Anje A. Te Velde

Dietary emulsifiers, common in processed and ultra-processed foods, improve food texture and shelf life but may affect gut health by interacting with the microbiota and intestinal barrier. While emulsifiers have long been considered safe, growing evidence links their presence in ultra-processed foods to chronic disease risk. This review aims to evaluate the current understanding of the factors and mechanisms underlying individual differences in intestinal mucosal susceptibility to dietary emulsifiers. A search of PubMed and Embase through February 2026 identified eight relevant studies. Overall, the available evidence indicates a heterogeneous and highly individualized host response to dietary emulsifiers. These differences appear to be strongly influenced by the gut microbiota and its functional properties, while animal studies further suggest that host factors such as sex-related differences in microbial composition may also contribute to variability in response. Importantly, not all emulsifiers have the same effects, underscoring compound-specific impacts on gut physiology. The findings demonstrate that sensitivity to dietary emulsifiers varies substantially between individuals, challenging the long-standing assumption that these additives are universally safe. Given the multifactorial nature of this susceptibility, particularly the role of the gut microbiota, future research should adopt an integrative approach that combines microbial profiling with host genetics, immune responses, and early-life exposures. Such efforts will be essential to identify at-risk individuals and to inform more personalized dietary recommendations aimed at preserving intestinal health and reducing disease risk. Importantly, there is a clear need for larger, well-powered studies that can validate and expand upon these initial observations.

Background and Aims: Fatigue is a prevalent and disabling symptom in inflammatory bowel disease (IBD), yet its underlying biological mechanisms remain poorly understood. We aimed to characterize fatigue-associated molecular signatures in IBD patients by integrating DNA methylation and mRNA expression analyses. Methods: Peripheral blood was collected from 40 patients with Crohn’s disease (CD), 29 with ulcerative colitis (UC), and 10 healthy controls. Fatigue severity was assessed continuously using the Multidimensional Fatigue Inventory (MFI). Epigenome-wide DNA methylation profiling and mRNA sequencing were performed, identifying differentially methylated regions (DMRs) and differentially expressed genes (DEGs) for active and quiescent CD and UC, adjusting for age, sex, and smoking status. Pathway enrichment analysis was performed on genes with differential methylation and expression. Results: In active CD, more severe fatigue was associated with transcriptional suppression of immune and metabolic pathways (246 DMRs; 1,090 DEGs), versus upregulation of mitochondrial and metabolic processes in quiescent CD (200 DMRs; 1,619 DEGs). In active UC, fatigue was associated with anabolic pathway upregulation and epigenetic silencing of neuroactive pathways (6,927 DMRs; 343 DEGs; 56 concordant genes). Quiescent UC showed transcriptional changes without significant epigenetic pathway enrichment (1,710 DMRs; 3,224 DEGs). Healthy controls exhibited a distinct profile spanning metabolic, immune, and neuronal pathways (8,621 DMRs; 395 DEGs). Fatigue-associated signatures were largely non-overlapping across all five groups. Conclusions: Fatigue-associated molecular profiles differed substantially by disease subtype and activity state, highlighting the biological heterogeneity of IBD-related fatigue and laying the foundation for multi-omics approaches to identify biomarkers and potential therapeutic targets.

Post-acute sequelae of SARS-CoV-2 infection (PASC), also referred to as Long COVID, affects millions worldwide and is characterized by persistent fatigue, reduced immune fitness, and mood disturbances. The aim of the current study was to identify if immune fitness, mood, fatigue, and quality of life prior to SARS-CoV-2 infection could predict PASC fatigue severity. A retrospective cross-sectional survey was conducted among 299 Dutch PASC patients. Participants completed validated measures of immune fitness, fatigue (assessed with both the Fatigue Severity Scale and a single-item scale), mood (including stress, anxiety, depression, hostility, loneliness, and happiness) and quality of life for the three months prior to SARS-CoV-2 infection. The same assessments were made for the month before survey completion (i.e., during PASC). Correlational and regression analyses were conducted to identify possible predictors of PASC fatigue severity. Participants were predominantly female (90%): mean age 44.1 (SD 11.2) years. Both assessments of PASC fatigue did not correlate significantly with the prior SARS-CoV-2 assessments of immune fitness, fatigue, mood, and quality of life. The regression analyses revealed no significant predictors for PASC fatigue severity. In conclusion, immune fitness, fatigue, mood and quality of life prior to SARS-CoV-2 infection were not identified as independent predictors of PASC fatigue severity.

Dietary emulsifiers, common in processed and ultra-processed foods, improve food texture and shelf-life but may affect gut health by interacting with the microbiota and intestinal barrier. While emulsifiers have long been considered safe, growing evi-dence links their presence in ultra-processed foods to chronic disease risk. This review aims to evaluate the current understanding of the factors and mechanisms underlying individual differences in intestinal mucosal susceptibility to dietary emulsifiers. A search of PubMed and Embase through February 2026 identified eight relevant studies. Overall, the available evidence indicates a heterogeneous and highly individ-ualized host response to dietary emulsifiers. These differences appear to be strongly in-fluenced by the gut microbiota and its functional properties, while animal studies fur-ther suggest that host factors such as sex-related differences in microbial composition may also contribute to variability in response. Importantly, not all emulsifiers have the same effects, underscoring compound-specific impacts on gut physiology. The findings demonstrate that sensitivity to dietary emulsifiers varies substantially between individuals, challenging the long-standing assumption that these additives are universally safe. Given the multifactorial nature of this susceptibility, particularly the role of the gut microbiota, future research should adopt an integrative approach that combines microbial profiling with host genetics, immune responses, and early-life exposures. Such efforts will be essential to identify at-risk individuals and to inform more personalized dietary recommendations aimed at preserving intestinal health and reducing disease risk. Importantly, there is a clear need for larger, well-powered studies that can validate and expand upon these initial observations.

