Biology subjects

Campen, M.

Publications and source records attributed to Campen, M..

6 recordsLinked to original sources

bioRxiv2026

Nano- and microplastics in pediatric tonsil tissue: bioaccumulation, distribution, and immunomodulatory effects in human lymphoid aggregate organoids

Nano- and microplastics (NMPs), by-products of the fragmentation and degradation of plastic products, are ubiquitous environmental contaminants, yet their burden in pediatric immune tissues and functional consequences for developing immunity remain unknown. Here we report the first comprehensive characterization of NMPs in surgically excised pediatric tonsils (n = 30) using pyrolysis gas chromatography- mass spectrometry (Py-GC/MS), Nile Red fluorescence microscopy, and optical photothermal infrared (O-PTIR) spectroscopy. NMPs were detected in all specimens, with polystyrene, polyethylene, polyethylene terephthalate, and acrylonitrile butadiene styrene present in >90% of samples. To bridge clinical exposure data with mechanistic insight, we formulated a cryo-milled multi-polymer mixture reflecting the patient-derived polymer profile and challenged human lymphoid aggregate culture (HLAC) tonsil organoids at environmentally relevant concentrations. Multiplexed cytokine profiling of culture supernatants revealed a robust early inflammatory response at day 3, with significant upregulation of IL-6 (p = 0.011) and MIP-1{beta}/CCL4 (p = 0.011), followed by convergence toward control levels by day 14. Functional cytokine modules spanning immune, metabolic, structural, and growth factor pathways showed coordinated deviation from controls at day 3 post-exposure with subsequent normalization. Fluorescence-guided depth profiling demonstrated time-dependent penetration of 100 nm particles into organoid aggregates (70% tissue depth at day 3 versus 95% at day 14), and transmission electron microscopy revealed intracellular polyethylene within lymphocyte lysosomes. These findings establish pediatric tonsils as a sentinel tissue for NMP bioaccumulation and demonstrate that environmentally relevant polymer mixtures elicit transient but significant immunomodulatory responses in human lymphoid tissue, with implications for mucosal and systemic immune health in children. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=83 SRC="FIGDIR/small/728317v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@19395f4org.highwire.dtl.DTLVardef@5a0380org.highwire.dtl.DTLVardef@19c0741org.highwire.dtl.DTLVardef@a052c5_HPS_FORMAT_FIGEXP M_FIG Structure: Translational pipeline from clinical tissue characterization to patient-informed preclinical modeling of nano-microplastic (NMP) exposure in pediatric lymphoid tissue. Pediatric tonsil tissue collected from clinically indicated tonsillectomies underwent tissue digestion for NMP characterization to identify NMP type and size distributions. In parallel, tonsil tissue was used to generate human lymphoid aggregate culture (HLAC) organoids that recapitulate the cellular complexity of the native tissue. These patient-derived organoids were then exposed to environmentally relevant compositions and concentrations of NMPs over time-course experiments, with longitudinal assessment of immunomodulatory responses including cytokine profiling and functional readouts. This bedside-to-bench approach establishes a physiologically relevant human system for investigating NMP-immune interactions, bridging clinical tissue analysis with mechanistic preclinical modeling to inform understanding of pediatric environmental exposures and their potential health impacts. C_FIG

immunology↗

bioRxiv2026

Dietary Microplastics Engage Gut Mechanosensory-Endocrine Signaling to Disrupt Bone Homeostasis

