A Galleria Model of Cryptococcus neoformans Infection.

Galleria mellonella larvae are a popular and simple model organism for infectious disease research. Last instar larvae can be purchased inexpensively from commercial suppliers and infected with Cryptococcus. Injection into the proleg of larvae results in systemic infections. Larvae may then be monitored for survival or homogenized to determine fungal burden. Fixation of infected larvae produces samples suitable for histological staining and analysis.

Modeling type 1 diabetes progression using machine learning and single-cell transcriptomic measurements in human islets.

Type 1 diabetes (T1D) is a chronic condition in which beta cells are destroyed by immune cells. Despite progress in immunotherapies that could delay T1D onset, early detection of autoimmunity remains challenging. Here, we evaluate the utility of machine learning for early prediction of T1D using single-cell analysis of islets. Using gradient-boosting algorithms, we model changes in gene expression of single cells from pancreatic tissues in T1D and non-diabetic organ donors. We assess if mathematical modeling could predict the likelihood of T1D development in non-diabetic autoantibody-positive donors. While most autoantibody-positive donors are predicted to be non-diabetic, select donors with unique gene signatures are classified as T1D. Our strategy also reveals a shared gene signature in distinct T1D-associated models across cell types, suggesting a common effect of the disease on transcriptional outputs of these cells. Our study establishes a precedent for using machine learning in early detection of T1D.

Targeting lipid nanoparticles to the blood-brain barrier to ameliorate acute ischemic stroke.

Effective delivery of mRNA or small molecule drugs to the brain is a significant challenge in developing treatment for acute ischemic stroke (AIS). To address the problem, we have developed targeted nanomedicine to increase drug concentrations in endothelial cells of the blood-brain barrier (BBB) of the injured brain. Inflammation during ischemic stroke causes continuous neuronal death and an increase in the infarct volume. To enable targeted delivery to the inflamed BBB, we conjugated lipid nanocarriers (NCs) with antibodies that bind cell adhesion molecules expressed at the BBB. In the transient middle cerebral artery occlusion mouse model, NCs targeted to vascular cellular adhesion molecule-1 (VCAM) achieved the highest level of brain delivery, nearly two orders of magnitude higher than untargeted ones. VCAM-targeted lipid nanoparticles with luciferase-encoding mRNA and Cre-recombinase showed selective expression in the ischemic brain. Anti-inflammatory drugs administered intravenously after ischemic stroke reduced cerebral infarct volume by 62% (interleukin-10 mRNA) or 35% (dexamethasone) only when they were encapsulated in VCAM-targeted NCs. Thus, VCAM-targeted lipid NCs represent a new platform for strongly concentrating drugs within the compromised BBB of penumbra, thereby ameliorating AIS.

Factors associated with HIV viral load control in the early postpartum period - a Canadian prospective cohort study.

Despite success in managing HIV during pregnancy, challenges remain around sustained adherence with antiretroviral therapy (ART), and the suboptimal viral load (VL) suppression during the postpartum period. The objective of this study was to compare VL levels at delivery and during the postpartum period and assess factors associated with lack of viral suppression during the postpartum period in Canada. We combined data from two Canadian prospective cohorts, which included 286 HIV-positive women (352 pregnancies) who delivered between 2012 and 2020. Delivery VL, postpartum VL, and potential factors associated with an undetectable VL (<50 copies/mL), 2-18 weeks after delivery were assessed. To account for the correlation between multiple pregnancies from the same woman, generalized estimating equations were used to assess bivariate associations. Ninety-nine per cent of pregnant women were on ART during pregnancy compared to 93% during the postpartum period. Of those with available VL results (n = 214 pregnancies), 94% of women achieved an undetectable VL at delivery compared to 87% during the postpartum period. The postpartum period is a challenging time for ART use and VL control. Qualitative studies are needed to better understand these challenges and guide us in designing adequate interventions.

Oil-water interface and emulsion stabilising properties of rapeseed proteins napin and cruciferin studied by nonlinear surface rheology.

