The disruption of the intestinal barrier and the imbalance of the gut microbiota (GM) seem to play a major role in the complex pathogenesis of irritable bowel syndrome (IBS). Specific microbial strains could improve the gut microenvironment, promoting anti-inflammatory pathways; similarly, vitamin D supplementation could play a role in enhancing the barrier integrity and modulating the immune response in the gut. This study aims to evaluate the efficacy of a new multistrain probiotic, combined with vitamin D, in improving gut barrier function in IBS without constipation.

In this phase IIb double-blind randomized placebo-controlled, parallel-group, multicenter, clinical trial, 35 patients were treated for 12 weeks with OttaBac®, a high concentration multistrain probiotic plus cholecalciferol, or placebo and were followed up until week 16. Symptoms, quality of life, intestinal permeability, fecal biomarkers, and microbiota composition were evaluated at 0, 12, and 16 weeks.

Mean zonulin values showed a significant progressive reduction in the active group (-10.2 ng/mL at week 12, p = 0.0375; -19.5 ng/mL at week 16, p = 0.0002), with a significant difference between groups at week 16 in the per-protocol population (-19.01, p = 0.0053). The active group showed a more stable trend toward improvement in stool frequency and consistency at both week 12 and 16, with a significant improvement compared to the baseline and to the placebo group (-23.2, p = 0.0265, and 5.57 vs. -23.2, p = 0.0492, respectively). No differences were found in regards to the lactulose/mannitol ratio, Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) and Short Form Health Survey (SF-36) total scores, plasmalemmal vesicle associated protein-1 (PV-1), and citrulline levels. In the active group, Bifidobacterium animalis subsp. lactis and Streptococcus thermophilus levels were increased (p < 0.05), while those for Lachnospira were decreased (p < 0.05), and significant changes in Actinobacteria and Proteobacteria were observed (p < 0.05). Lactate (p < 0.01) and acetate (p < 0.05) levels increased post-treatment. Correlation analysis pointed out a significant association between the microbial biomarkers and the symptoms (p < 0.05).

Probiotic plus vitamin D could improve IBS-associated symptoms through gut microbiota modulation and gut barrier enhancement, with persistent benefits after treatment discontinuation.

The human gut microbiome represents a complex ecosystem comprising numerous microorganisms critical to basic physiological processes. The gut microbiome's composition and functionality influence surgical outcomes following orthopedic procedures. The purpose of this study was to evaluate the gut microbiota on critical aspects of orthopedic surgical outcomes. A comprehensive literature search was conducted via PubMed, the Cumulative Index for Nursing and Allied Health Literature (CINAHL), Google Scholar, Cochrane Library, Medline, and Web of Science. A total of 18 research articles of the 599 retrieved results were included in this study. Significant correlations were identified between microbial composition and surgical outcomes, including infection rates, inflammatory responses, and postoperative complications. Bacterial genera like Alistipes and Helicobacter increased postoperative cognitive dysfunction (POCD) risk, while short-chain fatty acid (SCFA)-producing bacteria showed negative correlations with inflammatory markers. Probiotic interventions reduced POCD incidence from 16.4% to 5.1% and modulated inflammatory responses. Additionally, bacterial composition was associated with critical surgical parameters such as bone healing, infection rate, and recovery trajectory. Inflammation, healing processes, and recovery trajectories are influenced by microbial composition in surgical settings. Targeted interventions, such as probiotics, show promise in reducing surgical risks and improving patient recovery.

Inflammatory bowel disease (IBDs), including Crohn's disease (CD), and ulcerative colitis (UC) are complex diseases with a multifactorial etiology, associated with genetic, dietetic, and other environmental risk factors. Children with IBD are at increased risk for nutritional inadequacies, resulting from decreased oral intake, restrictive dietary patterns, malabsorption, enhanced nutrient loss, surgery, and medications. Follow-up of IBD children should routinely include evaluation of specific nutritional deficits and dietetic and/or supplementation strategies should be implemented in case deficiencies are detected. This narrative review focuses on the prevalence, risk factors, detection strategy, and management of micronutrient deficiencies in pediatric IBD.

Microplastics are pervasive environmental pollutants, attracting significant concern due to their potential adverse effects on ecosystems and human health. This study hypothesizes that microplastics may significantly impact gastrointestinal (GI) health through various mechanisms. The objective of this systematic review is to explore the effects of microplastics on GI health, focusing on animal models such as mice, fish and earthworms.

A systematic review approach was employed, analyzing studies that investigate the impact of microplastics on the gut microbiota, gut barrier integrity and GI inflammation. The review includes a synthesis of findings from multiple animal models.

The review reveals consistent evidence that microplastics can disrupt the gut microbiota, impair the gut barrier, and induce inflammatory responses in the GI tract. Statistical analysis shows a significant correlation between microplastic exposure and GI health deterioration across various animal models.

The findings underscore the harmful effects of microplastics on GI health, emphasizing the urgent need for policy interventions to reduce plastic pollution. Implementing measures to limit the production and usage of disposable plastics is crucial for mitigating the risks posed by microplastic contamination to promote environmental sustainability and safeguard human well-being.

As broiler breeder hens age, they often experience a decline in bone mineralization and calcium absorption, especially during the later stages of egg production. This issue not only affects the hens' health, making them more prone to conditions like osteoporosis, but it also impacts the quality of their offspring. To tackle this problem, our study explores whether supplementing these hens with a combination of vitamins D3 and C could help improve their bone health and overall biochemical balance, both for them and their progeny. The goal of this research was to evaluate the effects of high doses of vitamin D3, with and without added vitamin C, on bone mineralization and key blood parameters in aging broiler breeder hens and their offspring. In this experiment, 240 hens and 24 roosters from the Ross 308 strain, aged between 49 and 61 weeks, were used, and a two-way ANOVA (2 × 2) design was applied. This involved two levels of vitamin D3 (3,500 IU and 5,500 IU) and two levels of vitamin C (0 and 150 mg/kg), with six replications of 10 hens and one rooster per group. At the end of the study, blood samples were collected from hens and their offspring for biochemical analysis, and tibia bones were taken for ash content and mineralization assessment. The findings showed that vitamin D3 supplementation significantly lowered blood cholesterol, alkaline phosphatase (ALP), and parathyroid hormone (PTH) levels (P < 0.05), while boosting calcium, 25-hydroxycholecalciferol (25(OH)D3), and 1,25-dihydroxycholecalciferol (1,25(OH)2D3) (P < 0.05). Higher doses of vitamin D3 also improved the strength, resistance, and ash content of the hens' tibia bones, and increased calcium in the carcasses of their offspring. Adding 150 mg/kg of vitamin C to the diet also had a positive effect, reducing cholesterol, ALP, and PTH, while enhancing plasma calcium, total antioxidant capacity, and the active form of vitamin D3 (P < 0.05). Vitamin C supplementation significantly strengthened the tibial bones of the hens and improved plasma calcium and PTH levels in their offspring (P < 0.05). Interestingly, combining elevated doses of both vitamins D3 and C resulted in even greater improvements in tibial bone strength (P < 0.05). In conclusion, giving hens 150 mg of vitamin C along with 5,500 IU of vitamin D3 leads to substantial improvements in the calcium content and structural integrity of their bones, and also boosts calcium and ash content in the carcasses of their offspring.