Background and AimsMicroplastics are pervasive environmental contaminants increasingly detected in food and water supplies; however, their effects on gastrointestinal physiology and systemic health remain poorly understood. We investigated whether chronic dietary microplastic exposure alters colonic neuroendocrine signaling and skeletal health. MethodsFemale and male C57BL/6J mice were fed purified basal, high-fat/high-cholesterol, or high-fiber diets with or without a physiological relevant polystyrene microplastic mixture ([~]1.7 mg/kg; particle sizes 0.49 - 5.0 {micro}m) for 12 weeks. Colonic cellular responses were evaluated using ELISA, histology, immunofluorescence, and single-nuclei RNA sequencing. Fecal microbiota transplantation was performed to assess microbial contributions to microplastic-induced phenotypes. Bone microarchitecture was assessed by micro-computed tomography. Human bone specimens were analyzed for microplastic content, and primary osteoblast mineralization assays were performed. ResultsDietary microplastic exposure increased chromogranin A-positive enteroendocrine cells and enhanced serotonergic signaling in the colon without evidence of intestinal inflammation or lineage reprogramming. Single-nuclei transcriptomic analysis identified compartment-specific serotonergic and mechanosensory adaptations in epithelial and enteric neuronal populations. Transfer of microbiota from microplastic-exposed donors to control recipients recapitulated increased enteroendocrine cell abundance. Chronic microplastic ingestion induced sex- and diet-dependent reductions in trabecular bone loss and architecture without systemic inflammatory activation. Microplastics were detected in human mineralized bone, and microplastic exposure impaired osteoblast mineralization in a donor-dependent manner. ConclusionsChronic ingestion of microplastics remodels gut neuroendocrine signaling through microbiota-dependent mechanisms and impairs skeletal homeostasis in the absence of overt inflammation. These findings identify a previously unrecognized gut-bone pathway through which dietary microplastic exposure may influence host physiology.

physiology↗

bioRxiv2026

Induction of ferroptotic and amyloidogenic signatures linked to Alzheimers disease by chemically distinct air pollutants

Air pollution (AirP) exposure is associated with increased Alzheimers disease (AD) risk, yet AirP is chemically heterogeneous, complicating identification of shared pathogenic drivers. We examined acute cortical responses to two metal-rich AirP sources, diesel exhaust particles (DEP) and World Trade Center (WTC) dust, and compared them to woodsmoke (WS), a particulate exposure with low metal content. DEP and WTC elicited highly convergent transcriptional responses, sharing over 1200 differentially expressed genes linked to inflammation, ferroptosis, neuronal remodeling, and amyloid processing. These changes were accompanied by impaired antioxidant activity and increased lipid peroxidation within lipid rafts, a membrane microdomain critical for amyloid processing, resulting in increased A{beta} generation. In contrast, WS produced a distinct transcriptional signature and failed to induce ferroptotic priming or lipid peroxidation, consistent with its low metal composition. Together, these findings implicate metals as a shared driver linking diverse AirP exposures to amyloidogenic vulnerability and elevated AD risk. Graphical AbstractAcute AirP exposure converges on ferroptotic priming, amyloidogenic processing, and white-matter vulnerability. Acute exposure to metal-rich AirP, such as DEP or WTC introduces redox-active metals and particulate matter that promote lipid peroxidation, amyloidogenesis, and altered transcriptional regulation in the brain. AirP exposure engages xenobiotic metabolism pathways (AhR/ARNT), activates iron and heme handling through ferritinophagy (NCOA4) and heme oxygenase activity (HMOX1), and blunts lipid peroxide detoxification systems, including glutathione peroxidase 4 (GPx4), ferroptosis suppressor protein 1 (FSP1), and glutathione (GSH) synthesis. These changes promote ferroptotic priming and lipid raft oxidation, facilitating amyloid precursor protein (APP) processing by secretases (ADAM10, BACE1, {gamma}-secretase) and increasing amyloid-{beta} (A{beta}) generation. In parallel, transcriptional and cell-state remodeling involving neuronal and oligodendrocyte responses contribute to selective white-matter vulnerability, particularly within the corpus callosum. Together, these pathways provide a mechanistic framework linking acute AirP exposure to convergent oxidative, amyloidogenic, and microstructural changes relevant to Alzheimers disease pathology. O_FIG O_LINKSMALLFIG WIDTH=197 HEIGHT=200 SRC="FIGDIR/small/696601v1_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@3a22dcorg.highwire.dtl.DTLVardef@c6ae26org.highwire.dtl.DTLVardef@1d3412forg.highwire.dtl.DTLVardef@5cb011_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

In vivo exposure of mixed microplastic particles in mice and its impacts on the murine gut microbiome and metabolome