HYPOTHESIS: Two major protein families are present in rapeseed, namely cruciferins and napins. The structural differences between the two protein families indicate that they might behave differently when their mixture stabilises oil-water interfaces. Therefore, this work focuses on elucidating the role of both proteins in interface and emulsion stabilisation. EXPERIMENTS: Protein molecular properties were evaluated, using SEC, DSC, CD, and hydrophobicity analysis. The oil-water interface mechanical properties were studied using LAOS and LAOD. General stress decomposition (GSD) was used as a novel method to characterise the nonlinear response. Additionally, to evaluate the emulsifying properties of the rapeseed proteins, emulsions were prepared using pure napins or cruciferin and also their mixtures at 1:3, 1:1 and 3:1 (w:w) ratios. FINDINGS: Cruciferins formed stiff viscoelastic solid-like interfacial layers (Gs' = 0.046 mN/m; Ed' = 30.1 mN/m), while napin formed weaker and more stretchable layers at the oil-water interface (Gs' = 0.010 mN/m; Ed' = 26.4 mN/m). As a result, cruciferin-formed oil droplets with much higher stability against coalescence (coalescence index, CI up to 10%) than napin-stabilised ones (CI up to 146%) during two months of storage. Both proteins have a different role in emulsions produced with napin-cruciferin mixtures, where cruciferin provides high coalescence stability, while napin induces flocculation. Our work showed the role of each rapeseed protein in liquid-liquid multiphase systems.

Rhenium fac-Tricarbonyl Bisimine Chalcogenide Complexes: Synthesis, Photophysical Studies, and Confocal and Time-Resolved Cell Microscopy.

We describe the preparation, characterization, and imaging studies of rhenium carbonyl complexes with a pyta (4-(2-pyridyl)-1,2,3-triazole) or tapy (1-(2-pyridyl)-1,2,3-triazole)-based heteroaromatic N∧N ligand and thiolate or selenoate X ligand. The stability and photophysical properties of the selenolate complexes are compared with parent chloride complexes and previously described analogues with benzenethiolate ligands. Two complexes were imaged in A549 cells upon excitation at 405 nm. Colocalization studies suggest a lysosomal accumulation, while one parent chloride complex was described to localize at the Golgi apparatus. Preliminary fluorescence lifetime measurements and imaging demonstrate potential for application in time-resolved microscopy techniques due to the long and variable lifetimes observed in cellular environments, including an increase in lifetime between the solution and solid state many times larger than previously reported.

Longitudinal Assessment of Bone Mineral Density in Women Living With and Without HIV Across Reproductive Phases.

BACKGROUND: Women living with HIV commonly experience low areal bone mineral density (BMD), but whether this is affected by low ovarian hormonal states (prolonged amenorrhea or menopause) is unknown. We compared rates of BMD loss between women living with HIV and HIV-negative control women and investigated its association with low ovarian hormonal states. SETTING: Women living with HIV were enrolled from Vancouver Canada and controls from 9 Canadian sites. METHODS: This longitudinal analysis included age-matched women living with HIV in the Children and Women: AntiRetrovirals and Markers of Aging cohort and controls in the population-based Canadian Multicentre Osteoporosis Study. Rate of change/year in BMD at the total hip and lumbar spine (L1-L4) between 3 and 5 years was compared between groups, adjusting for sociodemographic and clinical variables. RESULTS: Ninety-two women living with HIV (median [interquartile range] age: 49.5 [41.6-54.1] years and body mass index: 24.1 [20.7-30.8] kg/m 2 ) and 278 controls (age: 49.0 [43.0-55.0] years and body mass index: 25.8 [22.9-30.6] kg/m 2 ) were included. Total hip BMD loss was associated with HIV (ß: -0.003 [95% CI: -0.006 to -0.0001] g/cm 2 /yr), menopause (ß: -0.007 [-0.01 to -0.005] g/cm 2 /yr), and smoking (ß: -0.003 [-0.006 to -0.0002] g/cm 2 /yr); BMD gain was linked with higher body mass index (ß: 0.0002 [0.0007-0.0004] g/cm 2 /yr). Menopause was associated with losing L1-L4 BMD (ß: -0.01 [-0.01 to -0.006] g/cm 2 /yr). Amenorrhea was not associated with BMD loss. CONCLUSIONS: HIV and menopause negatively influenced total hip BMD. These data suggest women living with HIV require hip BMD monitoring as they age.

Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19.