Vitamin B12 (cobalamin) plays a crucial role in neurodevelopment, particularly during pregnancy and early childhood. It is essential for DNA synthesis, red blood cell formation, and nervous system function. Maternal B12 levels are particularly important, as they influence fetal brain development. Inadequate maternal intake during pregnancy may lead to altered neurodevelopmental trajectories and increase the risk of ASD. Postnatally, insufficient dietary cobalamin in infants and young children could further contribute to cognitive and behavioral impairments. One potential mechanism linking low B12 levels to ASD involves its role in the gut microbiota balance. Dysbiosis, commonly observed in individuals with ASD, is associated with increased gut permeability, low-grade inflammation, and disruptions in the gut-brain axis, all of which may contribute to ASD symptoms. Additionally, B12 is essential for neurotransmitter metabolism, particularly in the synthesis of serotonin and dopamine, which regulate mood, cognition, and behavior. Cobalamin also plays a key role in neuronal myelination, which ensures efficient signal transmission in the nervous system. Disruptions in these processes could underlie some of the cognitive and behavioral features associated with ASD. Despite growing evidence, the link between B12 and ASD remains inconclusive due to inconsistent findings across studies. Research suggests that B12 levels may serve as a potential biomarker for disease progression and treatment response. However, many studies rely on single-time-point measurements, failing to account for individual variability, genetic predispositions, dietary intake, and environmental factors, all of which can influence B12 levels and ASD risk. Further longitudinal studies are needed to clarify this relationship.

Gastrointestinal homeostasis describes a delicate state of equilibrium in which various systems cooperate to maintain digestive health, support microbial activity, and regulate immune responses. There is growing evidence that Vitamin D is one of the many factors that influences gastrointestinal homeostasis through its effects on gut barrier integrity, regulating microbial diversity and modulating immune responses. Given these effects of Vitamin D, there may be potential for it as both a preventative and a therapeutic intervention for a variety of conditions, but especially for inflammatory conditions of the gastrointestinal tract. This article will summarize the role of Vitamin D in a state of equilibrium, as well as its role in a pro-inflammatory state in the gastrointestinal tract.

Proper regulation of intestinal permeability is essential for maintaining the integrity of the intestinal mucosal barrier. An abnormal increase in permeability can significantly contribute to the onset and progression of various diseases, including autoimmune disorders, metabolic conditions, allergies, and inflammatory bowel diseases. The potential connection between intestinal permeability and maternal health during pregnancy is increasingly recognized, yet a comprehensive review remains lacking. Pregnancy triggers a series of physiological structural adaptations and significant hormonal fluctuations that collectively contribute to an increase in intestinal permeability. Although an increase in intestinal permeability is typically a normal physiological response during pregnancy, an abnormal rise is associated with immune dysregulation, metabolic disorders, and various pregnancy-related complications, such as recurrent pregnancy loss, gestational diabetes mellitus, overweight and obesity during pregnancy, intrahepatic cholestasis of pregnancy, and preeclampsia. This paper discusses the components of the intestinal mucosal barrier, the concept of intestinal permeability and its measurement methods, and the mechanisms and physiological significance of increased intestinal permeability during pregnancy. It thoroughly explores the association between abnormal intestinal permeability during pregnancy and maternal diseases, aiming to provide evidence for the pathophysiology of disease development in pregnant women. Additionally, the paper examines intervention methods, such as gut microbiota modulation and nutritional interventions, to regulate intestinal permeability during pregnancy, improve immune and metabolic states, and offer feasible strategies for the prevention and adjuvant treatment of clinical pregnancy complications.

In addition to its classical role in calcium and phosphate metabolism regulation, vitamin D also has an important impact on immunity modulation. Vitamin D regulates the immune response, shifting from a proinflammatory state to a more tolerogenic one by increasing the release of anti-inflammatory cytokines while downregulating proinflammatory cytokines. Thus, low levels of vitamin D have been associated with an increased risk of developing autoimmune diseases like multiple sclerosis and type 1 diabetes. Furthermore, this prohormone also enhances the release of well-known antimicrobial peptides, like cathelicidin LL-37 and β-defensins; therefore, it has been proposed that vitamin D serum levels might be related to the risk of well-known pathogen infections, including herpesviruses. These are a group of widely spread viral pathogens that can cause severe encephalitis or tumors like Kaposi's sarcoma and Burkitt lymphoma. However, there is no consensus on the minimum levels of vitamin D or the recommended daily dose, making it difficult to establish a possible association between these two factors. This narrative non-systematic review will analyze the mechanisms by which vitamin D regulates the immune system and recent studies about whether there is an association between vitamin D serum levels and herpesvirus infections.

The importance of vitamin D for a well-functioning immune system is becoming increasingly evident. Nevertheless, the other fat-soluble vitamins A, E and K also seem to play a central role regarding the adequate function of immune cells and to counteract excessive immune reactions and inflammatory processes. However, recognizing hidden hunger, particularly micronutrient deficiencies in vulnerable groups like the elderly, is crucial because older adults often lack sufficient micronutrients for various reasons. This review summarizes the latest findings on the immune modulating functions of fat-soluble vitamins in a physiological and pathophysiological context, provides a graphical comparison of the Recommended Daily Allowances between Deutschland, Austria, Confoederatio Helvetica (D-A-CH; eng. GSA, Germany, Switzerland, Austria), Deutsche Gesellschaft für Ernährung (DGE; eng. German Nutrition Society) and National Institutes of Health (NIH) across all age groups and, in particular, addresses the question regarding the benefits of supplementation of the respective micronutrients for the aging population of industrialized nations to strengthen the immune system. The following review highlights the importance of fat-soluble vitamins A, D, E and K which play critical roles in maintaining immune system function and, in some cases, in preventing excessive immune activation. Therefore, a better understanding of the relevance of adequate blood levels and consequently potential supplementation strategies may contribute to the prevention and management of infectious diseases as well as better overall health of the elderly.

ß-glucans isolated from natural sources have demonstrated pluripotent immunomodulatory potential, making them a promising supportive treatment for the management of recurrent respiratory infections (RRIs) in children. This study aimed to evaluate the effects of a pleuran-based supplement (ß-glucan isolated from Pleurotus ostreatus in combination with vitamin D and zinc) on mucosal immunity -through modulating salivary secretory immunoglobulin A (sIgA) levels -in children with RRIs.

This monocentric, prospective, open-label pilot study investigated the effect of an orally administered pleuran/vitamin D/zinc supplement (1-2 chewable tablets daily depending on body weight) on the dynamics of sIgA secretion measured in saliva samples collected at three timepoints: at baseline and after 4-6 and 8-10 days.

This study included 49 children aged 6-11 years (mean age: 8.2 ± 1.6 years) with a history of one or more of the following conditions in the inclusion criteria: RRIs, allergy, and asthma. After 8-10 days with daily administration of the chewable pleuran/vitamin D/zinc supplement, children exhibited a statistically significant increase in salivary sIgA concentrations compared with baseline (227 ± 211 µg/mL; P = 0.045). No adverse events were observed during the course of the study in relation to the administration of pleuran-based supplement.

