated with chronic pancreatitis (CP); however, their impact on the progression and pain sensitivity of CP has never been evaluated. This report investigates the impact of opioid use on the severity of CP, pain sensitivity, and the gut microbiome. C57BL/6 mice were div...
Distal Sensory Peripheral Neuropathy (DSP) is a common complication in HIV-infected individuals, leading to chronic pain and reduced quality of life. Even with antiretroviral therapy (ART), DSP persists, often prompting the use of opioid analgesics, which can paradoxically worsen symptoms through opioid-induced microbial dysbiosis. This study emplo...
There has been a rapid increase in neonates born with a history of prenatal opioid exposure. How prenatal opioid exposure affects pain sensitivity in offspring is of interest, as this may perpetuate the opioid epidemic. While few studies have reported hypersensitivity to thermal pain, potential mechanisms have not been described. This study posits...
Distal Sensory Peripheral Neuropathy (DSP) is a common complication in HIV-infected individ-uals, leading to chronic pain and reduced quality of life. Despite antiretroviral therapy (ART), DSP persists, often prompting the use of opioid analgesics, which can paradoxically worsen symptoms through opioid-induced microbial dysbiosis. This study employ...
TET methylcytosine dioxygenase 2 ( TET2) loss-of-function mutations induce a pre-malignant state known as clonal hematopoiesis of indeterminate potential (CHIP). CHIP occurs in approximately 10% of people over 65 years of age and confers a 10-fold greater risk of developing hematological malignancy. Several environmental factors, including radiatio...
The cycle of substance use disorder (SUD) leading to dependence is a complex process involving multiple neurocircuitries and brain regions. The amygdala is the core brain region that is involved in processing withdrawal and anxiety and depressive-like behaviors. However, the transcriptional changes in each cell type within the amygdala during SUD r...
Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for recurrent Clostridioides difficile infection (rCDI) and also a potential therapy for other diseases associated with dysbiotic gut microbiota. Monitoring metabolic changes in biofluids and excreta is a noninvasive approach to identify the biomarkers of microbial rec...
Purpose
The goal of this systematic review was to examine the current literature on the urinary microbiome and its associations with noninfectious, nonmalignant, urologic diseases. Secondarily, we aimed to describe the most common bioinformatics used to analyze the urinary microbiome.
Methods
A comprehensive literature search of Ovid MEDLINE using...
Opioid crisis is an ongoing epidemic since the past several decades in the United States. Opioid use-associated microbial dysbiosis is emerging as a key regulator of intestinal homeostasis and behavioral responses to opioid. However, the mechanistic insight into the role of microbial community in modulating host response is unavailable. To uncover...
The current opioid pandemic is a major public health crisis in the United States, affecting millions of people and imposing significant health and socioeconomic burdens. Preclinical and clinical research over the past few decades has delineated certain molecular mechanisms and identified various genetic, epigenetic, and environmental factors respon...
The 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 strategie...
Objectives:
To study the semen microbiome profile in men with non-obstructive azoospermia (NOA) would differ from that of fertile controls (FC).
Design:
Using quantitative PCR and 16s rRNA, we sequenced semen samples from men with NOA (FSH > 10 IU/mL, testis volume < 10cc) and fertile controls and performed comprehensive taxonomic microbiome ana...
Background and Objective
Opioid use disorder is an evolving crisis, and 17.2% of postsurgical patients continue to fill an opioid prescription one year after surgery. Preclinical studies suggest perioperative opioid use, defined here as opioids used in the setting of operative pain, may be linked to inferior oncologic outcomes. If this were true, o...
TET2 loss-of-function mutations induce a pre-malignant state known as clonal hematopoiesis of indeterminate potential (CHIP). CHIP occurs in approximately 10% of people over 65 years of age and confers a 10-fold greater risk of developing hematological malignancy. Several environmental factors, including radiation, sleep deprivation, atherosclerosi...
Background
The microbiome is essential to immune development, defense against pathogens, and modulation of inflammation. Microbial dysbiosis has been reported in various diseases including human immunodeficiency virus (HIV) and opioid use disorder (OUD). Notably, people living with HIV (PLWH) have been reported to both have higher rates of OUD and...
