Biology subjects

TAO, J.

Publications and source records attributed to TAO, J..

4 recordsLinked to original sources

bioRxiv2026

Short-term oxycodone exposure produces delayed and persistent gut microbiome disruption in mice

The gut microbiome is a critical part of host homeostasis, yet its resilience following opioid exposure remains poorly understood. While opioid-induced short-term dysbiosis is well documented, the long-term recovery dynamics following oxycodone remain unclear. This study characterized the temporal dynamics of the fecal microbiota in male C57BL/6J mice following a brief 3-day oxycodone regimen (5mg/kg, BID). 16S rRNA gene sequencing was performed at baseline, day 3, 10, 17, and 70. While acute post-treatment phases (day 3 to 10) showed subtle taxonomic shifts in Clostridium_sensu_stricto_1 and Romboutsia, significant community disruption emerged later. By day 17, beta diversity significantly differed from saline controls (P =0.002). At day 70, both alpha diversity (p=0.02) and beta diversity (P=0.007) remained significantly altered, characterized by enriched Akkermansia and Marvinbryantia alongside depleted Eubacterium_xylanophilum. These findings demonstrate that even brief oxycodone exposure triggers persistent, non-recovering dysbiosis that became detectable only after treatment cessation and persisted through day 70. This suggests that the window for microbiome recovery exceeds two months in mice (equivalent to several human years), highlighting a potential long-term risk for patients prescribed short-term opioid courses. ImportanceShort-term opioid exposure is generally assumed to cause only transient disruption of the gut microbiome. However, the duration of microbiome recovery following clinically relevant opioid treatment remains poorly defined. In this study, we show that a brief three-day course of oxycodone in mice resulted in delayed and persistent alterations in gut microbial community structure that remained detectable for at least 70 days after treatment cessation. Notably, significant divergence in microbial composition emerged weeks after exposure rather than immediately following treatment, suggesting that short-term opioid use may initiate longer-lasting remodeling of the gut microbiome than previously appreciated. These findings highlight the importance of considering extended recovery timelines when evaluating the microbiological consequences of opioid exposure.

microbiology↗

bioRxiv2025

Neonatal morphine and HIV synergy induce persistent neuroimmune and anxiety-related transcriptional states

BackgroundEarly-life opioid exposure can disrupt neurodevelopment and heighten vulnerability to anxiety and affective disorders, particularly in individuals with HIV. MethodsUsing single-cell RNA sequencing (scRNA-seq), we profiled adolescent brains from wild-type and HIV-1 transgenic (Tg26) mice exposed to morphine during postnatal days 2-7. ResultsMorphine exposure in Tg26 mice resulted in a highly dysregulated microglial phenotype, characterized by the ectopic upregulation of genes encoding neuronpeptides (Avp, Hcrt, and Pmch), while simultaneously showing a reduction in both inflammatory and homeostatic markers (Map3k6, Lgals3, Ccl3). Microglia also showed enhanced expression of dynorphin (Pdyn) and {kappa}-opioid receptor (Oprk1) signaling modules implicated in dysphoria and stress-induced negative effects. Furthermore, transcriptomic mapping revealed cell-type-specific neuronal adaptations: cholinergic neurons upregulated genes linked to anxiety and arousal (Avp, Oxt), GABAergic neurons upregulated genes linked to condition and aversive behavior, whereas glutamatergic neurons enriched for transcripts associated with thigmotaxis and fear behaviors. ConclusionsTogether, these findings demonstrate that brief neonatal morphine exposure in an HIV-inflamed milieu induces persistent, cell-type-specific neuroimmune and neurotransmitter reprogramming that engages the dynorphin-KOR pathway and predisposes to anxiety- and aversion-related behaviors.

neuroscience↗

bioRxiv2025

Albumin-STING Nanocomplex Reprograms HSPCs to Antitumor Neutrophils with Enhanced MHC I Antigen Presentation for Cancer Immunotherapy

Tumor-associated immunosuppressive neutrophils, termed myeloid-derived suppressor cells (MDSCs), compromise cancer immunotherapy. They can be pathologically programmed as early the hematopoietic stem and progenitor cell (HSPC) stage by suppressing interferon signaling. Reprogramming HSPCs toward antitumor neutrophils through the stimulator of interferon genes (STING) activation offers a promising therapeutic strategy. Here, we demonstrate that an albumin-STING nanoagonist (Nano ZSA-51D) reprograms HSPCs to generate antitumor neutrophils, enhancing MHC I-mediated CD8 T cell immunity. Nano ZSA-51D activates STING-interferon signaling in HSPCs, promoting their expansion and differentiation toward granulocyte-monocyte progenitors via STING-NF-{kappa}B-IL-6 signaling. It further reprograms neutrophils into CD14ICAM-1+ subset through STING-NF-{kappa}B-TNF- signaling, enhancing tumor infiltration. These neutrophils upregulate interferon signaling and MHC I antigen presentation, boosting tumor-specific CD8 T cell responses. Adoptive transfer of Nano ZSA-51D-reprogrammed neutrophils with -PD1 therapy achieves complete colon tumor remission. Our findings provide a novel strategy to reprogram HSPCs toward antitumor neutrophils and highlight the potential of early interventions at HSPC stage to rewire neutrophil fate for cancer immunotherapy.

immunology↗

bioRxiv2025

Single-cell transcriptomics reveals probiotic reversal of neonatal morphine-induced gene disruptions underlying adolescent pain hypersensitivity.

Neonatal morphine is commonly administered in the Neonatal Intensive Care Unit (NICU) to manage pain. However, its long-term effects on neurodevelopment of pain pathways, remain a significant concern. The midbrain is a core region that plays a central role in pain processing and opioid-mediated analgesia. Here, we performed single-cell RNA sequencing to study gene expression in 107,427 midbrain single cells from adolescent mice neonatally exposed to either saline, morphine, or morphine with the probiotic Bifidobacterium infantis (B. infantis). We found broad alterations in transcriptomics within neurons, astrocytes, oligodendrocytes, and microglial cells. Analysis of differentially regulated genes revealed down regulation of HOX genes and upregulation of pathways related to neurotransmitter signaling and pain in adolescence that were neonatally treated with morphine. Interestingly, neonatal probiotic supplementation mitigated these morphine-induced alterations on the transcriptome. This study presents the first single-cell RNA sequencing dataset of the adolescent midbrain following neonatal morphine exposure and probiotic intervention. These findings offer new insights into the neurodevelopmental impact of early opioid exposure and highlight the therapeutic potential of microbiome-targeted interventions.

neuroscience↗