We demonstrated the beneficial effects of the short-term administration of a pleuran-based chewable supplement on mucosal immunity through increasing salivatory sIgA levels. This study confirms the favourable safety profile of this pleuran/vitamin D/zinc combination, which could be beneficial for children with acute or recurrent respiratory infections, including children with allergies and/or asthma. Moreover, the significant increases in salivary sIgA concentrations that were observed after a few days of supplementation support the use of pleuran in not only the prevention but also the treatment of acute respiratory infections.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder that represents a significant public health challenge worldwide. This multifactorial condition results from complex interactions among genetic, environmental, immune, and microbial factors. Some beneficial microbes, known as probiotics, have been identified as promising therapeutic agents for inflammatory conditions, such as IBD. In this review, we explore the potential of probiotics as a therapeutic strategy for managing IBD. Probiotics have shown promise due to their ability to modulate the gut microbiota, regulate histamine levels, and enhance vitamin D metabolism, thereby promoting a tolerant immune profile and reducing inflammation. While the exact mechanisms underlying these benefits remain incompletely understood, probiotics represent a novel and emerging approach for alleviating the exacerbated inflammation characteristic of this disorder.

Tripterygium wilfordii Hook. f. is a traditional Chinese herb that is used to treat rheumatoid arthritis (RA). Triptolide (TP), an epoxidized diterpene lactone extracted from this herb, has been suggested to be the primary active and toxic component. In this work, the material basis and molecular mechanism of toxicity induced by T. wilfordii preparations in RA were investigated. Female rats with collagen-induced arthritis were given 500 μg·kg-1 TP intragastrically or intravenously. Compared with that in the control group, the AUClast in the CIA group was 1.7-fold greater after intragastric administration, while this value decreased 22.6 % after intravenous administration, suggesting that the absorption of TP was significantly greater in the CIA group. The results from RT-PCR and probe substrate perfusion indicated that Oatp1a5 expression was upregulated while P-glycoprotein (P-gp) expression was downregulated in the duodenums of CIA rats. Naringin, an inhibitor of Oatp1a5, decreased the Peff of TP in the rat duodenum by 27.9 %, whereas verapamil hydrochloride, an inhibitor of P-gp, increased the Peff by 50.8 %, suggesting that Oatp1a5 and P-gp mediate the uptake and efflux of TP in the rat duodenum, respectively. Furthermore, among the upstream nuclear receptors, the mRNA expression levels and protein expression levels of FXR and VDR were noticeably decreased. In the present study, the absorption of TP in the duodenums of CIA rats significantly increased due to the upregulation of Oatp1a5 expression and the downregulation of P-gp expression, leading to an increase in TP plasma exposure after intragastric administration. The altered expression of Oatp1a5 and P-gp may be related to FXR and VDR.

Central precocious puberty (CPP) is an endocrine disease in children, characterized by rapid genital development and secondary sexual characteristics before the age of eight in girls and nine in boys. The premature activation of the hypothalamic-pituitary-gonadal axis (HPGA) limits the height of patients in adulthood and is associated with a higher risk of breast cancer. How to prevent and improve the prognosis of CPP is an important problem. Vitamin D receptor (VDR) is widely expressed in the reproductive system, participates in the synthesis and function of regulatory sex hormones, and affects the development and function of gonads. In addition, gut microbiota plays an important role in human health by mainly regulating metabolites, energy homeostasis, and hormone regulation. This review aims to clarify the effect of vitamin D deficiency on the occurrence and development of CPP and explore the role of gut microbiota in it. Although evidence on the interaction between vitamin D deficiency, gut microbiota, and sexual development remains limited, vitamin D supplementation and gut microbiota interventions offer a promising, non-invasive strategy for managing CPP.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by immune system dysfunction that can lead to serious health issues and mortality. Recent investigations highlight the role of gut microbiota alterations in modulating inflammation and disease severity in SLE. This review specifically summaries the variations in gut microbiota composition across various murine models of lupus. By focusing on these differences, we aim to elucidate the intricate relationship between gut microbiota dysbiosis and the development and progression of SLE in preclinical settings.

The aim of this study was to investigate the effect of dietary supplementation with 25-hydroxyvitamin D3 (25(OH)D3) on productive performance, lipid metabolism and gut microbiota in aged laying ducks. A total of 432 healthy Longyan ducks at 60-week of age were randomly allotted to 6 groups, each with 6 replicates of 12 ducks. Ducks were given a basal diet (without added 25(OH)D3) or that diet supplemented with 800, 1600, 2400, 3200, or 4000 IU/kg 25(OH)D3 for a total of 16 wk. Dietary supplementation with 25(OH)D3 improved egg production, egg mass and average daily feed intake, and decreased the feed conversion ratio (FCR) of ducks during the whole trial period (linear, quadratic; P < 0.05). Supplementation with 25(OH)D3 decreased very low-density lipoprotein (VLDL) content in yolk (P = 0.008), decreased high-density lipoprotein and low-density lipoprotein (LDL) content in plasma (P = 0.002). Hepatic index, VLDL, LDL, triglyceride and total cholesterol content in liver, nonalcoholic fatty liver activity score of liver and alanine aminotransferase activity in plasma were decreased with supplementation of 25(OH)D3 (linear or quadratic; P < 0.05). The decreased hepatic apolipoprotein B 100 and lipoprotein lipase expression, and increased hepatic peroxisome proliferator-activated receptor-α and sterol regulatory element binding protein-1 expression resulted from 25(OH)D3 supplementation (linear, quadratic; P < 0.05). Moreover, 25(OH)D3 supplementation increased the villus/crypt ratio (linear, quadratic; P < 0.05) and expression of zonula occludens protein 1 and nuclear factor-κ-gene binding in duodenum (P < 0.05). The supplementation of 25(OH)D3 reduced the abundance of Wittenberg polluted soil-2 bacteria, Synergistota, Bacteroidales, Colidextribacter, Eggerthellaceae, Oscillospira, Oscillibacter, UCG-009, Barnesiellaceae and Lachnospiraceae_UCG-010 in cecal contents (P < 0.05). Dietary requirements for 25(OH)D3 for ducks (60 to 76 wk), were estimated to be 3377 IU/kg for egg production, 3434 IU/kg for egg mass, and 3256 IU/kg for FCR. In summary, dietary 25(OH)D3 supplementation improved productive performance and influenced liver and plasma lipid homeostasis in aged laying ducks, which may be associated with the reduction of bacteria involved in carbohydrate metabolism in the cecum. Supplementing the basal diet with 3250 to 3450 IU/kg 25(OH)D3 is recommended for aged laying ducks (60 to 76 wk).

