Vitamin D may help reduce the risk of colorectal cancer (CRC) by exerting an anti-inflammatory or modulatory effect on biomarkers associated with the disease. While previous studies have investigated individual biomarkers, our approach evaluates their combined effects. We investigated the association between 25-hydroxyvitamin D (25(OH)D) levels, measured using MS, and the expression of 92 inflammatory biomarkers assessed using the Olink Target 96 inflammation panel. This analysis was conducted in women from the Norwegian Women and Health Study (NOWAC), utilising plasma samples taken 1–6 years prior to CRC diagnosis (n = 163) and 163 matched cancer-free controls. Factor analysis was used to identify biomarker patterns, and linear regression examined the association of each factor with 25(OH)D levels. Women with 25(OH)D deficiency (≤30 nmol/L) had significantly higher Factor 1 scores compared to those with sufficient levels (≥50 nmol/L) (β = 0.72, 95% CI: 0.26–1.18). This association was specific to pre-diagnostic CRC cases (β = 0.97, 95% CI: 0.33–1.60) and was not observed in cancer-free controls (β = 0.22, 95% CI: −0.50–0.93). Factor 1 represents a cluster of biomarkers, many of which are pro-inflammatory (TNFSF14, S100-A12, IL-8, IL-18) and many that play key roles in processes such as cell growth, angiogenesis, and apoptosis (OSM, TGF-alpha, VEGF-A, CASP-8). Several of these biomarkers have been independently linked to CRC, exhibiting both unfavourable and favourable roles. The observed association between 25(OH)D deficiency and Factor 1 in pre-diagnostic CRC cases supports the hypothesis that sufficient levels of vitamin D could potentially contribute to prevention of CRC development.

Treatment-resistant mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD), remain a significant clinical challenge. A confluence of emerging evidence implicates chronic low-grade inflammation in the pathophysiology of at least a subset of mood disorders, potentially mediating their poor response to traditional therapies. Colchicine, a well-established anti-inflammatory agent used in gout and more recently (at low dose) cardiovascular disease, inhibits microtubule polymerisation and suppresses NLRP3 inflammasome activation. Recent advances in immunopsychiatry suggest NLRP3-mediated pathways are key mediators of mood pathology. This hypothesis-generating paper explores how low-dose colchicine may plausibly serve as a novel augmenting agent in refractory mood disorders by targeting these neuroinflammatory pathways. We present mechanistic rationale, integrate preclinical and translational evidence, review long-term safety data and outline biomarker-guided clinical trial proposals.

Intestinal inflammation can lead to inflammation-related diseases such as IBD, so modulation of inflammatory responses is crucial for maintaining homeostasis in the gut and alleviating intestinal inflammation. Autophagy may play a functional role in inflammatory responses and inflammatory signalling pathways. In addition, probiotics can influence important signalling pathways that lead to inflammation. Thus, our objective was to investigate the impact of probiotics on autophagy gene expression to prevent or reduce inflammation by targeting the autophagy signalling pathway. A relative real-time PCR assay was performed to evaluate gene expression involved in the autophagy process after exposing the HT-29 cell line to sonicated pathogens and adding a native potent Lactobacillus/Bifidobacterium cocktail before, after, and simultaneously with inflammation. In general, the native potential Lactobacillus/Bifidobacterium mixture was able to significantly increase autophagy gene expression in all phases and our selected probiotics can influence all phases of the autophagy signalling pathway. Our native Lactobacillus/Bifidobacterium cocktail exhibited a significant impact on the expression of autophagy genes throughout all treatments, particularly during the pre-inflammatory phase. Consequently, our selected probiotics can potentially serve a preventive function in an in vitro model of inflammation.

The maternal diet is believed to influence child neurodevelopment, at least in part, through inflammation, as dietary components can have pro- or anti-inflammatory effects. We examined the association between the energy-adjusted dietary inflammatory index (E-DII) during pregnancy and offspring symptoms of behavioural and emotional problems at 5·5 and 10 years, using data from the French nationwide Etude Longitudinale Française depuis l’Enfance/French Longitudinal Study since Childhood (ELFE) birth cohort. Dietary intake during pregnancy was assessed using a validated FFQ, and an E-DII score was generated. Child behavioural and emotional symptoms, including hyperactivity-inattention, conduct, peer-relationship and emotional problems, were evaluated by parents using the Strengths and Difficulties Questionnaire at 5·5 (n 9627) and 10 years (n 8362) for hyperactivity-inattention, conduct, peer-relationship and emotional problems. Children were classified into three categories based on thresholds used to identify clinically relevant symptoms: ‘Normal’, ‘Borderline’ and ‘Atypical’. Multinomial logistic regression adjusted for potential confounders was used to estimate OR and 95 % CI. An increasing maternal E-DII score during pregnancy was associated with higher odds of offspring classified with atypical hyperactivity-inattention and conduct problem scores at 5·5 and 10 years, atypical peer-relationship problem scores at 10 years and atypical emotional problem scores at 10 years (differentially by sex). A more pro-inflammatory diet during pregnancy was consistently associated with higher odds of symptoms of externalising problems throughout childhood and with internalising problems at 10 years. Future research should explore the mechanisms by which prenatal exposure to maternal diet-induced inflammation may contribute to these outcomes.