Background: Fatigue is a common and debilitating symptom in inflammatory bowel disease (IBD), but its underlying mechanisms remain unclear. Altered tryptophan metabolism may contribute to fatigue. Tryptophan is metabolized through the kynurenine, serotonin, and indole pathway, involving host and microbial processes. We aimed to explore the link between tryptophan metabolism and fatigue, which could lead to the identification of potential biomarkers and therapeutic targets. Methods: Plasma levels of 20 tryptophan metabolites were quantified by liquid chromatography‐tandem mass spectrometry in 38 Crohn's disease (CD), 26 ulcerative colitis (UC) patients and 10 healthy controls. Patients were stratified by disease activity and fatigue severity using the Multidimensional Fatigue Inventory (MFI), and data were evaluated with random forest and ROC analyses. Results: In CD patients, severe fatigue (defined as MFI ≥ 80) was associated with elevated serotonin and reduced kynurenine pathway metabolite levels such as kynurenine, kynurenic acid, and quinolinic acid. These alterations became even more pronounced in quiescent CD. ROC analyses identified kynurenine (AUC = 0.96), kynurenine/tryptophan (AUC = 0.94) and serotonin/kynurenine (AUC = 0.88) as the top discriminators of severe fatigue in quiescent CD. In UC and CD patients with less severe fatigue, these metabolic signatures remained unchanged. Conclusions: Severe fatigue in CD, particularly in quiescent disease, is associated with differences in tryptophan metabolites with low kynurenine pathway metabolite levels and high serotonin levels, which was not observed in UC, suggesting CD‐specific mechanisms. Tryptophan metabolites show potential as biomarkers for severe fatigue and might reveal mechanistic insights relevant for fatigue management in CD.

Inflammatory bowel disease (IBD) is a chronic, immune-mediated gastrointestinal disorder. Although genetic susceptibility contributes to disease risk, it cannot explain the rapidly rising incidence, implicating environmental drivers. Diet has emerged as a key factor, especially the growing global consumption of ultra-processed foods (UPFs), characterised by extensive use of industrial food additives. While epidemiological studies increasingly associate UPF consumption with IBD risk, the underlying biological mechanisms remain insufficiently integrated. This review examines how UPF consumption contributes to IBD pathogenesis and whether dietary modification offers a more comprehensive therapeutic approach than immune inhibition alone. The evidence demonstrates that UPFs, particularly their additive components, disrupt gut homeostasis through converging mechanisms that closely align with IBD pathogenesis. By promoting dysbiosis, impairing mucus and epithelial barrier integrity, inducing endoplasmic reticulum stress, and activating inflammatory pathways such as the NLRP3 inflammasome, food additives sustain the self-perpetuating cycle of intestinal inflammation characteristic of IBD. Although immune dysregulation is central to disease expression, evidence indicates that it is largely driven by upstream disturbances in the gut environment. Current immune-targeted therapies control symptoms but do not address these upstream drivers. In contrast, dietary modulation, particularly reducing UPF exposure, offers a system-level strategy to restore gut homeostasis and complement existing treatments. Together, these findings support a shift in IBD research and management toward targeting upstream drivers of inflammation to improve long-term disease control and ultimately mitigate the growing global burden of IBD.

Research has shown that diet significantly influences the chance of developing chronic inflammatory diseases including inflammatory bowel disease, cardiovascular disease, obesity, type 2 diabetes and several types of cancer. Dietary components modulate the immune system by either promoting or mitigating inflammatory pathways. One such pathway is the activation of the NLRP3 inflammasome—a multiprotein complex that is involved in the innate immune response. The NLRP3 inflammasome is triggered by various stimuli including ionic flux, mitochondrial dysfunction, lysosomal damage and ROS. Upon activation through a two-signal process, an immune response is initiated that protects the body against pathogens and cellular stress. In a healthy body, this pathway is closely regulated to maintain homeostasis and prevent excessive inflammation that can result in tissue damage or chronic inflammatory diseases. Several components present in a human diet can activate or inhibit the NLRP3 inflammasome. To support a balanced diet, organizations like the WHO have developed dietary recommendations. These promote the consumption of fruits, vegetables, whole grains, lean proteins and healthy fats. These foods contain a variety of nutrients and bioactive compounds, including saturated fatty acids, cholesterol, omega-6 fatty acids and natural sugars, which are pro-inflammatory. At the same time, they also supply anti-inflammatory compounds such as monounsaturated fatty acids, antioxidants and probiotics. While current literature highlights the NLRP3 inflammasome as a critical regulator of inflammation, it lacks detailed insights into how the specific dietary components of a healthy diet influence its modulation. Therefore, this literature review elucidates the various mechanisms through which these dietary compounds modulate the NLRP3 inflammasome. The significance of maintaining a balance between pro- and anti-inflammatory components in the diet is highlighted by its role as a regulator of inflammatory diseases, for example, through mechanisms such as epigenetic pathways.