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood. METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models. RESULTS: Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20% lower levels of plasma N-Ag compared with placebo (95% confidence interval, 12%-27%; P < .001), and a steeper rate of decline through the first 5 days (P < .001). The treatment difference did not vary between subgroups, and no difference was observed in trajectories of other biomarkers or the day 5 pulmonary ordinal scale. CONCLUSIONS: Our study suggests that nmAb has an antiviral effect assessed by plasma N-Ag among hospitalized patients with COVID-19, with no blunting of the endogenous anti-nucleocapsid antibody response. No effect on systemic inflammation or day 5 clinical status was observed. CLINICAL TRIALS REGISTRATION: NCT04501978.

Variations in CD4 counts during pregnancy in women living with HIV.

OBJECTIVE: Our objective was to determine the frequency at which CD4 counts drop below 200 cells/mm3 during pregnancy in women living with HIV and to identify factors associated with this. METHODS: Data from 2005 to 2020 from two prospective Canadian cohorts of pregnant women living with HIV were extracted. As per national guidelines, women received antiretroviral therapy and CD4 counts were monitored once per trimester and at delivery. RESULTS: Among 775 included cases, 72 (9.3%) had CD4 counts <200 cells/mm3 at the first pregnancy visit. Of the 703 remaining pregnancies with CD4 counts ≥200 cells/mm3 at the initial visit, 20 (2.8%) were associated with a drop to <200 cells/mm3 . In univariate analysis, factors associated with this drop were coinfection with hepatitis B virus or hepatitis C virus (odds ratio [OR] 4.0, 95% confidence interval [CI] 1.52-10.50), lower first visit CD4 counts (OR 0.165, 95% CI 0.08-0.34), and baseline haemoglobin levels <11 g/dL (OR 2.89, 95% CI 1.04-8.00). In multivariable analysis, only CD4 count at first visit remained independently associated with this drop. A cut-off CD4 count ≤450 cells/mm3 at the first pregnancy visit had a sensitivity of 100% to detect cases of CD4 drop to <200 cells/mm3 . CONCLUSION: A drop of CD4 count to <200 cells/mm3 is uncommon during pregnancy in women living with HIV. Our results suggest that CD4 monitoring only once in pregnancy would be safe in women whose CD4 count is >450 cells/mm3 at the first pregnancy visit.

Serotonin reduction in post-acute sequelae of viral infection.

Post-acute sequelae of COVID-19 (PASC, "Long COVID") pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction. Here, we propose a mechanism that links all four hypotheses in a single pathway and provides actionable insights for therapeutic interventions. We find that PASC are associated with serotonin reduction. Viral infection and type I interferon-driven inflammation reduce serotonin through three mechanisms: diminished intestinal absorption of the serotonin precursor tryptophan; platelet hyperactivation and thrombocytopenia, which impacts serotonin storage; and enhanced MAO-mediated serotonin turnover. Peripheral serotonin reduction, in turn, impedes the activity of the vagus nerve and thereby impairs hippocampal responses and memory. These findings provide a possible explanation for neurocognitive symptoms associated with viral persistence in Long COVID, which may extend to other post-viral syndromes.

A subpopulation of lipogenic brown adipocytes drives thermogenic memory.

Sustained responses to transient environmental stimuli are important for survival. The mechanisms underlying long-term adaptations to temporary shifts in abiotic factors remain incompletely understood. Here, we find that transient cold exposure leads to sustained transcriptional and metabolic adaptations in brown adipose tissue, which improve thermogenic responses to secondary cold encounter. Primary thermogenic challenge triggers the delayed induction of a lipid biosynthesis programme even after cessation of the original stimulus, which protects from subsequent exposures. Single-nucleus RNA sequencing and spatial transcriptomics reveal that this response is driven by a lipogenic subpopulation of brown adipocytes localized along the perimeter of Ucp1hi adipocytes. This lipogenic programme is associated with the production of acylcarnitines, and supplementation of acylcarnitines is sufficient to recapitulate improved secondary cold responses. Overall, our data highlight the importance of heterogenous brown adipocyte populations for 'thermogenic memory', which may have therapeutic implications for leveraging short-term thermogenesis to counteract obesity.

NONO::TFE3 fusion cutaneous epithelioid and spindle cell tumor: A case series.

