Biology subjects

Phatak, S.

Publications and source records attributed to Phatak, S..

3 recordsLinked to original sources

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↗

bioRxiv2024

The Ratchet Model of Synovial Flares in Palindromic Rheumatism

Synovial flares in palindromic rheumatism (PR) are aperiodic bursts of inflammation in the joints, which usually self-resolve in a timescale hours or days. PR patients are believed to transit to a chronic auto-immune disease called rheumatoid arthritis (RA) in most cases, however, many patients remain palindromic indefinitely. We utilize and adapt a minimal ODE model of rheumatoid arthritis (RA) developed by Baker et al. to study PR in greater detail. We address questions characterizing the incidence, decay and sustenance of synovial flares in palindromic patients. A key question is to describe the nature of the transition from palindromic to full RA. We show that PR flares ordinarily resolve spontaneously, however, there is a secondary equilibrium in the model into which the trajectory can sometimes get trapped. When this "meta-stable locking" occurs, it initiates an adaptation that helps rescue the flare. Furthermore, this adaptation in turn activates a secondary adaptation in response to fluctuations in the healthy steady state. Finally, we show that if metastable locking occurs frequently enough these adaptation sequences turn maladaptive and the system slowly progresses into fully developed RA.

immunology↗

bioRxiv2024

Withaferin A reduces pulmonary eosinophilia and IL-25 production in a mouse model of allergic airways disease

Several studies report that ashwagandha, a traditional Ayurvedic supplement, has anti-inflammatory properties. Type 2 (T2) asthma is characterized by eosinophilic airway inflammation. We hypothesized that allergen-induced eosinophilic airway inflammation in mice would be reduced following administration of Withaferin A (WFA), the primary active phytochemical in Ashwagandha. C57BL/6J mice were given 10 total intra-peritoneal injections of 2 mg/kg WFA or vehicle control, concurrent with 6 total intranasal administrations of 50 {micro}g house dust mite extract (HDM) or saline control over 2 weeks. We observed that treatment with WFA reduced allergen-induced peribronchial inflammation and airway eosinophil counts compared to mice treated with controls. In addition, we observed that treatment with WFA reduced lung levels of interleukin-25 (IL-25) but increased lung gene expression levels of its co-receptor, Il17ra, in HDM-challenged mice compared to HDM-challenged mice that received the vehicle control. This study pinpoints a potential mechanism by which WFA modulates allergen-induced airway eosinophilia via the IL-25 signaling pathway. Future studies will investigate the effects of WFA administration on lung eosinophilia and IL-25 signaling in the context of chronic allergen-challenge.

immunology↗