Nano- and microparticles are an implicit part of the human diet. They are unknowingly ingested with our food that contains them as additives or pollutants. However, their impact on human health is not yet understood and controversially discussed. The intestinal epithelial barrier shields our body against exogenous influences, such as commensal bacteria, pathogens, and body-foreign particles and, therefore, protects our body integrity. Breakdown of the intestinal epithelial barrier and aberrant immune responses are key events in the pathogenesis of inflammatory bowel disease (IBD). Epithelial lesions might enable systemic translocation of nano- and microparticles into the system, eventually triggering an excessive immune response. Thus, IBD patients could be particularly vulnerable to adverse health effects caused by the ingestion of synthetic particles with food. The food-additive titanium dioxide (TiO₂) serves as a coloring agent in food products and is omnipresent in the Western diet. TiO₂ nanoparticles exacerbate intestinal inflammation by activation of innate and adaptive immune response. Because of serious safety concerns, the use of TiO₂ as a food additive was recently banned from food production within the European Union. Due to environmental pollution, plastic has entered the human food chain, and plastic microparticles have been evidenced in the drinking water and comestible goods. The impact of plastic ingestion and its resulting consequences on human health is currently the subject of intense research. Focusing on TiO₂ and plastic particles in the human diet and their impact on epithelial integrity, gut homeostasis, and intestinal inflammation, this review is addressing contemporary hot topics which are currently attracting a lot of public attention.

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) recently emerged as a promising cancer immunotherapy target. We set out to investigate the functional role of PTPN2 in the pathogenesis of human colorectal carcinoma (CRC), as its role in immune-silent solid tumors is poorly understood. We demonstrate that in human CRC, increased PTPN2 expression and activity correlated with disease progression and decreased immune responses in tumor tissues. In particular, stage II and III tumors displayed enhanced PTPN2 protein expression in tumor-infiltrating T cells, and increased PTPN2 levels negatively correlated with expression of PD-1, CTLA4, STAT1, and granzyme A. In vivo, T cell– and DC-specific PTPN2 deletion reduced tumor burden in several CRC models by promoting CD44⁺ effector/memory T cells, as well as CD8⁺ T cell infiltration and cytotoxicity in the tumor. In direct relevance to CRC treatment, T cell–specific PTPN2 deletion potentiated anti–PD-1 efficacy and induced antitumor memory formation upon tumor rechallenge in vivo. Our data suggest a role for PTPN2 in suppressing antitumor immunity and promoting tumor development in patients with CRC. Our in vivo results identify PTPN2 as a key player in controlling the immunogenicity of CRC, with the strong potential to be exploited for cancer immunotherapy.

Inflammasomes are multi-protein complexes that mediate the activation and secretion of the inflammatory cytokines IL-1β and IL-18. More than half a decade ago, it has been shown that the inflammasome adaptor molecule, ASC requires tyrosine phosphorylation to allow effective inflammasome assembly and sustained IL-1β/IL-18 release. This finding provided evidence that the tyrosine phosphorylation status of inflammasome components affects inflammasome assembly and that inflammasomes are subjected to regulation via kinases and phosphatases. In the subsequent years, it was reported that activation of the inflammasome receptor molecule, NLRP3, is modulated via tyrosine phosphorylation as well, and that NLRP3 de-phosphorylation at specific tyrosine residues was required for inflammasome assembly and sustained IL-1β/IL-18 release. These findings demonstrated the importance of tyrosine phosphorylation as a key modulator of inflammasome activity. Following these initial reports, additional work elucidated that the activity of several inflammasome components is dictated via their phosphorylation status. Particularly, the action of specific tyrosine kinases and phosphatases are of critical importance for the regulation of inflammasome assembly and activity. By summarizing the currently available literature on the interaction of tyrosine phosphatases with inflammasome components we here provide an overview how tyrosine phosphatases affect the activation status of inflammasomes.