Morphine administration causes system-level metabolic changes. Here, we show that morphine-tolerant mice exhibited distinct plasma metabolic signatures upon acute and chronic administration. We utilized a mouse model of morphine tolerance by exposing mice to increasing doses of the drug over 4 days. We collected plasma samples from mice undergoing...
Background and Purpose
Opioids are the standard drug for pain management; however, their effects on gastric dysfunction are relatively understudied. Opioid users have a higher incidence of gastric pathology leading to increased hospitalization. Herein, we investigated the consequences of morphine use on gastric pathology and the underlying mechanis...
Background and Purpose
Opioids are commonly used for the management of cancer‐associated pain and chemotherapy‐induced diarrhoea. The chemotherapeutic irinotecan (CPT‐11) causes severe gastrointestinal (GI) toxicity due to deconjugation of inactive metabolite SN‐38 glucuronide (SN‐38G) by bacterial β‐glucuronidases to the active 7‐ethyl‐10‐hydroxyc...
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...
Over 37 million people worldwide are living with HIV. Although the availability of antiretroviral therapy has significantly reduced the number of AIDS-related deaths, individuals living with HIV are at increased risk for opportunistic infections.
The gut microbial ecosystem exhibits a complex bidirectional communication with the host and is one of the key contributing factors in determining mucosal immune homeostasis or an inflammatory state. Opioid use has been established to induce gut microbial dysbiosis consistent with increased intestinal tissue inflammation. In this study, we investig...
Despite the many advancements in the field of pain management, the use of intravenous opioids, such as morphine, in neonates is still a challenge for clinicians and researchers, as the available evidence concerning the long-term consequences of such an early exposure is limited. In particular, little is known concerning the long-term consequences o...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an imminent threat to human health and public safety. ACE2 and transmembrane serine protease 2 proteins on host cells provide the viral entry point to SARS-CoV-2. Although SARS-CoV-2 mainly infects the respiratory system, there have been reports of viral neurotropism and central nervou...
This study characterized compositional and functional shifts in the intestinal and oral microbiome in HIV-positive patients compared to uninfected individuals. 79 specimens were collected from 5 HIV-positive and 12 control subjects from five locations (colon brush, colon wash, TI brush, TI wash and saliva) during colonoscopy and at patient visits....
Introduction:
During the first year of the COVID-19 pandemic, over 93,000 Americans lost their lives to a preventable overdose. Medications for opioid use disorder (OUD) have been shown to decrease mortality in OUD but are underutilized. Through this case-based learning exercise, first-year medical students applied physiologic and pharmacologic pr...
Opioids are the gold standard for chronic and acute pain management however its consequence on gastric function is relatively understudied. Opioid users have a higher incidence of gastric dysfunction, worse quality of life, increased hospitalizations, and increased use of antiemetic and pain modulator medications. In the current study, we show that...
Substance use disorder (SUD) is a prevalent disease that has caused hundreds of thousands of deaths and affected the lives of even more. Despite its global impact, there is still no known cure for SUD, or the psychological symptoms associated with drug use. Many of the behavioral consequences of drug use prevent people from breaking the cycle of ad...
Substance use disorder (SUD) is a complex process in which several neurocircuits are disturbed and various brain regions are involved. The amygdala is a region that mediates the withdrawal effect as well as anxiety and depression-like behaviors. However, the specific transcriptional changes in each cell type during SUD is largely unknown. Here we p...
Sepsis has recently been defined as life-threatening organ dysfunction caused by the dysregulated host response to an ongoing or suspected infection. To date, sepsis continues to be a leading cause of morbidity and mortality amongst hospitalized patients. Many risk factors contribute to development of sepsis, including pain-relieving drugs like opi...
Opioid use disorder (OUD) is defined as the chronic use or misuse of prescribed or illicitly obtained opioids and is characterized by clinically significant impairment. The etiology of OUD is multifactorial as it is influenced by genetics, environmental factors, stress response and behavior. Given the profound role of the gut microbiome in health a...
