Obesity is an important risk factor for incidence and death for many types of cancer. Vitamin D reduces risk of incidence and death for many types of cancer. This review outlines the mechanisms by which obesity increases risk of cancer, how vitamin D reduces risk of cancer, and the extent to which vitamin D counters the effects of obesity in cancer. Vitamin D is a partial ally against some of obesity's pro-carcinogenic effects, notably by reducing inflammation and regulating sex hormone receptors, leptin resistance, cellular energy metabolism, the microbiome, and hypoxia. However, it can act stronger in against the renin-angiotensin system, insulin resistance, and oxidative stress in cancer. Additionally, excess fat tissue sequesters vitamin D and, along with its dilution in increased body volume, further reduces its bioavailability and serum concentration, limiting its protective effects against cancer. In conclusion, while vitamin D cannot reverse obesity, it plays a significant role in mitigating its pro-carcinogenic effects by targeting several mechanisms.

It is known that microbiome and health are related, in addition, recent research has found that microbiome has potential clinical uses. These facts highlight the importance of the microbiome in actual science. However, microbiome data has some characteristics that makes its statistical study challenging. In recent years, longitudinal and non-longitudinal methods have been designed to analyze the microbiota and knowing more about the bacterial behavior. In this article in the form of a review we summarize the characteristics of microbiome data and the statistical methods most widespread to analyze it. We have taken into account if the strategies are longitudinal or not. We also classify the methods based on their specific analytical objectives and based on their mathematical characteristics. The methods are structured according to their biological goals and mathematical features, ensuring that the insights provided are both relevant and accessible to professionals in biology and statistics. We present this review as a reference for the most widely used methods in microbiome data analysis and as a foundation for identifying potential areas for future research. We want to point out that this review can be particularly useful to remark the importance of the methodology designed in order to study microbiome longitudinal datasets.

Immunosenescence is the loss and change of immunological organs, as well as innate and adaptive immune dysfunction with ageing, which can lead to increased sensitivity to infections, age-related diseases, and cancer. Emerging evidence highlights the role of gut-vitamin D axis in the regulation of immune ageing, influencing chronic inflammation and systemic health. This review aims to explore the interplay between the gut microbiota and vitamin D in mitigating immunosenescence and preventing against chronic inflammation and age-related diseases.

Gut microbiota dysbiosis and vitamin D insufficiency accelerate immunosenescence and risk of chronic diseases. Literature data reveal that vitamin D modulates gut microbiota diversity and composition, enhances immune resilience, and reduce systemic inflammation. Conversely, gut microbiota influences vitamin D metabolism to promote the synthesis of active vitamin D metabolites with implications for immune health.

These findings underscore the potential of targeting gut-vitamin D axis to modulate immune responses, delay the immune ageing, and mitigate age-related diseases. Further research is needed to integrate vitamin D supplementation and microbiome modulation into strategies aimed at promoting healthy ageing.

Oral eubiosis is of utmost importance for local and systemic health. Consolidated habits, as excessive alcohol consumption, smoke, inappropriate oral hygiene, and western diet, exert detrimental effects on oral microbiota composition and function. This leads to caries, gingivitis, and periodontitis, also increasing the risk of preterm births, inflammation, and cancer. Thus, effective tools to contain pathobiont overgrowth and virulence and restore oral eubiosis are needed. Therefore, the effects of Limosilactobacillus reuteri LRE11, Lacticaseibacillus rhamnosus LR04, Lacticaseibacillus casei LC04, and their co-culture cell-free supernatants (CFSs), produced in both conventional MRS medium and a novel animal derivative-free medium named TIL, along with vitamin D, were assessed on the viability and interleukin (IL)-6 production of oral epithelial FaDu cells infected with Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, and Porphyromonas gingivalis. The CFS proteomic, short chain fatty acid, and lactic acid contents were also investigated. Interestingly, probiotic CFSs and vitamin D differentially reduced the infected cell IL-6 production and counteracted the infection-induced cytotoxicity. Taken together, these results suggest that probiotics and vitamin D can reverse pathogen-induced cell damage. Since probiotic CFS effect is both strain and growth medium composition dependent, further experiments are required to deepen the probiotic and vitamin D synergic activity in this context.