Dairy polar lipids have demonstrated anti-inflammatory properties and protective effects on intestinal integrity, potentially mitigating the adverse impacts of weaning in piglets by modulating microbiota composition and intermediary metabolism. This study evaluated a dairy by-product rich in polar lipids on the microbiome and plasma lipid mediators of weaned piglets. A total of 240 male piglets (21 days old; 6.3 ± 0.5 kg) received either a soybean lipid-based diet (SD) or a polar lipid-based diet (PD) from weaning to day 21, followed by a common diet until day 42. Within each diet, animals were provided with one of the three milk replacers (MRs) for the first 7 days: (1) Commercial MR (CO); (2) Polar lipid-based MR (PO); and (3) Soybean lipid-based MR (SO). Fecal and plasma samples were analyzed to assess microbial composition and lipid mediator profiles. Taxonomical distance between diets increased over time, whereas MR type had no effect. The PD diet significantly altered microbiota composition, increasing, for instance, the relative abundance of Firmicutes-belonging genera of the Lachnospiraceae family (Coprococcus, Roseburia), and increasing levels of ethanolamides (e.g., AEA, PEA, SEA, and DPEA). In contrast, the SD diet increased pro-inflammatory lipid mediators (e.g., 13-HODE, 13-KODE) derived from linoleic acid. Polar lipid supplementation in diet, but not in MRs, influenced microbiota diversity and lipid mediator profiles, suggesting a potential long-term impact on immune regulation and metabolism, highlighting their potential to enhance resilience during early-life stress. Future studies should explore these effects under traditional weaning conditions or other stress models.

Current fibre recommendations are based on historical data and may underestimate the intake required for optimal cardiometabolic protection. We examined whether fibre intakes exceeding current guidelines are associated with additional improvements in inflammation and lipid metabolism. We analysed data from 7008 adults (≥ 20 years) from the National Health and Nutrition Examination Survey 2015–2018 with 24-h dietary recall and biomarker data (C-reactive protein (CRP), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides (TAG)). Fibre intake was expressed relative to recommendations from the Institute of Medicine (IOM) and the Academy of Nutrition and Dietetics (AND), and associations with biomarkers were assessed using multivariable regression models. Higher fibre intake was consistently associated with lower CRP concentrations, with the greatest reductions observed at intakes > 150 % of the IOM recommendation (> 55·7 g/d; 95 % CI: 48·6, 56·7). Among men, both TC and LDL-cholesterol decreased significantly at intakes > 150 % of IOM values (> 69·8 g/d; 95 % CI: 64·2, 75·4). TAG were significantly lower when fibre intake exceeded AND recommendations (> 41·0 g/d; 95 % CI: 32·6, 49·5). No clear associations were observed for HDL-cholesterol. The associations found in this study make us consider the possibility that the benefits of fibre on systemic inflammation and lipid profile may extend beyond current recommended levels. Public health guidelines may need to reconsider fibre targets to better reflect condition-specific benefits rather than minimum thresholds for adequacy should this hypothesis be duly proven by future longitudinal studies.

Background: In patients with cyanotic congenital heart disease (CHD), aortopulmonary collateral arteries (APCAs) commonly develop as a compensatory source of pulmonary blood flow. However, APCAs increase pulmonary vascular resistance and ventricular preload, potentially complicating the establishment of Fontan circulation. Coil embolisation of APCAs is routinely performed before Fontan completion, but post-procedural fever is frequently observed and may delay subsequent surgery. This study aimed to identify factors associated with post-embolisation fever, with a particular focus on the influence of coil type. Methods and Results: We retrospectively reviewed 97 paediatric patients who underwent APCA coil embolisation between 2007 and 2023. Patients were categorised according to coil type: platinum coils only (P group, n = 52), both platinum and hydrogel coils (P–H group, n = 29), or hydrogel coils only (H group, n = 16). The incidence of post-embolisation fever (≥38°C) and inflammatory markers were compared among groups. Histopathological characteristics of embolised vessels were also assessed. Overall, post-embolisation fever occurred in 64% of patients. The incidence of fever was significantly lower in the H group (25.0%) than in the P group (73.0%) and P–H group (68.9%) (p < 0.01). C-reactive protein levels increased significantly after fever onset, whereas white blood cell counts showed no meaningful change. Histopathological evaluation demonstrated prominent fibrin deposition and inflammatory cell infiltration in vessels embolised with platinum coils, while vessels treated with hydrogel coils exhibited only mild inflammatory changes. Conclusions: Hydrogel coils were associated with a lower incidence of post-embolisation fever and a milder inflammatory response than platinum coils. These findings suggest that coil selection may play an important role in minimising post-procedural inflammation and facilitating perioperative management in children preparing for the Fontan procedure.