Background
Chronic pancreatitis (CP) is an inflammatory disease of the pancreas with loss of exocrine/endocrine functions as well as development of fibrosis. Dysbiosis of gut microbiome has been shown to be involved in the pathogenesis of many disease processes. Therefore, we aim to investigate the alteration in gut microbiome associated with CP in...
Prenatal opioid exposure is associated with significantly adverse medical, developmental, and behavioral outcomes in offspring, though the underlying mechanisms driving these impairments are still unclear. Accumulating evidence implicates gut microbial dysbiosis as a potential modulator of these adverse effects. However, how opioid exposure during...
Vaccines offer a promising prophylactic and therapeutic intervention to counteract opioid use disorders (OUD) and fatal overdoses. Vaccines generate opioid-specific antibodies that bind the target opioid, reducing drug distribution to the brain and preventing drug-induced behavioral and pharmacological effects. Due to their selectivity, anti-opioid...
HIV trans-activator of transcription (Tat), one of the cytotoxic proteins secreted from HIV-infected cells, is also known to facilitate chemokine-mediated transmigration of monocytes into the brain leading, in turn, to neuroinflammation and thereby contributing to the development of HIV-associated neurocognitive disorders (HAND). The mechanism(s) u...
HPV-induced cervical cancer is one of the prevalent gynecological cancers world-wide. In the present study, we determined the efficacy of Minnelide, a prodrug which is converted to its active form (Triptolide) in vivo against cervical cancer cells. Our studies show that Triptolide inhibited HPV-16 and HPV-18 positive cells at nanomolar concentratio...
Extracellular vesicles (EVs) are effective mediators of intercellular communications between enterocytes and immune cells. The current study showed that EVs isolated from mouse and human intestinal organoids modulated inflammatory responses of various immune cells including mouse bone-marrow derived-macrophages, dendritic cells, microglia cells, an...
Chronic exposure to opioids typically results in adverse consequences. Opioid use disorder (OUD) is a disease of the CNS with behavioral, psychological, neurobiological, and medical manifestations. OUD induces a variety of changes of neurotransmitters/neuropeptides in the nervous system. Existing pharmacotherapy, such as opioid maintenance therapy...
The heightened incidence of opioid use during pregnancy has resulted in unprecedented rates of neonates prenatally exposed to opioids. Prenatal opioid exposure (POE) results in significantly adverse medical, developmental, and behavioral outcomes in offspring. Of growing interest is whether POE contributes to future vulnerability to substance use d...
Background
Gut microbiota may impact cognitive function and decline, though data are limited. This pilot study examines the associations between gut dysbiosis products, plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14), with cognitive decline and immune molecule activation among 40 participants in the longitudinal population-based Northern M...
Background and Purpose
A significant number of HIV‐1 patients on antiretroviral therapy develop HIV‐associated neurocognitive disorders (HAND). Evidence indicate that biological sex may regulate HAND pathogenesis, but the mechanisms remain unknown. We investigated synaptic mechanisms associated with sex differences in HAND, using the HIV‐1‐transgen...
Background
Gut microbiota may impact cognitive function and decline, though data is limited. This pilot study examines the associations between gut dysbiosis products, plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14), with cognitive decline and immune molecule activation among 40 participants in the longitudinal population-based Northern Ma...
Growing evidence from animal and human studies show that opioids have a major impact on the composition and function of gut microbiota. This leads to disruption in gut permeability and altered microbial metabolites, driving both systemic and neuroinflammation, which in turn impacts central nervous system (CNS) homeostasis. Tolerance and dependence...
The stimulator of interferon genes (STING) pathway has been proposed as a key regulator of gastrointestinal homeostasis and inflammatory responses. Although STING reportedly protects against gut barrier damage and graft-versus-host disease (GVHD) after major histocompatibility complex (MHC)–mismatched allogeneic hematopoietic stem cell transplantat...
Graft-versus-host disease (GVHD) remains a significant cause of morbidity and mortality in patients receiving allogeneic hematopoietic stem cell transplants (aHSCTs). Pre-HSCT chemoradiation results in the death of dividing cells and release of endogenous danger signals. These molecules drive the activation of antigen presenting cells (APCs) and th...