The NONO::TFE3 fusion has been described in MiT family translocation renal cell carcinomas as well as extracutaneous perivascular epithelioid cell tumors (PEComas). PEComas are known to express myogenic and melanocytic markers but SOX10 and p63 positivity has never been reported. We report two primary cutaneous tumors that morphologically and molecularly fit PEComas, both harboring the NONO::TFE3 fusion, but with an unusual immunophenotype of SOX10 and p63 positivity. One case was on an 80-year-old male's finger, and the other one was on a 72-year-old female's thigh. Both were well-circumscribed multinodular dermal tumors composed of nests of monotonous epithelioid to spindled cells with pale to vacuolated cytoplasm, some of which were arranged around blood vessels. Both tumors were positive for SOX10, S100, and p63, focally positive for Melan-A, and negative for myogenic markers. There are very little data regarding the molecular findings of primary cutaneous PEComas. While the NONO::TFE3 fusion has been identified in extracutaneous PEComas, it has never been reported in primary cutaneous cases. We believe these cases represent a previously undescribed subtype of cutaneous tumor which shows some immunophenotypic expression of melanocytic markers and we named these cases NONO::TFE3 fusion cutaneous epithelioid and spindle cell tumor. Further, we raise the question of whether this tumor should fall under the rubric of PEComa because of its morphology, partial expression of melanocytic markers, and the presence of the NONO::TFE3 fusion, or whether these tumors represent a separate novel class of tumors since the immunophenotypic expression of SOX10 and p63 is unusual for PEComas.

Sarcoidal Granuloma Annulare-Like Dermatitis and Vasculitis With Granulomatous Features: An Atypical Case of Giant Cell Arteritis.

ABSTRACT: Giant cell arteritis (GCA) is a diagnosis that clinicians should not miss because of the accompanying risk of irreversible vision loss. GCA can present without the classic symptoms of headache and temporal artery tenderness, which may lead to a delay in diagnosis. Cutaneous findings, although rare, have been associated with GCA. Accordingly, it is imperative to be aware of the broad clinical and histological presentations of GCA, including the cutaneous findings, because they may prove to be harbingers of impending disease. We present a unique case of GCA where 2 distinct cutaneous morphologies, sarcoidal granuloma annulare-like dermatitis and leukocytoclastic vasculitis with granulomatous features, presented simultaneously before the classic symptoms of headache and unilateral vision loss.

Long-Term Change in Bone Mineral Density in Women Living With HIV: A 10-Year Prospective Controlled Cohort Study.

Women living with HIV (WLWH) may be at higher risk for osteoporosis and fragility fractures. However, limited prospective data describe long-term trajectories of bone mineral density (BMD) in WLWH versus women without HIV. Thus, in this prospective study, we aimed to compare 10-year change in areal BMD (aBMD) between WLWH (n = 49; 36.8 ± 8.8 years; 96% pre/perimenopausal) and HIV-negative women (population-based controls; n = 49; 41.9 ± 9.2 years; 80% pre/perimenopausal). In an exploratory analysis, we compared fracture history between WLWH and controls. Outcomes were lumbar spine (L1 to L4), total hip, and femoral neck aBMD at baseline and follow-up, which occurred at 13 and 10 years in WLWH and controls, respectively. We fit multivariable regression models to compare baseline and 10-year change in aBMD between groups, adjusting for osteoporosis risk factors. Within WLWH, we examined associations between aBMD and HIV-related factors, including combination antiretroviral therapy (cART) duration. WLWH were diagnosed 6.5 ± 3.7 years before baseline, 80% were on cART for 241 ± 142 weeks, and 49% had HIV plasma viral load <40 copies/mL. Before and after adjusting for osteoporosis risk factors, baseline and 10-year change in aBMD did not differ between WLWH and controls at any site. At baseline, more WLWH than controls reported a history of low-trauma fracture (30% versus 10%, p < 0.05) and major osteoporotic fracture (17% versus 4%, p < 0.05). During follow-up, the number of WLWH and controls with incident fragility fracture was not significantly different. Lifetime cART duration and tenofovir use were not associated with aBMD 10-year percent change. Higher CD4 count at baseline was positively associated with femoral neck aBMD 10-year percent change. Long-term aBMD change in this small WLWH cohort paralleled normal aging, with no evidence of influence from cART use; however, these results should be interpreted with caution given the small sample size. Larger cohort studies are needed to confirm these findings. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Global Prevalence of Chronic Pain in Women with HIV: A Systematic Review and Meta-analysis.