Background/Objectives: Vitamin D (VD) has immunoregulatory properties, generating interest in its potential to influence therapeutic outcomes in inflammatory bowel disease (IBD), other than affecting the expression of genes encoding enzymes and transporters involved in drug metabolism and transport. This study investigated VD-related single nucleotide polymorphisms (SNPs) as predictors of clinical responses in patients with Crohn's disease (CD) and ulcerative colitis (UC) treated with vedolizumab (VDZ) or ustekinumab (UST) after 3 (T3) and 12 months (T12), as well as the achievement of fecal calprotectin (FC) levels < 250 mg/kg, a marker of mucosal healing. Methods: In this prospective study, 103 patients (67 CD, 36 UC) were enrolled, 40 receiving VDZ and 63 receiving UST. SNPs in the genes CYP24A1, GC, CYP27B1, and VD receptor (VDR) were analyzed via polymerase chain reaction (PCR) and associated with clinical and laboratory outcomes. Results: UST therapy demonstrated a higher clinical response rate at T12 compared to VDZ (p = 0.03). A correlation was found between response at T3 and T12 (p = 0.0002). GC 1296 AC polymorphism negatively predicted response at T12, with 63.6% of non-responders carrying this genotype. CYP24A1 8620 AG was a negative predictor for achieving FC < 250 mg/kg (p = 0.045). CYP24A1 22776 CT and VDR Cdx2 GG increased the likelihood of presenting CD over UC (OR 3.40, p = 0.009 and OR 3.74, p = 0.047, respectively). Additionally, CYP27B1 -1260 GT and +2838 CT increased the likelihood of non-ileal CD (OR 3.13, p = 0.054; OR 7.02, p = 0.01). Conclusions: This study reveals associations between VD-SNPs, clinical response to VDZ and UST, and IBD phenotype and localization, supporting the development of personalized IBD treatment and warranting further validation.

The purpose of this Review was to summarize the evidence on the associations among estrogen status, cellular senescence, the gut microbiome and osteoporosis.

Indicate that osteoporosis is a global public health problem that impacts individuals and society. In postmenopausal women, a decrease in estrogen levels is associated with a decrease in gut microbial diversity and richness, as well as increased permeability of the gut barrier, which allows for low-grade inflammation. The direct effects of estrogen status on the association between bone and the gut microbiome were observed in untreated and treated ovariectomized women. In addition to the direct effects of estrogens on bone remodeling, estrogen therapy could reduce the risk of postmenopausal osteoporosis by preventing increased gut epithelial permeability, bacterial translocation and inflammaging. However, in studies comparing the gut microbiota of older women, there were no changes at the phylum level, suggesting that age-related comorbidities may have a greater impact on changes in the gut microbiota than menopausal status does. Estrogens modify bone health not only by directly influencing bone remodeling, but also indirectly by influencing the gut microbiota, gut barrier function and the resulting changes in immune system reactivity.

It was to investigate the clinical efficacy of the combination therapy of fluticasone propionate inhalation aerosol and vitamin D (VD) in pediatric bronchial asthma (BA) and analyze the correlation between serum 25-(OH)-D3 levels and immune function, as well as calcium-phosphorus metabolism. A total of 110 patients with BA were recruited. Regarding treatment plan, patients were randomly rolled into a single-drug treatment group (SDT, treated with fluticasone propionate inhalation aerosol alone) and a dual-drug treatment group (TDT, treated with the combination of fluticasone propionate inhalation aerosol and VD). The changes in serum 25-(OH)-D3 levels, immunoglobulins, T lymphocyte subsets, and inflammatory cytokine levels in children with BA under different treatment modalities were compared. Clinical symptom disappearance, asthma control, and quality of life (QoL) were assessed, and the total effective rate and adverse reactions (ARs) were compared. A control group consisting of 60 healthy children who underwent concurrent physical examinations was included. The differences in serum 25-(OH)-D3 levels, immunoglobulins, and T lymphocyte subset levels between children with BA and healthy controls were compared, and their correlations were analyzed. The TDT group showed a drastic reduction in the disappearance time of lung wheezing and dyspnea relative to the SDT group. Furthermore, the TDT group exhibited notable improvements in lung function parameters, including forced vital capacity (FVC), forced expiratory volume at one second (FEV1), FEV1/FVC, and peak expiratory flow (PEF). Blood gas analysis revealed a great decrease in PaCO2 and an increase in PaO2. The Childhood Asthma Control Test (C-ACT) scores for asthma control and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) scores for QoL showed marked increases in the TDT group. Moreover, the TDT group demonstrated notable increases in serum 25-(OH)-D3 levels, immunoglobulins (IgA, IgG, and IgM), T lymphocyte subsets (CD4+ and CD8+), as well as blood calcium and phosphorus levels. Additionally, the TDT group exhibited a prominent increase in the anti-inflammatory cytokine interleukin (IL)-10 level and a drastic decrease in the pro-inflammatory cytokines IL-6 and tumor necrosis factor alpha (TNF-alpha) levels (all P<0.05). The total effective rates of treatment in the SDT group and TDT group were 83.64 % and 96.36 %, respectively, with AR rates of 16.36 % and 7.27 %. The TDT group exhibited a superior total effective rate and an inferior incidence of ARs to the SDT group (both P<0.05). Additionally, in contrast to the control group, the BA group showed notable decreases in serum 25-(OH)-D3 levels, immunoglobulins (IgA, IgG, and IgM), T lymphocyte subsets (CD4+, CD8+, and CD4+/CD8+), as well as blood calcium and phosphorus levels (all P<0.05). Prior to treatment, there was a positive correlation between serum 25-(OH)-D3 levels and immunoglobulins (IgA, IgG, and IgM), T lymphocyte subsets (CD4+ and CD8+), as well as blood calcium and phosphorus levels in children with BA (P<0.05). In patients with BA, combined treatment with inhaled fluticasone propionate aerosol and VD may have a regulatory effect on serum 25-hydroxyVD levels, immune function, and calcium-phosphate metabolism. The correlation between serum 25-(OH)-D3 levels and immune function, as well as calcium-phosphate metabolism, suggested that VD may play a crucial role in the immune regulation and calcium-phosphate metabolism of BA.

Background/Objectives: Type II diabetes mellitus (T2DM) is recognized as a condition of mild chronic inflammation, marked by increased levels of acute-phase proteins and various inflammatory indicators. These inflammatory substances, along with inflammation of adipose tissue and the secretion of adipocytokines, can contribute to insulin resistance and β cell dysfunction. By influencing both innate and adaptive immunity, vitamin D can inhibit the production of inflammatory cytokines and help mitigate the low-grade chronic inflammation associated with T2DM. Several strategies have been proposed to increase vitamin D levels effectively and safely, but the recent and strong ones have common tactics. Short-term high doses increase the level acutely, and long-term lower doses maintain sufficient levels. Methods: The aim of our work was to determine and verify the effectiveness of high doses of vitamin D to safely increase its level in patients with type 2 diabetes mellitus, as well as the effect of these doses on selected metabolic parameters. Data from 20 studies (vitamin D group n = 612, and control group n = 592) regarding the influence of vitamin D supplementation with doses above 4000 IU on serum 25(OH)D, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), blood pressure, serum calcium, and parathormone were pooled. Results: Vitamin D supplementation significantly improved serum 25(OH)D levels, with an average increase after intervention versus baseline at 177.09%. Our studies suggest that vitamin D supplementation may benefit various parameters in T2DM patients, including glycemic control, blood pressure, and PTH levels. Conclusions: Vitamin D supplementation may have beneficial effects on various parameters in type 2 diabetes patients, including glycemic control, blood pressure, and parathormone levels. However, the results are only sometimes consistent across all studies. Further examination is needed.

