Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2024.12.20.629591

Deleterious imprinting of perinatal exposure to nano-polystyrene on inflammatory bowel diseases

Airaud, M.·Roldan, A.·Le cleach, J.·Isoard, L.·Mas, E.·Carriere, M.·Menard, S.·Barreau, F.
View original source ↗Export metadata ↓

Abstract

The tremendous and exponential production of plastics as well as its poor recycling leads to massive release in the environment questioning their outcomes on human health. Plastics are degraded into micro-plastic (MPL) and nano-plastic (NPL) that undergo weathering. MPL and NPL enter the human food chain via contaminated food, when animals are bred or vegetables grew on in plastic polluted environment and through the degradation of plastics food packaging. Ingested MPL or NPL can pass through epithelial barrier. This study focuses on consequences of oral perinatal exposure to polystyrene 50nm pristine or weathered (w) on intestinal disorders onset in offspring. Mouse were forced fed daily with 1.25mg of PS50 or PS50w starting at 15 days of gestation until pups weaned (Post Natal Day PND21). Oral tolerance protocol was induced at PND15 (nutritional switch) with ovalbumin (OVA) whereas DSS-induced colitis was performed in PND63 offspring. PS50 nor PS50w perinatal exposure did impair tolerance or immunization to OVA at PND15 in male or females. However, PS50 and PS50w perinatal exposure significantly worsened macroscopic score of DSS-induced colitis in both sexes. Perinatal exposure to PS50w appeared to be even more deleterious than PS50 for colitis exacerbation in males. In conclusion, early life exposure to PS50 or PS50w has long-lasting consequences on gut physiology by increasing the colonic severity of colitis while it does not modify oral tolerance establishment in early life. Those preliminary results questioned the kinetic of perinatal PS50 and PS50w exposure outcome over the life course and introduce the notion of imprinting. HighlightsO_LIPerinatal exposure to PS50 or PS50w does not affect oral tolerance establishment nor immune response to immunisation at PND15 C_LIO_LIPerinatal exposure to PS50 or PS50w have long lasting consequences on intestinal inflammation and colitis. PS50w in male has even more deleterious outcomes. C_LIO_LIRestricted exposure to PS50 or PS50w during perinatal has a deleterious imprinting on adult offspring intestinal health C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=82 SRC="FIGDIR/small/629591v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@13bae52org.highwire.dtl.DTLVardef@131b42eorg.highwire.dtl.DTLVardef@2c7317org.highwire.dtl.DTLVardef@380df8_HPS_FORMAT_FIGEXP M_FIG C_FIG Environmental implicationThe use of plastics in daily products leads to ubiquitous contamination of the environment and subsequently of food chains. Plastics persist for long periods in the environment where, submitted to climate, they fragment into nanoplastic particles (NPL). Indeed, these NPL are weathered due to their exposure to UV light, thermal, chemical, physical and biological stresses. Thus, human populations are exposed to pristine (NPLp) and weathered NPL (NPLw) in their daily lives, with unknown effect on intestinal health, including the diseases development like adverse Food Reactions (AFR) or Inflammatory Bowel Diseases (IBD). Given that these pathologies could originate in perinatal development and that pregnant and breastfeeding women are exposed to NPL on a daily basis, this study explores the impact of perinatally exposure to pristine or weathered polystyrene nanoplastics on the gut development and susceptibility.

Source connections

Explore related subjects

pathologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Airaud, M., Roldan, A., Le cleach, J., Isoard, L., Mas, E., Carriere, M., Menard, S., Barreau, F.. 2024-12-22. Deleterious imprinting of perinatal exposure to nano-polystyrene on inflammatory bowel diseases. https://doi.org/10.1101/2024.12.20.629591

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Autophagic flux is increased in peripheral blood mononuclear cells in atherosclerotic vascular disease and associates inversely with adverse cardiovascular events