Preeclampsia (PE) is a pregnancy-specific multisystem disorder and a leading cause of maternal and perinatal mortality globally. Despite numerous studies highlighting the potential roles of gut microbiota, anandamide (AEA), and Vitamin D (VitD) in PE, none have established them as reliable biomarkers for predicting disease onset. Moreover, their interactions in late-stage pregnancy women remain poorly understood.

Thirty-four preeclamptic patients (called PE group) and thirty-nine matched healthy late-pregnant women (called LP group) were involved in this case-control study. Fecal samples, which were used to acquire the diversity and composition of gut microbiota, were analyzed by 16S rRNA gene sequencing. Plasma AEA concentrations and serum VitD levels were determined by high-performance liquid chromatography-mass spectrometry (HPLC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), respectively.

In this study, β diversity but not α diversity significantly differed between the LP and PE groups. Compared with the LP group, the relative abundances of Prevotella, Erysipelotrichaceae_UCG-003, and Dorea were increased dramatically in the PE group, whereas the relative abundances of Subdoligranulum, Parabacteroides, Bacteroides were significantly decreased in the PE group. Furthermore, women with PE had a substantially lower plasma level of AEA and a marked decrease in serum VitD compared to normal late-pregnant women. Lastly, although the serum level of AEA was not significantly correlated with VitD or any of the top 6 marker genera, VitD was significantly negatively correlated with the relative abundance of Dorea, a novel finding in this context.

The gut microbiota profile of the PE group was significantly different from that of the LP group. Although no significant correlations were identified between the plasma AEA levels and serum VitD levels or any of the top 6 identified marker genera, a significant negative correlation was observed between VitD and Dorea, indicating VitD and gut microbiota have the potential to be combined targets for early diagnosis and management of PE.

Osteoarthritis (OA) is one of the most common degenerative diseases, and the number of patients has been constantly increasing. Non-steroidal anti-inflammatory drugs, glucocorticosteroids, opioids, etc., and surgical procedures, e.g. arthroplasty, are among the most common methods of treatment. There are reasons to believe that the gut microbiome (GMB) may influence inflammatory processes occurring in the pathomechanism of OA. The inflammatory processes occurring in the intestines may lead to disruption of tight junctions and increased concentrations of pro-inflammatory cytokines, resulting in increased permeability of intestines, causing low-grade inflammation, including in the joints. Methods of altering the GMB composition to reduce the inflammatory and joint degenerative processes are known only to some extent, and long-term research is required. Osteoarthritis, a particularly well-known and very widespread disease due to the aging population, is characterized by moderate and local inflammation. It occurs due to the effects of biomechanical cartilage wear with damage of joint structures, primarily through degenerative processes. OA represents a therapeutic challenge, and any element that can influence its inhibition is highly sought after. Therefore, these methods seem to offer a promising additional approach to treatment.

Background: Chronic stress and chronic pain are closely linked by the capacity to exacerbate each other, sharing common roots in the brain and in the gut. The strict intersection between these two neurological diseases makes important to have a therapeutic strategy aimed at preventing both to maintain mental health in patients. Diet is an modifiable lifestyle factor associated with gut-brain axis diseases and there is growing interest in its use as adjuvant to main therapies. Several evidence attest the impact of specific diets or nutrients on chronic stress-related disorders and pain with a good degree of certainty. A daily adequate intake of foods containing micronutrients such as amino acids, minerals and vitamins, as well as the reduction in the consumption of processed food products can have a positive impact on microbiota and gut health. Many nutrients are endowed of prebiotic, anti-inflammatory, immunomodulatory and neuroprotective potential which make them useful tools helping the management of chronic stress and pain in patients. Dietary regimes, as intermittent fasting or caloric restriction, are promising, although further studies are needed to optimize protocols according to patient's medical history, age and sex. Moreover, by supporting gut microbiota health with diet is possible to attenuate comorbidities such as obesity, gastrointestinal dysfunction and mood disorders, thus reducing healthcare costs related to chronic stress or pain.Objective: This review summarize the most recent evidence on the microbiota-mediated beneficial effects of macro- and micronutrients, dietary-related factors, specific nutritional regimens and dietary intervention on these pathological conditions.