Ulcerative colitis (UC) is a chronic immune-mediated inflammation of the colorectum, for which infliximab (IFX) is currently the mainstay of treatment. However, one-third of patients with UC still fail to benefit from the IFX therapy, and early exposure to IFX impairs the efficacy of other subsequent biologics. Therefore, personalized therapeutic system is urgently needed to assist in clinical decision-making and precision treatment.

Four microarray datasets of colonic biopsies from UC patients treated with IFX were obtained from the GEO database to form the Training Cohort and Validation Cohort. Differentially expressed genes (DEGs) in Training Cohort were identified and enriched for GO, KEGG and immune cell infiltration analysis. A prediction model for IFX efficacy was developed based on the LASSO and Logistic regression. The predictive accuracy of the model was verified by the Validation Cohort, and the model-genes/proteins were validated by immunohistochemistry. Gene-drug, gene-ncRNA interaction analysis were performed to identify drugs or non-coding RNAs (ncRNAs) that potentially interacted with the model-genes. Homology Modeling and Molecular Docking were conducted to filter the optimal candidate as the subsequent adjuvant or alternative for IFX in predicted non-responders. At last, the down-regulation of the key model-gene/protein CYP24A1 by the drug candidate Deferasirox was verified by Western Blot and qRT-PCR Assay based on cellular experiments.

A total of 113 DEGs were identified in the Training Cohort, mainly enriched in inflammatory cell chemotaxis, migration, and response to molecules derived from intestinal microbiota. Activated pro-inflammatory innate immune cells, including neutrophils, M1 macrophages, activated dendritic cells and mast cells, were significantly enriched in colons of non-responders. The prediction model based on three model-genes (IFI44L, CYP24A1, and RGS1) exhibited strong predictive efficacy, with AUC values of 0.901 and 0.80 in the Training and Validation Cohorts, respectively. Higher expression of the three model-genes/proteins in colons of non-responders to IFX was confirmed by clinical colonic mucosal biopsies. 4 Drugs (Calcitriol, Lunacalcipol, Deferasirox, Telaprevir), 15 miRNAs and 66 corresponding lnRNAs interacting with model-genes were identified. The protein 3D structure of the key model-gene/protein (human-derived CYP24A1) was developed. Through the Molecular Docking and cellular experimental validation, Deferasirox, which significantly down-regulated both the RNA and protein expression of CYP24A1, was identified as the optimal adjuvant or alternative for IFX in predicted non-responders with UC.

This study developed a novel prediction model for pre-assessing the efficacy of IFX in patients with UC, as the first step towards personalized therapy. Meanwhile, drugs and non-coding RNAs were provided as potential candidates to develop the next-step precise treatment for the predicted non-responders. In particular, Defeasirox appears to hold promise as an adjuvant or alternative to IFX for the optimization of UC therapy.

Vitamin D deficiency (VDD) has been found among alcoholics. However, little is known about the effect of VDD on alcoholic liver disease and the molecular mechanisms remain unclear. The aim of the current study was to evaluate whether vitamin D was deficient among patients with alcoholic fatty liver disease (AFLD) and the effect of VDD on chronic alcoholic liver injury and possible molecular mechanisms in mice. Our results found that lower 25-hydroxyvitamin D [25(OH)D] concentrations in patients with AFLD. And further analysis found that 25(OH)D is a protective factor in patients with AFLD. Mice experiments indicated that VDD can alter the composition of gut microbiota, down-regulate the protein levels of intestinal tight junction protein Occludin and E-cadherin, up-regulate the expression of inflammatory cytokines (tnf-α, il-1β, il-6, il-8, ccl2, il-10) in liver and colon tissue. And further exacerbated the protein levels of p65,P-IκB,P-p65 in alcoholic liver injury mice. In conclusion, VDD aggravates chronic alcoholic liver injury by activating NF-κB signaling pathway.

The gut microbiota plays a key role in host health. An intake of omega-3 and vitamin D3 in a separate manner is vital for maintaining good health of gut microbiota and controlling some illness manifestations. The aim of this study is to investigate the potential change in biodiversity of the gut microbiome in healthy rats supplemented with vitamin D3, omega-3 alone and their combination and to reflect onto the triglyceride levels in serum and fecal samples.

Using the 16S rRNA gene Miseq Illumina NGS, and monitoring triglyceride levels in serum and fecal samples coupled with several clinical parameters, we examined the effect of orally taken combination of omega-3 and vitamin D3 alongside the separate intake of supplements on gut microbiota in 24 healthy white Wistar rats for six weeks. The study findings showed that combination treatment encouraged the growth of opportunistic Clostridia class during day 21 and 42 of treatment by 7.7 and 7.4 folds, respectively, exhibited incomplete absorption levels for both supplements when used concomitantly, demonstrated a damaging effect on the gut intestinal lining wall thickness (126 µm) when compared to control group (158  µm), increasing lumen diameter (400 µm), and showed higher triglyceride level in fecal samples.

These findings indicate that omega-3 and vitamin D3 supplements as combination intake reveal unfavorable effects, thus, it is advised to conduct further in-depth studies to clarify the presence or absence of any chemical interaction between both supplements' molecules and to investigate based on human model to attain a superior perspective.

There is a growing body of evidence suggesting that the composition of intestinal flora plays a significant role in regulating lipid metabolism. 2', 3', 5'-tri-O-acetyl-N6-(3-hydroxyphenyl) adenosine (IMMH007) is a new candidate compound for regulating blood cholesterol and other lipids. In this study, we conducted metagenomic and metabolomic analyses on samples from high-fat diet-fed (HFD) hamsters treated with IMMH007. Our findings revealed that IMM-H007 reversed the imbalance of gut microbiota caused by a high-fat diet. Additionally, it activated adiponectin receptor and pantothenate and CoA biosynthesis pathway-related genes, which are known to regulate lipid and glucose metabolism. Furthermore, IMM-H007 promotes cholesterol metabolism by reducing the abundance of genes and species associated with 7α-dehydroxylation and bile salt hydrolase (BSH). Metabolomics and pharmacological studies have shown that IMM-H007 effectively improved glucose and lipid metabolism disorders caused by HFD, reduced the aggregation of secondary bile acids (SBAs), significantly increased the content of hyodeoxycholic acid (HDCA), and also activated the expression of VDR in the small intestine. As a result, there was a reduction in the leakage of diamine oxidase (DAO) into the bloodstream in hamsters, accompanied by an upregulation of ZO-1 expression in the small intestine. The results suggested that IMM-H007 regulated glucose and lipid metabolism, promoted cholesterol metabolism through activating the expression of VDR, inhibiting inflammatory and improving the permeability of the intestinal barrier. Thus, our study provides new understanding of how IMM-H007 interacts with intestinal function, microbiota, and relevant targets, shedding light on its mechanism of action.