Chronic pain is common among people with human immunodeficiency virus (HIV) and detrimental to quality of life and overall health. It is often underdiagnosed, undertreated, and frankly dismissed in women with HIV, despite growing evidence that it is highly prevalent in this population. Thus, we conducted a systematic review and meta-analysis to estimate the global prevalence of chronic pain in women with HIV. The full protocol can be found on PROSPERO (identifier CRD42022301145). Of the 2984 references identified in our search, 36 were included in the systematic review and 35 in the meta-analysis. The prevalence of chronic pain was 31.2% (95% confidence interval [CI], 24.6%-38.7%; I2 = 98% [95% CI, 97%-99%]; P < .0001). In this global assessment, we found a high prevalence of chronic pain among women with HIV, underscoring the importance of understanding the etiology of chronic pain, identifying effective treatments, and conducting regular assessments in clinical practice.

Timely Diagnosis of Incubating Syphilis Infections Using Treponema pallidum Transcription-Mediated Amplification Assay.

BACKGROUND: Syphilis is a complex, multistage, sexually transmitted infection (STI) caused by the bacterium Treponema pallidum subspecies pallidum (TP). New diagnostic tools are needed to minimize transmission. In this study, we aimed to assess the additional value of an investigational transcription-mediated amplification test for TP (TP-TMA) for routine diagnostics. METHODS: Between September 2021 and August 2022, visits by all participants of the national preexposure prophylaxis (PrEP) program at the sexual health center (SHC) in Amsterdam were included. Anal, pharyngeal, vaginal, and urine samples collected for Chlamydia trachomatis and Neisseria gonorrhoeae screening were additionally tested with the TP-TMA assay based on detection of 23S rRNA of TP. RESULTS: In total, 9974 SHC visits by 3283 participants were included. There were 191 infectious syphilis cases diagnosed: 26 (14%) primary syphilis, 54 (29%) secondary syphilis, and 111 (58%) early latent syphilis. In 79 of the 191 (41%) syphilis cases, at least 1 sample was TP-TMA-positive. For 16 participants, the positive TP-TMA result was not concordant with routine diagnostics. Of those, 2 participants were treated for syphilis within a week before the visit. Eight participants were treated for a syphilis notification at the visit or for another STI. Five participants were diagnosed with syphilis at the following visit, and 1 participant was lost to follow-up. CONCLUSIONS: By adding the TP-TMA assay to routine diagnostics, we identified 14 of 191 (7%) additional syphilis infections among participants of the national PrEP program. The TP-TMA assay is a useful diagnostic tool to increase syphilis case finding and thus limit the transmission of syphilis.

Targeting lipid nanoparticles to the blood brain barrier to ameliorate acute ischemic stroke.

After more than 100 failed drug trials for acute ischemic stroke (AIS), one of the most commonly cited reasons for the failure has been that drugs achieve very low concentrations in the at-risk penumbra. To address this problem, here we employ nanotechnology to significantly enhance drug concentration in the penumbra's blood-brain barrier (BBB), whose increased permeability in AIS has long been hypothesized to kill neurons by exposing them to toxic plasma proteins. To devise drug-loaded nanocarriers targeted to the BBB, we conjugated them with antibodies that bind to various cell adhesion molecules on the BBB endothelium. In the transient middle cerebral artery occlusion (tMCAO) mouse model, nanocarriers targeted with VCAM antibodies achieved the highest level of brain delivery, nearly 2 orders of magnitude higher than untargeted ones. VCAM-targeted lipid nanoparticles loaded with either a small molecule drug (dexamethasone) or mRNA (encoding IL-10) reduced cerebral infarct volume by 35% or 73%, respectively, and both significantly lowered mortality rates. In contrast, the drugs delivered without the nanocarriers had no effect on AIS outcomes. Thus, VCAM-targeted lipid nanoparticles represent a new platform for strongly concentrating drugs within the compromised BBB of penumbra, thereby ameliorating AIS. Graphical abstract: Acute ischemic stroke induces upregulation of VCAM. We specifically targeted upregulated VCAM in the injured region of the brain with drug- or mRNA-loaded targeted nanocarriers. Nanocarriers targeted with VCAM antibodies achieved the highest brain delivery, nearly orders of magnitude higher than untargeted ones. VCAM-targeted nanocarriers loaded with dexamethasone and mRNA encoding IL-10 reduced infarct volume by 35% and 73%, respectively, and improved survival rates.