Microplastics (MPs) are emerging environmental contaminants due to increasing global plastic production and waste. Microplastics, defined as plastic particles less than 5 mm in diameter, are formed through degradation of larger plastics via sunlight, weathering, and microbes. These plastic compounds are widely detected in water, soil, food, as well as human stool and blood. The gut microbiome, often referred to as our second genome, is important in human health and is the primary point of contact for orally ingested microplastics. To investigate the impact of ingested MPs on the gut microbiome and the metabolome, 8 weeks-old male and female C57/BL6 mice were orally gavaged mixed plastic (5 um) exposure consisting of polystyrene, polyethylene, and the biodegradable/biocompatible plastic, poly-(lactic-co-glycolic acid) twice a week for 4 weeks at 0, 2, or 4 mg/week (n = 8/group). Fecal pellets were collected for bacterial DNA extraction and metagenomic shotgun sequencing, and serum was subjected to targeted and untargeted metabolomics. MPs exposure resulted in significant sex-specific and dose-dependent changes to the gut microbiome composition along with substantial regulation of the predicted metabolic pathways. Untargeted metabolomics in serum showed that a low MPs dose displayed a more prominent effect on key metabolic pathways such as amino acid metabolism, mitochondrial function, and inflammation. Additionally, SCFA-targeted metabolomics showed significant changes in neuroprotective SCFAs levels in both sexes by MPs exposure. In conclusion, our study has demonstrated that microplastics dysregulate the gut microbiome and serum metabolome, providing critical insights into potential human disease risks associated with microplastic contamination.

pharmacology and toxicology↗

bioRxiv2025

Plasma Membrane Damage by Environmental Materials Enhances Cell-Cell Fusion and Impairs Immune Functions of Macrophages

Macrophages are the most abundant phagocytes and play an essential role in host defense. Previous studies have shown that many environmental materials can activate macrophages and trigger inflammatory responses. However, whether these exposures alter macrophage function in host defense remains unclear. This study found that many environmental materials (such as carbon nanotubes, tungsten carbide [WC], and detergents) can damage the plasma membranes of macrophages. This damage leads to decreased reactive oxygen species (ROS) production and phagocytosis but elevated cell-cell fusion. In vivo, airway exposure to laundry detergent impaired the recruitment of macrophages and other myeloid cells to the lung and dramatically dampened protective TH1 and TH17 cell responses, leading to increased susceptibility to Candida infection in mice. Overall, our data indicate that exposure to environmental materials compromises macrophage membrane integrity and impairs host defense. These findings may aid in the development of effective preventive and therapeutic strategies.

immunology↗

bioRxiv2023

NEUROMETABOLOMIC IMPACTS OF MODELED WILDFIRE SMOKE AND PROTECTIVE BENEFITS OF ANTI-AGING THERAPEUTICS IN AGED FEMALE C57BL/6J MICE

Wildland fires have become progressively more extensive over the past 30 years in the US, and now routinely generate smoke that deteriorates air quality for most of the country. We explored the neurometabolomic impact that smoke derived from biomass has on older (18 months) female C57BL/6J mice, both acutely and after 10 weeks of recovery from exposures. Mice (N=6/group) were exposed to wood smoke (WS) 4 hours/day, every other day, for 2 weeks (7 exposures total) to an average concentration of 0.448mg/m3 per exposure. One group was euthanized 24 hours after the last exposure. Other groups were then placed on 1 of 4 treatment regimens for 10 weeks after wood smoke exposures: vehicle; resveratrol in chow plus nicotinamide mononucleotide in water (RNMN); senolytics via gavage (dasatanib+quercetin; DQ); or both RNMN with DQ (RNDQ). Among the findings, the aging from 18 months to 21 months was associated with the greatest metabolic shift, including changes in nicotinamide metabolism, with WS exposure effects that were relatively modest. WS caused a reduction in NAD+ within the prefrontal cortex immediately after exposure and a long-term reduction in serotonin that persisted for 10 weeks. The serotonin reductions were corroborated by forced swim tests, which revealed an increased immobility (reduction in motivation) immediately post-exposure and persisted for 10 weeks. RNMN had the most beneficial effects after WS exposure, while RNDQ caused markers of brain aging to be upregulated within WS-exposed mice. Findings highlight the persistent neurometabolomic and behavioral effects of woodsmoke exposure in an aged mouse model. Significance StatementNeurological impacts of wildfire smoke are largely underexplored but include neuroinflammation and metabolic changes. The present study highlights modulation of major metabolites in the prefrontal cortex and behavioral consequences in aged (18 month) female mice that persists 10 weeks after wood smoke exposure ended. Supplements derived from the anti-aging field were able to mitigate much of the woodsmoke effect, especially a combination of resveratrol and nicotinamide mononucleotide.

pharmacology and toxicology↗