The increasing and global distribution of microplastics and nanoplastics (MPs/NPs) in the environment has led to concern about their potential influence on human health, especially on the gastrointestinal tract, as well as the brain. MPs/NPs could traverse epithelial and endothelial barriers, disrupt the gut microbiota, and perturb the microbiota–gut–brain axis, leading to systemic inflammation and possibly extending neurodegenerative processes. Experimental models now demonstrate that MPs/NPs reprogram nuclear and mitochondrial epigenetics—DNA methylation, histone modifications, non-coding RNAs, and mitochondrial DNA regulation—in gut, immune, and neural cells with downstream effects on synaptic function, neuronal survival, and protein aggregation. This mechanistic narrative review integrates preclinical and emerging human evidence of how MPs/NPs compromise intestinal barrier integrity, modulate gut microbiota composition, affect the blood–brain barrier, and converge on oxidative stress, neuroinflammatory signaling, and cell death pathways within the central nervous system across key neurodegenerative diseases. Overall, the review offers an integrated model in which environmental exposure to chronic MPs/NPs disrupts the microbiota–gut–brain axis and drives concurrent nuclear and mitochondrial epigenetic remodeling, lowering the threshold for neurodegeneration in susceptible individuals, while outlining candidate mechanistic readouts that require exposure-specific validation in human-relevant models and longitudinal cohorts.

Mesenchymal stem cells (MSCs) are recognized for their capacity to modulate immune responses, including those directed against tumors. In this study, we investigated the temporal effects of MSCs administration on anti-tumor immunity in a murine 4T1 breast cancer model. BALB/c mice were intraperitoneally injected with MSCs either 24 h (MSC1d) or 14 days (MSC14d) after orthotopic implantation of 4T1 mammary carcinoma cells. Early MSC administration (MSC1d) exhibited changes in immune cell phenotypes consistent with enhanced antitumor potential, including increased activity of natural killer (NK) cells, dendritic cells (DCs), macrophages, and T lymphocytes. These immunological changes correlated with reduced tumor growth and prolonged survival. Mice in the MSC1d group exhibited elevated serum levels of pro-inflammatory and anti-tumor cytokines (TNF-α, IFN-γ, IL-6, and IL-17), alongside decreased concentrations of immunosuppressive cytokines (TGF-β and IL-10). Tumor tissue analysis revealed increased infiltration of NK cells expressing markers associated with antitumor activity (IFN-γ-producing CD178⁺), CD80⁺/CD86⁺/I-A⁺ TNF-α-producing DCs, Th1-type CD4⁺ T cells, and Granzyme B-expressing CD8⁺ cytotoxic T lymphocytes (CTLs). Additionally, spleens of MSC1d-treated mice displayed significantly elevated populations of CD11c⁺ DCs, TNF-α/IFN-γ-secreting NK cells, CD4⁺ Th1 and Th17 cells, and CD8⁺ CTLs expressing markers associated with cytotoxic function (TNF-α, IFN-γ, and IL-17). Conversely, late MSCs administration (MSC14d) was associated with immunosuppression. Tumors from MSC14d-treated mice showed a decreased presence of IFN-γ⁺ and IL-17⁺ NK1.1⁺ cells, F4/80⁺ macrophages, IL-12⁺ DCs, and cytotoxic T cells. Spleens from these mice revealed a significant expansion of regulatory T cell (Treg)-like populations, including CD25⁻, FoxP3⁻, CD25⁺FoxP3⁻ cells, and TGF-β/IL-10-producing CD3⁺ and CD4⁺ T cells. Furthermore, serum levels of immunosuppressive mediators TGF-β and vascular endothelial growth factor (VEGF) were significantly elevated in the MSC14d group. Collectively, these findings demonstrate that the immunomodulatory effects of MSCs on breast cancer are highly dependent on the timing of their administration. Mesenchymal stem cells delivered during early tumor development enhance phenotypes consistent with antitumor potential and suppress tumor progression, whereas administration during later stages promotes immune evasion and tumor growth.

Non-celiac gluten sensitivity (NCGS), even though it is a term defined for more than four decades, is still an enigmatic clinical entity. This is primarily due to the absence of specific diagnostic criteria, with most reports relying on patients’ self-diagnosis. Individuals with NCGS experience intestinal (abdominal pain, bloating, diarrhea, or constipation) and extraintestinal symptoms (“foggy mind,” depression, anxiety, and deterioration of psychiatric conditions) after gluten consumption. Frequent disregard and oversight of extraintestinal manifestations, such as psychiatric symptoms, further complicates NCGS. The lack of understanding about NCGS causes individuals living with this condition to experience distress, frustration, and stigmatization. An impaired intestinal barrier, gut dysbiosis, and alterations in the gut–brain axis are proposed as key factors in the NCGS and psychiatric symptoms associated with NCGS. None of these links are yet definitive, and the methodological limitations of existing studies—small samples, self-reported diagnoses, and insufficient blinding—demand that conclusions be drawn with appropriate restraint. The purpose of this review is to provide an up-to-date understanding of the pathophysiology of NCGS and psychiatric symptoms associated with NCGS. Future studies should focus on development of reliable, objective diagnostic markers for NCGS and on the design of adequately powered, double-blind, placebo-controlled trials that incorporate validated psychiatric outcome measures alongside intestinal indices.