Small-quantity lipid-based nutrient supplements (SQ-LNS) have been shown to improve growth, development and survival among young children in low-resource settings. One hypothesised pathway is through improvements in intestinal health, including modulation of the gut microbiome and reductions in environmental enteric dysfunction (EED). This study examined the effects of SQ-LNS on the gut microbiome and markers of EED and systemic inflammation among young children in Lusaka, Zambia. We conducted intention-to-treat analyses of 302 children aged 27–35 months in a 2 × 2 cluster-randomised trial. Serum biomarkers of EED (soluble CD14, intestinal fatty acid-binding protein) and inflammation (α-1-acid glycoprotein and C-reactive protein) were assessed in 240 children via the Micronutrient and Environmental Enteric Dysfunction Assessment Tool. Differences by SQ-LNS assignment were assessed using unadjusted and adjusted ordinary least squares regression models. Rectal swab samples from 299 children underwent 16S rRNA gene sequencing. Taxonomic profiles were visualised using stacked bar plots, alpha diversity was quantified using Shannon diversity indices and beta diversity was assessed using non-metric multidimensional scaling based on Bray–Curtis dissimilarity matrices. We found that SQ-LNS had no significant effect on EED or inflammation biomarkers and was not associated with differences in gut microbiome α diversity, beta diversity or overall microbial community composition. In exploratory analyses, Enterococcus abundance was lower among children receiving SQ-LNS. Overall, 18 months of SQ-LNS supplementation was not associated with broad changes in intestinal health among young Lusakan children. These findings suggest that the benefits of SQ-LNS operate through pathways other than intestinal health, such as improved nutrient availability.

Acute malnutrition (wasting) remains a global public health problem. Ready-to-use therapeutic foods (RUTF) and supplemental foods (RUSF) for treatment of severe acute malnutrition (SAM) and moderate acute malnutrition (MAM), respectively, come in the form of macro- and micronutrient-dense pastes. These lipid-dense treatments provide the energy and nutrients needed to support growth but have significant rates of relapse. Their role in reversing pathophysiological contributors to malnutrition, such as intestinal barrier dysfunction, intestinal dysbiosis, and systemic inflammation have not been evaluated. Traditional lipid-dense RUTFs and RUSFs are rich in pro-inflammatory omega-6 polyunsaturated fatty acids (PUFAs) but low in anti-inflammatory omega-3 PUFAs, which could fuel malnutrition-related pathological inflammation. We reasoned that reduced dietary omega-6 (n-6) PUFAs and increased dietary long-chain omega-3 (n-3) PUFAs found in fish oil would reduce malnutrition-related pathological inflammation. In an established mouse model of MAM, we observed that altering the dietary n-3/n-6 PUFA ratio through replacing dietary corn oil with fish oil improved the diversity and composition of the caecal microbiota, improved intestinal mucosal barrier and immune defence, reduced translocation of bacteria and bacterial lipopolysaccharides (LPS), and dampened systemic inflammation. Furthermore, dietary fish oil protected against weight loss upon systemic challenge with bacterial LPS. The anti-inflammatory effects of dietary fish oil did not compromise host defence against challenge with the intestinal pathogen, Citrobacter rodentium. Collectively, these results suggest that dietary fish oil blunts inflammation that contributes to the pathogenesis of MAM. Inclusion of fish oil in dietary interventions may be beneficial in prevention or reduction of malnutrition-associated inflammation.

The β-galactoside-binding protein galectin-3 is currently a hotly pursued therapeutic target in cancer, inflammation and fibrosis-associated diseases due to its multi-mode actions and broad impact on the pathogenesis and progress of the diseases. Various natures of galectin-3 inhibitors have been developed and investigated, and several have shown promising results in early-phase clinical trials. All these galectin-3 antagonists were designed to target the canonical carbohydrate-binding site, the S-face, of the galectin-3 carbohydrate recognition domain (CRD). This review discussed the current galectin-3 antagonists and explored their modes of actions, focusing particularly on their targeting regions on galectin-3. It discussed the tri-modular structure of galectin-3 and the roles of different segments in galectin-3 actions. It proposed that, in addition to the canonical carbohydrate-binding sites on the S-face, the non-canonical carbohydrate-binding interface, the F-face of the galectin-3 CRD as well as its flexible N-terminal domain are also targetable in the design of galectin-3-targeted therapeutics. Given the high degree of structural similarities of CRDs among galectin family members but unique nature of galectin-3 N-terminus, antagonists developed against the N-terminal domain of galectin-3 can potentially offer greater target specificity by avoiding cross-reactivity with other galectin members. Antagonists that can interact with more than one segment of galectin-3, or a combination of antagonists against different galectin-3 segments, may potentially provide improved efficacy and therapeutic effectiveness for treatment of galectin-3-mediated pathologies and diseases.