Chronic pain is long-lasting nociceptive state, impairing the patient's quality of life. Existing analgesics are generally not effective in the treatment of chronic pain, some of which such as opioids have the risk of tolerance/dependence, overdose death with higher daily opioid doses for increasing analgesic effect. Opioid use disorders have alrea...
Intestinal barrier dysfunction and subsequent microbial translocation play crucial roles in persistent immune activation leading to HIV disease progression. Opioid use is associated with worse outcome in HIV-infected patients. The exacerbated disease progression by opioids is mainly driven by excessive intestinal inflammation and increased gut perm...
Background
Ulcerative colitis (UC) is a Th2 inflammatory bowel disease characterized by increased IL-5 and IL-13 expression, eosinophilic/neutrophilic infiltration, decreased mucus production, impaired epithelial barrier, and bacterial dysbiosis of the colon. Acetylcholine and nicotine stimulate mucus production and suppress Th2 inflammation throug...
Background and aims:
Opioids are the most prescribed analgesics for pain in Inflammatory Bowel Diseases (IBD), however the consequences of opioid use on IBD severity is not well defined. This is the first study investigating consequences of hydromorphone in both dextran sodium sulfate (DSS)-induced colitis and spontaneous colitis [IL-10 knockout (...
Graft-versus-host disease (GVHD) remains a significant cause of morbidity and mortality in patients receiving allogeneic hematopoietic stem cell transplants (aHSCTs). Pre-HSCT conditioning typically consists of irradiation and drug administration resulting in the death of rapidly dividing cells and release of endogenous danger signals. These molecu...
Objectives: After 14 years of no change, new blood pressure (BP) guidelines were released; yet, the impact of marijuana on BP remains unclear. Our objective was to examine the association between marijuana use and BP. Methods: We analyzed data for adults (N = 10,709; mean age 44.8 years; 50.3% men) who completed 2005-2014 National Health and Nutrit...
Cocaine use disorder (CUD), a major health crisis, has traditionally been considered a complication of the CNS; however, it is also closely associated with malnourishment and deteriorating gut health. In light of emerging studies on the potential role of gut microbiota in neurological disorders, we sought to understand the causal association betwee...
Opioid analgesics are frequently prescribed in the United States and worldwide. However, serious side effects such as addiction, immunosuppression and gastrointestinal symptoms limit their use. It was recently demonstrated that morphine treatment results in a significant disruption in gut barrier function, leading to an increased translocation of g...
Background: Recent reports have elaborated on how the gut microbiota shape vertebrate immune system during ontogeny. Additionally, tumor-promoting inflammation and gut dysbiosis are often associated with multiple cancers including pancreatic ductal adenocarcinoma (PDAC). We sought to investigate the gut microbiota-immune relationship in mouse model...
Background: Recent reports have elaborated on how the gut microbiota shape vertebrate immune system during ontogeny. Additionally, tumor-promoting inflammation and gut dysbiosis are often associated with multiple cancers including pancreatic ductal adenocarcinoma (PDAC). We sought to investigate the gut microbiota-immune relationship in mouse model...
Prolonged exposure to opioids results in analgesic tolerance, drug overdose, and death. The mechanism underlying morphine analgesic tolerance still remains unresolved. We show that morphine analgesic tolerance was significantly attenuated in germfree (GF) and in pan-antibiotic−treated mice. Reconstitution of GF mice with naïve fecal microbiota rein...
Human Immunodeficiency Virus (HIV) pathogenesis has been closely linked with microbial translocation, which is believed to drive inflammation and HIV replication. Opioid drugs have been shown to worsen this symptom, leading to a faster progression of HIV infection to Acquired Immunodeficiency Syndrome (AIDS). The interaction of HIV and opioid drugs...
Accumulating evidence shows that extracellular vesicles (EVs) secreted by immune cells play an important role in intercellular communication. In the current report, we show that EVs released from wild-type bone marrow-derived dendritic cells (BMDCs) transfer TLRs to TLR4-knockout (TLR4KO) BMDCs and increase cellular responsiveness to LPS in recipie...