The intestine is populated by a complex and dynamic assortment of microbes, collectively called gut microbiota, that interact with the host and contribute to its metabolism and physiology. Diet is considered a key regulator of intestinal microbiota, as ingested nutrients interact with and shape the resident microbiota composition. Furthermore, recent studies underscore the interplay of dietary and microbiota-derived nutrients, which directly impinge on intestinal stem cells regulating their turnover to ensure a healthy gut barrier. Although advanced sequencing methodologies have allowed the characterization of the human gut microbiome, mechanistic studies assessing diet-microbiota-host interactions depend on the use of genetically tractable models, such as Drosophila melanogaster. In this review, we first discuss the similarities between the human and fly intestines and then we focus on the effects of diet and microbiota on nutrient-sensing signaling cascades controlling intestinal stem cell self-renewal and differentiation, as well as disease. Finally, we underline the use of the Drosophila model in assessing the role of microbiota in gut-related pathologies and in understanding the mechanisms that mediate different whole-body manifestations of gut dysfunction.

The incidence of vitamin D deficiency among pregnant women remains high and is associated with vitamin D deficiency in infants. In normally breastfed infants, Bifidobacteriaceae and Lactobacillaceae are known to help in maintaining immunotolerance and prevent infection. Vitamin D in the gastrointestinal tract plays a role in determining the composition and function of intestinal bacteria. Preterm infants are vulnerable to intestinal dysbiosis and sepsis due to bacterial translocation. This study aimed to determine the association between vitamin D levels and intestinal dysbiosis.

It was a cohort study conducted in the Neonatal Unit, Cipto Mangunkusumo Hospital, Tertiary hospital in Indonesia, from November 2019 to January 2021. The inclusion criteria in this study were preterm infants with a gestational age of less than 32 weeks or a birth weight of less than 1500 g. Total 25-hydroxyvitamin D (25(OH)D) levels were collected from the umbilical cords of very preterm or very low birth weight infants. A fecal examination was performed on the seventh day of life to assess intestinal bacteria using real-time PCR for four bacterial genera: Bifidobacteriaceae, Lactobacillaceae, Enterobacteriaceae, and Clostridiaceae.

A total of 43 infants were included in this study. Among the subjects, 53.4% had vitamin D deficiency. There was no association identified between vitamin D deficiency and intestinal dysbiosis (RR 0.67; 95% CI (0.15-2.82), p-value = 0.531). However, the ratio of Lactobacillacecae to Enterobacteriaceae was lower in those with vitamin D deficiency.

Vitamin D deficiency was not associated with dysbiosis in preterm infants. However, this study found that the ratio of Lactobacillaceae to Enterobacteriaceae in those with vitamin D deficiency was lower than in those without vitamin D deficiency. Further research is warranted to confirm this finding.

The VDR gene is identified as a crucial host factor, influencing the gut microbiota. The current research focuses on an observational study that compares gut microbiota composition among individuals with different VDR gene TaqI polymorphisms in a Caucasian Spanish population. This study aims to elucidate the interplay between genetic variations in the VDR gene and the gut microbial composition.

87 healthy participants (57 men, 30 women), aged 18 to 48 years, were examined. Anthropometric measures, body composition, and dietary habits were assessed. VDR gene polymorphism TaqI rs731236 was determined using TaqMan assays. The V3 and V4 regions of the 16S rRNA gene were sequenced to study bacterial composition, which was analyzed using QIIME2, DADA2 plugin, and PICRUSt2. Statistical analyses included tests for normal distribution, alpha/beta diversity, ADONIS, LEfSe, and DESeq2, with established significance thresholds.

No significant differences in body composition or dietary habits were observed based on VDR genotypes. Dietary intake analysis revealed no variations in energy, macronutrients, or fiber among the different VDR genotypes. Fecal microbiota analysis indicated significant differences in alpha diversity as measured by Faith's Phylogenetic Diversity index. Differential abundance analysis identified taxonomic disparities, notably in the genera Parabacteroides and Butyricimonas.

Overall, this study suggests potential associations between genetic variations in the VDR gene and the composition and function of gut microbiota.

Irritable bowel syndrome (IBS) is a common disease with unknown etiology. Poor dietary intake with nutritional deficiency and overweight have been described to increase the risk of IBS. The aim of the present study was to compare weight and circulating levels of micronutrients in IBS compared with healthy controls.

Cross-sectional study.