Background: Autophagy is a homeostatic pathway supporting stress adaptation and is dysregulated in atherosclerosis. Its potential as a biomarker or therapeutic target in atherosclerotic vascular disease (ASVD) remains incompletely defined. We measured autophagic flux in peripheral blood mononuclear cells (PBMCs) from patients with peripheral arterial disease (PAD) or carotid stenosis (CS), compared with healthy controls, and explored clinical outcome associations. Methods: Ninety-four patients with PAD or CS and 19 healthy controls were studied. Autophagic flux was quantified from fresh blood using a validated ex vivo chloroquine inhibition ELISA measuring LC3BII accumulation. Major adverse cardiovascular events (MACE) and major adverse limb events (MALE) were ascertained over a median follow up of 828 days. Results: The ASVD cohort comprised claudication (n = 16), chronic limb threatening ischemia (CLTI; n = 49), and CS (n = 29). Autophagic flux was higher in ASVD than controls (mean 281.4 vs. 182.3 ng LC3BII/mg protein/h; p < 0.0001) and remained independently associated after multivariable adjustment. Within CLTI, concurrent infection was associated with lower flux (p = 0.001), approaching control levels (p = 0.327). In CLTI, higher flux quartiles were associated with lower MACE risk, most strongly for quartile 3 (hazard ratio 0.07 vs. quartile 1, 95% CI 0.01 to 0.50; p = 0.009). Conclusion: Autophagic flux is elevated in PBMCs from ASVD patients, independent of age and sex. Attenuated flux in CLTI with concurrent infection may indicate autophagic exhaustion in advanced disease. The association between higher flux and lower MACE in CLTI suggests prognostic utility, warranting evaluation in larger prospective studies.

pathology↗
bioRxiv2026

Quantitative Model of the Ocular Immune Response during Seasonal Allergic Conjunctivitis

Allergic conjunctivitis is an inflammation of the conjunctiva caused by allergen; it is common disorder affecting up to 40% of the population. In this work, we study seasonal allergic conjunctivitis (SAC), also called "hay fever eyes", which is caused by exposure to airborne pollens. We develop a mathematical model quantifying the ocular immune system response to the allergens. First, we present a simplified qualitative description of the immunopathogenesis of SAC. Then, we express each chosen immunopathological mechanism mathematically to construct a system of thirty-one ordinary differential equations. We compare summary statistics of the predicted observable immune signals to experimental measurements and find our model captures key qualitative features of SAC progression. We then compare our predicted time series of histamine concentration to symptom scores and find a strong correlation suggesting the model predicts relevant clinically trends. Next, we calibrate the model through multi-step process. We find the most influential parameters are the production and depletion rates of IL-4, and the production rates of IL-5 and IL-8. These cytokines are targeted in treatments for asthma, atopic dermatitis, and severe eosinophilic associated disorder and suggest potential therapeutic targets for SAC. Our calibrated model mimics most of the summary statistics of the experimentally observable immune signals with discrepancies for IL-5 and IL-13 indicating that additional immunopathological mechanisms could be important.

pathology↗
bioRxiv2026

Dysregulated Platelet GPIb alpha - VWF Signalling in Abdominal Aortic Aneurysm formation and Progression

Background: Platelets are critical drivers of thrombo-inflammatory responses in different cardiovascular diseases. Abdominal aortic aneurysm (AAA) is a progressive, life-threatening vascular disorder mainly characterised by chronic inflammation, extracellular matrix degradation, and the formation of a platelet-rich intraluminal thrombus (ILT). Experimental and clinical evidence identified platelets as main players in AAA pathology as evidenced by elevated platelet activation and procoagulant activity that critically contribute to AAA progression. Methods: The present study investigated the contribution of glycoprotein (GP)Ib alpha, the von Willebrand factor (VWF)-binding subunit of the platelet GPIb-IX-V complex, to AAA initiation and progression in experimental AAA using the ePPE mouse model and in patients. Results: Genetic ablation of platelet GPIb alpha significantly attenuated early aneurysm expansion in experimental AAA, indicating a critical role for GPIb alpha during the initial stages of aneurysm development. This initial effect was compensated at later time points showing no differences in aneurysm progression between groups. Notably, genetic deletion of GPIb alpha induced a constitutively hyperactive platelet phenotype already in naive mice that was further amplified during experimental AAA. This elevated platelet hyperactivity was mainly due to increased GPVI activation of platelets 28 days post-surgery. To assess the clinical relevance, spatial profiles of human ILT specimens from patients with AAA were analysed. In the ILT, we detected a highly compartmentalised distribution of GPIb alpha and VWF with pronounced enrichment within the luminal layer. In parallel, circulating VWF activity as well as platelet surface expression of GPIb alpha were significantly increased in patients with AAA. Conclusion: Collectively, these findings identify a dysregulated GPIb alpha-VWF axis in human AAA pathology, mainly characterised by enhanced platelet GPIb alpha surface expression and increased activity of circulating VWF.

pathology↗