Robust tobacco smoking self-report in two cohorts: pregnant women or men and women living with or without HIV.

Understanding the true burden of tobacco smoking on adverse pregnancy outcomes is critical in generating appropriate interventions to improve outcomes. Self-reporting of human behaviour that is associated with stigma is associated with underreporting in general and may bias the impact of smoking in studies; however, self-reporting is frequently the most practical method of gleaning this information. The objective of this study was to evaluate concordance between self-reported smoking and concentrations of plasma cotinine, a biomarker of smoking, among participants enrolled in two related HIV cohorts. A total of 100 pregnant women (76 living with HIV [LWH] and 24 negative controls) in their third trimester, and 100 men and non-pregnant women (43 LWH and 57 negative controls) were included. Among all participants, 43 pregnant women (49% LWH and 25% negative controls) and 50 men and non-pregnant women (58% LWH and 44% negative controls) were self-reported smokers. The odds of discordance between self-reported smoking and cotinine levels were not significantly different between self-reported smokers and non-smokers, nor between pregnant women and others, but were significantly increased, regardless of self-reported status, among people LWH compared to negative controls. The overall concordance between plasma cotinine and self-reported data among all participants was 94% with a sensitivity and specificity of 90% and 96%, respectively. Taken together, these data demonstrate that participant surveying in a non-judgemental context can lead to accurate and robust self-report smoking data among both persons LWH and not, including in the context of pregnancy.

Age at Natural Menopause in Women Living with HIV: A Cross-Sectional Study Comparing Self-Reported and Biochemical Data.

Early menopause (<45 years) has significant impacts on bone, cardiovascular, and cognitive health. Several studies have suggested earlier menopause for women living with HIV; however, the current literature is limited by reliance on self-report data. We determined age at menopause in women living with HIV and socio-demographically similar HIV-negative women based on both self-report of menopause status (no menses for ≥12 months) and biochemical confirmation (defined as above plus follicle-stimulating hormone level ≥ 25 IU/mL). Multivariable median regression models assessed factors associated with menopause age, controlling for relevant confounders. Overall, 91 women living with HIV and 98 HIV-negative women were categorized as menopausal by self-report, compared to 83 and 92 by biochemical confirmation. Age at menopause did not differ significantly between groups, whether based on self-report (median [IQR]: 49.0 [45.3 to 53.0] vs. 50.0 [46.0 to 53.0] years; p = 0.28) or biochemical confirmation (50.0 [46.0 to 53.0] vs. 51.0 [46.0 to 53.0] years; p = 0.54). In the multivariable model, no HIV-related or psychosocial variables were associated with earlier age at menopause (all p > 0.05). Overall, HIV status per se was not statistically associated with an earlier age at menopause, emphasizing the importance of comparing socio-demographically similar women in reproductive health and HIV research.

The enteric nervous system relays psychological stress to intestinal inflammation.

Mental health profoundly impacts inflammatory responses in the body. This is particularly apparent in inflammatory bowel disease (IBD), in which psychological stress is associated with exacerbated disease flares. Here, we discover a critical role for the enteric nervous system (ENS) in mediating the aggravating effect of chronic stress on intestinal inflammation. We find that chronically elevated levels of glucocorticoids drive the generation of an inflammatory subset of enteric glia that promotes monocyte- and TNF-mediated inflammation via CSF1. Additionally, glucocorticoids cause transcriptional immaturity in enteric neurons, acetylcholine deficiency, and dysmotility via TGF-ß2. We verify the connection between the psychological state, intestinal inflammation, and dysmotility in three cohorts of IBD patients. Together, these findings offer a mechanistic explanation for the impact of the brain on peripheral inflammation, define the ENS as a relay between psychological stress and gut inflammation, and suggest that stress management could serve as a valuable component of IBD care.