Severe burn patients frequently suffer from 1,25-Dihydroxyvitamin D3 (1,25-[OH]2-D3) deficiency. In this study, we investigated the effect of 1,25-[OH]2-D3 on early mortality post severe burn and potential underlying mechanisms. Our results indicate that 1,25-[OH]2-D3 significantly reduced early mortality in mice post severe burn injury. A decrease in serum lipopolysaccharide levels and an increase in serum superoxide dismutase activity were found after administration of 1,25-[OH]2-D3. Furthermore, 1,25-[OH]2-D3 demonstrated protective effects on both intestinal and lung histology and ameliorated lung inflammation. Its anti-inflammatory effect was further confirmed in airway epithelial cells. In conclusion, our study provides evidence that 1,25-[OH]2-D3 has a significant impact on the reduction of early mortality post severe burn injury, possibly through its ability to alleviate endotoxemia, oxidative stress, and inflammation. Our findings highlight the potential of 1,25-[OH]2-D3 to protect the intestinal mucosal barrier in the early stage following major burn injury and opens up new avenues for clinical application of 1,25-[OH]2-D3 in burn patients.

Vitamin D3 (25-hydroxyvitamin D3 (VD)) and vitamin E (VE) have proven to have immunomodulatory and antioxidant functions along with capacities to improve the reproductive function in chickens. Coccidiosis in laying hens at different stages of growth has been shown to negatively affect performance, immune response, and oxidative status, thus increasing the cost of production. A study was conducted to evaluate the influence of dietary VD or VE on performance, gut health, immune response, and oxidative status of laying hens at peak production. Laying hens (23 wk-of-age, n = 225) were randomly allocated into 5 treatment groups (n = 9 hens/replicate) with 5 replicate groups each: 1) unchallenged control (UC), 2) pair-fed control (PF), 3) challenged control (CC), 4) challenged control top-dressed with 5,000 IU of 25-hydroxyvitamin D3 (VD) per kg of diet, and 5) challenged control top-dressed with 100 IU of DL-α-tocopherol (VE). At 25 wk-of-age, hens grouped in CC, VD, and VE were challenged with mixed Eimeria spp. to induce coccidiosis. VD or VE supplemented hens did not impact bird body weight; however, egg production increased by 10.36% and 13.77%, respectively (P < 0.0001). Furthermore, the gut health of the hens was improved with either VD or VE supplementation, as indicated by lowered gut permeability and intestinal lesion scores (P < 0.05). VE significantly reduced the heterophil count (P = 0.0490) alongside numerically increasing the peripheral CD4+ and CD8+ T cells and monocyte counts (P > 0.05). Both VD or VE increased the TAC at 14 DPI compared to UC (P<0.05). Preliminary findings suggest that dietary VD or VE supplementation has the potential to improve gut health, modulate the immune response, and increase egg production in coccidiosis-infected laying hens.

This study evaluated the therapeutic efficacy and underlying mechanisms of crisaborole combined with vitamin D in the treatment of allergic contact dermatitis. While crisaborole, a phosphodiesterase 4 inhibitor, and vitamin D analogs are commonly used in the treatment of atopic dermatitis, their combined therapeutic potential in allergic contact dermatitis (ACD) remains unexplored. Given their anti-inflammatory properties, we hypothesized that the combination of crisaborole and vitamin D could offer superior efficacy in mitigating the symptoms and underlying mechanisms of allergic contact dermatitis. In vitro, HaCaT cells stimulated with tumor necrosis factor-α and interferon-γ were treated with a combination of crisaborole and vitamin D, followed by cytokine expression analysis. In vivo, male C57BL/6 mice were divided into five groups and treated accordingly: blank control, dinitrochlorobenzene-induced model, crisaborole alone, vitamin D alone, and a combination of crisaborole and vitamin D. On day 14, dorsal skin and ear thickness were measured, followed by comprehensive pathological evaluations. In vivo and in vitro experiments showed that the expression levels of inflammatory factors were significantly lower in the DNCB + VD + Cri group than in the DNCB group. Histological analyses revealed that, compared with the DNCB group, the combined treatment group significantly reduced epidermal hyperkeratosis, improved epidermal transdermal water loss, decreased dermatitis scores, and diminished mast cell infiltration. Moreover, it lowered the expression levels of IL-6, IL-4, TNF-α, iNOS, IL-17, CC chemokine ligand 2 (CCL2), and CC chemokine receptor 2 (CCR2). CCL2 recognizes CCR2 and stimulates inflammatory cells, enhancing the inflammatory response. Increased CCL2 expression correlates with heightened inflammation and dendritic cell infiltration in ACD, while downregulation of CCL2 attenuates inflammation. Thus, the combined use of crisaborole and vitamin D demonstrates superior therapeutic efficacy over monotherapy in a mouse model of ACD. The combination of vitamin D and crisaborole significantly reduces inflammation and epidermal hyperkeratosis in a mouse model of allergic contact dermatitis, demonstrating superior therapeutic efficacy compared to either treatment alone. This suggests that the combined therapy could be a promising approach for the prevention and treatment of allergic contact dermatitis.

Food allergy, referred to as the atypical physiological overreaction of the immune system after exposure to specific food components, is considered one of the major concerns in food safety. The prevalence of this emerging worldwide problem has been increasing during the last decades, especially in industrialized countries, being estimated to affect 6-8% of young children and about 2-4% of adults. Marine organisms are an important source of bioactive substances with the potential to functionally improve the immune system, reduce food allergy sensitization and development, and even have an anti-allergic action in food allergy. The present investigation aims to be a comprehensive report of marine bioactive compounds with verified actions to improve food allergy and identified mechanisms of actions rather than be an exhaustive compilation of all investigations searching beneficial effects of marine compounds in FA. Particularly, this research highlights the capacity of bioactive components extracted from marine microbial, animal, algae, and microalgae sources, such as n-3 long-chain polyunsaturated fatty acids (LC-PUFA), polysaccharide, oligosaccharide, chondroitin, vitamin D, peptides, pigments, and polyphenols, to regulate the immune system, epigenetic regulation, inflammation, and gut dysbiosis that are essential factors in the sensitization and effector phases of food allergy. In conclusion, the marine ecosystem is an excellent source to provide foods with the capacity to improve the hypersensitivity induced against specific food allergens and also bioactive compounds with a potential pharmacological aptitude to be applied as anti-allergenic in food allergy.

Vitamin D/Vitamin D receptor (VD/VDR) signaling and the Notch pathway are involved in intestinal barrier restoration in colitis; however, their relationship and underlying mechanism are largely unknown. Therefore, this study aimed to investigate the role and mechanism of VD/VDR and the Notch pathways in intestinal barrier protection.

Genetic Vdr knockout (VDR KO) and VD deficient (VDd) mice were established, and colitis was induced by feeding 2.5% dextran sodium sulfate (DSS) water. Mechanistic studies, including real-time PCR, immunofluorescence, Western blotting and dual-luciferase reporter assays, were performed on cultured Caco-2 cells and intestinal organoids.

VD deficiency and VDR genetical KO increased the severity of DSS-induced colitis in mice, which presented a higher disease activity index score, increased intestinal permeability, and more severe intestinal histological damage than controls, accompanied by decreased and disrupted claudin-1 and claudin-3. Moreover, inhibition of Notch pathway by LY411,575 aggravated the severity of DSS-induced colitis and intestinal injury. In Caco-2 cells and intestinal organoids, the expression of Notch-1, N1ICD and Hes1 decreased upon downregulation or KO of VDR but increased upon paricalcitol (PAR, a VDR agonist) treatment. Meanwhile, PAR rescued claudin-1 and claudin-3 impairments that resulted from TNF-α exposure but failed to restore claudin-3 upon Notch inhibition. The dual-luciferase reporter assay further suggested that VD/VDR positively regulated the Notch signaling pathway by modulating Notch-1 transcription.