Background: The increasing presence of plastics in the human diet is raising public concern about the potential risks posed by nanoplastic (NP) particles, which can emerge from the degradation of plastic debris. NP ingestion poses particular risks to individuals with inflammatory bowel disease (IBD), as compromised epithelial barriers may facilitate NP translocation. Methods: In vitro, bone-marrow-derived macrophages (BMDMs) were exposed to 25 nm polymethacrylate (PMMA) or 50 nm polystyrene (PS) particles to assess morphological changes and alterations in pro- and anti-inflammatory gene expression. In vivo, mice received PMMA NP particles for 6 months before acute dextran sodium sulfate (DSS) colitis was induced to investigate NP impacts on intestinal health and inflammation. Results: PMMA and PS NP exposure in BMDMs induced morphological changes indicative of a proinflammatory phenotype characterized by enlarged amoeboid cell shapes. It also triggered an inflammatory response, indicated by increased expression of proinflammatory cytokines such as Tnfa and Il6. Unexpectedly, long-term PMMA NP administration did not affect the intestinal epithelial barrier or exacerbate acute DSS-induced colitis in mice. Colonoscopy and histological analysis revealed no NP-related changes, suggesting adverse effects on intestinal health or inflammation. Conclusion: Our findings from animal models offer some reassurance to IBD patients regarding the effects of NP ingestion. However, variations in lifestyle and dietary habits may lead to significantly higher plastic intake in certain individuals, raising concerns about potential long-term gastrointestinal effects of lifelong plastic consumption.

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide with limited treatment options for advanced disease stages. Growing evidence implicates the gut microbiota in CRC pathogenesis, prompting interest in probiotics as a potential therapeutic strategy. In this study, we evaluated the effects of two probiotic compositions, CI (a mix of lactobacilli and bifidobacteria) and CII (bifidobacteria alone), in two murine CRC models: the orthotopic MC-38 cecum injection model and the inflammation-driven azoxymethane/dextran sodium sulfate (AOM/DSS) model. CI showed significant anti-tumor effects in the orthotopic model, reducing tumor weight and volume, which was, however, not associated with robust immune activation, suggesting microbiota-driven mechanisms. In contrast, CII was more effective in the AOM/DSS model, reducing colonic inflammation and completely preventing tumor development. Our study demonstrates that probiotics might have great therapeutic potential via modulation of the gut microbiota, and they can exert anti-tumor effects in murine models of CRC with distinct compositions showing differential efficacy depending on the model. CI stabilized the gut microbiome and inhibited pro-tumorigenic taxa in the MC-38 cecum injection model, while CII exhibited anti-inflammatory properties in the AOM/DSS model, highlighting the potential of probiotics as context-specific interventions for CRC. These findings contribute to the growing body of evidence supporting microbiota-targeted strategies in oncology and their relevance for therapeutic applications.

Environmental and genetic factors have been demonstrated to contribute to the development of inflammatory bowel disease (IBD). Recent studies suggested that the food additive; titanium dioxide (TiO₂) might play a causative role in the disease. Therefore, in the present study we aimed to explore the interaction between the food additive TiO₂ and the well-characterized IBD risk gene protein tyrosine phosphatase non-receptor type 2 (Ptpn2) and their role in the development of intestinal inflammation. Dextran sodium sulphate (DSS)-induced acute colitis was performed in mice lacking the expression of Ptpn2 in myeloid cells (Ptpn2^LysMCre) or their wild type littermates (Ptpn2^fl/fl) and exposed to the microparticle TiO₂. The impact of Ptpn2 on TiO₂ signalling pathways and TiO₂-induced IL-1β and IL-10 levels were studied using bone marrow-derived macrophages (BMDMs). Ptpn2^LysMCre exposed to TiO₂ exhibited more severe intestinal inflammation than their wild type counterparts. This effect was likely due to the impact of TiO₂ on the differentiation of intestinal macrophages, suppressing the number of anti-inflammatory macrophages in Ptpn2 deficient mice. Moreover, we also found that TiO₂ was able to induce the secretion of IL-1β via mitogen-activated proteins kinases (MAPKs) and to repress the expression of IL-10 in bone marrow-derived macrophages via MAPK-independent pathways. This is the first evidence of the cooperation between the genetic risk factor Ptpn2 and the environmental factor TiO₂ in the regulation of intestinal inflammation. The results presented here suggest that the ingestion of certain industrial compounds should be taken into account, especially in individuals with increased genetic risk