VD/VDR positively modulates Notch activation by promoting Notch-1 transcription to maintain intestinal tight junction integrity and barrier function. This highlights the VD/VDR-Notch pathway as a potential new therapeutic target for protecting the intestinal barrier against ulcerative colitis.

Natural Health Products (NHPs) have long been considered a valuable therapeutic approach for the prevention and treatment of various diseases, including cancer. However, research on this topic has led to inconclusive and often controversial results. This review aims to provide a comprehensive update of the effects and mechanisms related to the use of NHPs, to describe the results of randomized clinical trials (RCTs) on their effects in cancer patients, and to critically discuss factors influencing clinical outcomes. RCTs available in the literature, even those studying the same NHP, are very heterogeneous in terms of indications, doses, route and timing of administration, and outcomes evaluated. Silymarin, ginsenoside, and vitamin E appear to be useful in attenuating adverse events related to radiotherapy or chemotherapy, and curcumin and lycopene might provide some benefit in patients with prostate cancer. Most RCTs have not clarified whether NHP supplementation provides any real benefit, while harmful effects have been shown in some cases. Overall, the available data suggest that although there is some evidence to support the benefits of NHPs in the management of cancer patients, further clinical trials with the same design are needed before their introduction into clinical practice can be considered.

Vitamin D deficiency is common in patients with inflammatory bowel disease (IBD). In this study, we aimed to evaluate the prevalence and risk factors of vitamin D deficiency in a Taiwanese IBD cohort. Vitamin D levels were checked in adult patients with IBD who were treated at Changhua Christian Hospital, a medical center in central Taiwan, from January 2017 to December 2023. The risk factors for vitamin D deficiency were evaluated. 106 adult IBD patients were included, including 20 patients with Crohn's disease and 86 with ulcerative colitis. The median age at diagnosis was 39.2 years. The mean vitamin D level was 22.2 ± 8 ng/mL. Forty-five patients (42.5%) had vitamin D deficiency (vitamin D level < 20 ng/mL). Comparing patients with normal vitamin D levels and those with vitamin D deficiency after multivariate adjustment, female sex and early age at diagnosis were identified as statistically significant risk factors. We found a prevalence of 42.5% of vitamin D deficiency in the Taiwanese IBD population. Understanding this issue is essential for teaching patients and doctors about vitamin D deficiency screening and improving patient outcomes.

Colorectal cancer (CRC) is one of the most common cancers diagnosed in the world. Although environmental and genetic factors play a major role in the pathogenesis of CRC, extensive research has suggested that vitamin D may play a pivotal role in the development of CRC. Vitamin D, primarily obtained through sunlight exposure, dietary sources, and supplements, has long been recognized for its essential functions in maintaining health, including immune regulation. This article delves into the intricate relationship between vitamin D, the immune system, gut flora, and the prevention of CRC. It presents a synthesis of epidemiological data, experimental studies, and clinical trials, highlighting the mechanisms by which vitamin D influences immune cell function, cytokine production, and inflammation. By enhancing the immune system's surveillance and anti-tumor activity, vitamin D may offer a promising avenue for CRC prevention. Furthermore, this comprehensive review delves into the prospective clinical applications of vitamin D supplementation and delineates the forthcoming avenues of research in this dynamic domain. Additionally, the paper tentatively outlines a spectrum of prophylactic impacts of vitamin D on CRC, emphasizing its significant potential in reducing CRC risk through shedding light on its mechanisms, encompassing antineoplastic mechanisms, influences on the immune system, and modulation of the gut microbiome.

Recently, Serum vitamin D (Vit. D) levels evaluation and the use of Vit. D supplements have increased substantially. There is no specific guideline for the duration of Vit. D supplementation, so yet Vit. D supplementation duration has remained a critical and controversial issue. This study aimed to determine the vit. D supplementation duration to reach an adequate or optimal Vit. D status and its effect on lipid profile.

In this longitudinal study, 345 women with different status of Vit. D levels were enrolled and followed up for one year. Eligible participants received 50,000 IU Vit. D3 (cholecalciferol) once a month for 12 consecutive months. The serum Vit. D levels and lipid profiles were measured at baseline, 3rd, 6th, and 12th months after the intervention. Participants were categorized based on Vit. D level at baseline into deficiency (< 20 ng/mL), inadequate (20-30 ng/mL), and adequate (> 30 ng/mL) groups, and the data were compared at different times between the three groups.

Three deficiency (n = 73), inadequate (n = 138) and adequate (n = 134) groups of participants were followed. In all participants the average amount of Vit. D level changes were 8 ng/mL after one year of supplementation. The mean changes of serum Vit. D level in 6th and 12th months vs. 3th month was as below: In deficiency group: 4.08 ± 0.85 and 10.01 ± 1.02 ng/mL; (p < 0.001), in inadequate group: 3.07 ± 0.59 and 7.26 ± 0.78 ng/mL; (p = 0.001) and in adequate group: 2.02 ± 0.88 and 6.44 ± 1.005 ng/ml; (p = 0.001). Lipid profiles were improved in three groups. So, the mean changes of lipid profiles at the end of the study comparing with the baseline were: -5.86 ± 2.09, -7.22 ± 1.43 and - 6.17 ± 1.72 (mg/dl) for LDL (p < 0.05); -12.24 ± 3.08, -13.64 ± 3.21 and - 17.81 ± 2.94 (mg/dl) for cholesterol (p < 0.05) in deficiency, inadequate and adequate groups, respectively. For triglyceride, the mean changes were - 13.24 ± 5.78 and - 15.85 ± 7.49 (mg/dl) in deficiency and adequate groups, respectively (p < 0.05). Although the triglyceride decreased in the inadequate group at the end of the study but this difference was not significant (p = 0.67).

Taking of 50,000 IU Vit. D 3 monthly for 12 months resulted in reaching its level to adequate level in both deficiency and insufficient groups; however, in the adequate group its level did not reach above than 50 ng/mL. Therefore, 50,000 IU Vit. D3 supplementation monthly for one year can have beneficial effects on lipid profiles and there is no risk of toxicity in healthy women.

Inflammatory bowel diseases (IBDs) are characterized by chronic gastrointestinal inflammation due to abnormal immune responses to gut microflora. The gut-brain axis is disrupted in IBDs, leading to neurobiological imbalances and affective symptoms. Systemic inflammation in IBDs affects the brain's inflammatory response system, hormonal axis, and blood-brain barrier integrity, influencing the gut microbiota. This review aims to explore the association between dysregulations in the gut-brain axis, serum biomarkers, and the development of cognitive disorders. Studies suggest a potential association between IBDs and the development of neurodegeneration. The mechanisms include systemic inflammation, nutritional deficiency, GBA dysfunction, and the effect of genetics and comorbidities. The objective is to identify potential correlations and propose future research directions to understand the impact of altered microbiomes and intestinal barrier functions on neurodegeneration. Serum levels of vitamins, inflammatory and neuronal damage biomarkers, and neuronal growth factors have been investigated for their potential to predict the development of neurodegenerative diseases, but current results are inconclusive and require more studies.

Cancer patients face increased susceptibility to invasive infections, primarily due to ulcerative lesions on mucosal surfaces and immune suppression resulting from chemotherapy. Pseudomonas aeruginosa (P. aeruginosa) bacteremia is notorious for its rapid progression into fatal sepsis, posing a significant threat to cancer patients, particularly those experiencing chemotherapy-induced neutropenia. This bacterial infection contributes significantly to morbidity and mortality rates among such individuals. Our latest report showed the mutually beneficial effects of postbiotic butyrate on 1,25-dihydroxyvitamin D3 (1,25D3)-controlled innate immunity during Salmonella colitis. Hence, we investigated the impact of butyrate and 1,25D3 on chemotherapy-induced gut-derived P. aeruginosa sepsis in mice. The chemotherapy-induced gut-derived P. aeruginosa sepsis model was established through oral administration of 1 × 107 CFU of the P. aeruginosa wild-type strain PAO1 in C57BL/6 mice undergoing chemotherapy. Throughout the infection process, mice were orally administered butyrate and/or 1,25D3. Our observations revealed that the combined action of butyrate and 1,25D3 led to a reduction in the severity of colitis and the invasion of P. aeruginosa into the liver and spleen of the mice. This reduction was attributed to an enhancement in the expression of defensive cytokines and antimicrobial peptides within the cecum, coupled with decreased levels of zonulin and claudin-2 proteins in the mucosal lining. These effects were notably more pronounced when compared to treatments administered individually. This study unveils a promising alternative therapy that involves combining postbiotics and 1,25D3 for treating chemotherapy-induced gut-derived P. aeruginosa sepsis.

In observational studies, the 25-hydroxyvitamin D (25(OH)D) level in body has been found to be closely related to particulate matter (PM) air pollution. In this study, we used the two-sample mendelian randomisation (MR) method to investigate and discuss the potential causal relationship and mode of influence.

MR study.

PM data (PM10, PM2.5-10, PM2.5, PM2.5 absorbance) came from the UK Biobank database, and 25(OH)D data came from European Bioinformatics Institute (EBI) database. The analysis was conducted utilising three prominent methods (inverse-variance-weighted [IVW], MR-Egger, weighted median, weighted mode, and simple mode). The primary emphasis was placed on IVW, accompanied by heterogeneity and horizontal pleiotropy tests. Furthermore, sensitivity analysis was undertaken.

The MR analysis revealed a significant association between exposure to PM10 and a decrease in levels of 25(OH)D (odds ratio [OR]: 0.878, 95% confidence interval [CI]: 0.789-0.977). However, no significant relationship was observed between PM2.5 exposure and 25(OH)D (OR: 0.943, 95%CI: 0.858-1.037). Further analysis indicated that the main contributor to the decline in 25(OH)D levels is linked to PM2.5-10 exposure (OR: 0.840, 95%CI: 0.751-0.940) and PM2.5 absorbance (OR: 0.875, 95%CI: 0.824-0.929). No heterogeneity and horizontal pleiotropy existed.

The MR results suggest that PM (PM10, PM2.5-10 and PM2.5 absorbance) exposure lowers vitamin D (VD) levels, but PM2.5 was not found to have a significant effect on VD in humans.

Multiple factors, such as dietary patterns, pharmaceutical interventions, and exposure to harmful substances, possess the capacity to influence gut microbiota composition. Gut microbiota dysbiosis has emerged as a significant contributor to the progression of chronic kidney disease (CKD) and its associated complications. By comprehending the intricacies of the intestinal microbiota, this research endeavor holds the potential to offer novel perspectives on potential strategies for mitigating CKD progression.

In this retrospective analysis, we assessed gut microbiota composition in CKD patients. Fecal samples were collected from a cohort of 44 patients with stage 3-4 CKD, alongside a control group consisting of 132 healthy volunteers. Subsequently, 16 s rDNA sequencing was conducted to examine the composition of the gut microbiota.

Our findings revealed significant alterations in the diversity of intestinal microbiota in fecal samples between patients with stage 3-4 CKD and healthy subjects. Among the 475 bacterial genera, 164 were shared, while 242 dominant genera were exclusive to healthy subjects and 69 to CKD stages 3-4 samples. Notably, healthy volunteers exhibited a prevalence of intestinal Firmicutes and Bacteroidetes, whereas stage 3-4 CKD patients displayed higher abundance of Proteobacteria and Actinobacteria. The presence of uncultured Coprobacillus sp. notably contributed to distinguishing between the two groups. ROC curve analysis identified distinct microbiota with superior diagnostic efficacy for discriminating stage 3-4 CKD patients from healthy individuals. Metabolic pathway analysis revealed differing dominant pathways between the two groups-the NADH dehydrogenase pathway in healthy individuals and the phosphate acetyltransferase pathway in stage 3-4 CKD patients. Moreover, the CKD cohort displayed a higher proportion of Gram-negative bacteria and facultative anaerobes.

In conclusion, our study underscores the profound influence of gut microbiota dysbiosis on CKD progression. The distinct microbial profiles observed in CKD patients highlight the potential efficacy of microbiota-based interventions in mitigating CKD advancement.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent condition characterized by abnormal fat accumulation in the liver, often associated with metabolic disorders. Emerging evidence suggests a potential link between vitamin D deficiency and the development and progression of MASLD. The current review provides a concise overview of recent studies uncovering novel mechanistic insights into the interplay between vitamin D and MASLD. Several epidemiological studies have highlighted a significant association between low vitamin D levels and an increased risk of MASLD. Vitamin D, traditionally known for its role in bone health, has now been recognized as a key player in various physiological processes, including immune regulation and inflammation. Experimental studies using animal models have demonstrated that vitamin D deficiency exacerbates liver steatosis and inflammation, suggesting a potential protective role against MASLD. Mechanistically, vitamin D appears to modulate MASLD through multiple pathways. Firstly, the vitamin D receptor (VDR) is abundantly expressed in liver cells, indicating a direct regulatory role in hepatic function. Activation of the VDR has been shown to suppress hepatic lipid accumulation and inflammation, providing a mechanistic basis for the observed protective effects. Additionally, vitamin D influences insulin sensitivity, a critical factor in MASLD pathogenesis. Improved insulin sensitivity may mitigate the excessive accumulation of fat in the liver, thus attenuating MASLD progression. In parallel, vitamin D exhibits anti-inflammatory properties by inhibiting pro-inflammatory cytokines implicated in MASLD pathophysiology. Experimental evidence suggests that the immunomodulatory effects of vitamin D extend to the liver, reducing inflammation and oxidative stress, key drivers of MASLD, and the likelihood of hepatocyte injury and fibrosis. Understanding the complex interplay between vitamin D and MASLD provides a basis for exploring targeted therapeutic strategies and preventive interventions. As vitamin D deficiency is a modifiable risk factor, addressing this nutritional concern may prove beneficial in mitigating the burden of MASLD and associated metabolic disorders.