Patients diagnosed with IBS and healthy volunteers were recruited. Participants had to complete a dietary diary book and the questionnaires Rome IV, IBS-severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS). Weight and height were measured, and blood samples were drawn. C-reactive protein (CRP), cobalamin, folate, iron, total iron-binding capacity (TIBC), and 25-hydroxy (25-OH) vitamin D were analyzed. Differences were calculated between groups and generalized linear model for regressions was adjusted for false discovery rate (FDR).

IBS patients (n = 260) were elder than controls (n = 50) (44.00 (33.25-56.00) vs. 37.85 (30.18-45.48) years; p = 0.012). After adjustment for age, both weight (β: 5.880; 95% CI: 1.433-10.327; p = 0.010, FDR = 0.020) and body mass index (BMI) (β: 2.02; 95% CI: 0.68-3.36; p = 0.003, FDR = 0.012) were higher in patients. Among IBS participants, 48.1% were overweight/obese compared with 26.0% in controls (p = 0.007). Diarrhea-predominated IBS had highest weight (p < 0.001) and BMI (p = 0.077). CRP and cobalamin were higher in patients than controls (p = 0.010 vs. p = 0.007), whereas folate was highest in controls (p = 0.001). IBS patients had lower intake of vegetables (p = 0.026), dairy products (p = 0.004), and cereals (p = 0.010) compared with controls. Despite 21.5% of IBS patients were taking vitamin D supplements, 23.65% of them had vitamin D levels below 50 nmol/L, compared with 26.0% observed in the control group (p = 0.720). Vitamin D levels were lower in overweight than in normal weight IBS patients (60 (48-73) nmol/L vs. 65 (53-78) nmol/L, p = 0.022). Vitamin D correlated with cobalamin and folate but correlated inversely with TIBC and BMI. IBS patients had a high degree of gastrointestinal and extraintestinal symptoms, which were inversely associated with iron levels. Extraintestinal symptoms were associated with increased BMI.

IBS patients were often overweight or obese, with low vitamin D levels. High burden of extraintestinal symptoms were associated with overweight and lower iron levels.

ClinicalTrials.gov, NCT05192603 (Date of registration 11/29/2021) and NCT03306381 (Date of registration 09/18/2017), respectively.

The microbiota in our gut regulates the sophisticated metabolic system that the human body has, essentially converting food into energy and the building blocks for various bodily functions. In this review, we discuss the multifaceted impact of the microbiota on host nutritional status by producing short-chain fatty acids, influencing gut hormones and mediating bile acid metabolism, and the key role in maintaining intestinal barrier integrity and immune homeostasis. Understanding and leveraging the power of the gut microbiome holds tremendous potential for enhancing human health and preventing various diseases.

To prospectively explore the association of maternal serum 25(OH)D levels with the infant's gut microbiota in Chinese populations, and to evaluate its potential influence on the dynamic change patterns of offspring's gut microbiota from 1 to 6 months old.

Eighty-seven mother-infant dyads (vitamin D insufficient group vs. normal group = 59 vs. 28) were included in this longitudinal study. Two fecal samples were collected for the included infant at home by the parents at 1 month of age ("M1 phase") and 6 months of age ("M6 phase"). Gut microbiota were profiled by 16S rRNA gene sequencing. We performed mixed effects models on alpha diversity metrics, PERMANOVA tests on beta diversity distances, and linear discriminant analysis (LDA) to identify differently abundant taxa.

We observed significantly lower Pielou's evenness and Shannon diversity in the vitamin D insufficient group in the M6 phase (p = 0.049 and 0.015, respectively), but not in the M1 phase (p > 0.05), and the dynamic changes in alpha diversity from 1 to 6 months old were significantly different according to maternal vitamin D status (p < 0.05). There were also significant differences in gut microbiota composition between the vitamin D insufficient group and normal group, both in the M1 and M6 phases (LDA score > 2.0, p < 0.05). Moreover, among the predicted metagenome functions, pathways related to amino acid biosynthesis, starch degradation, and purine nucleotides biosynthesis were enriched in the vitamin D insufficient group.

Our findings highlight that maternal vitamin D status plays a pivotal role in shaping the early-life gut microbiota of the next generation.

Vitamin D, a crucial fat-soluble vitamin, is primarily synthesized in the skin upon exposure to ultraviolet radiation and is widely recognized as a bone-associated hormone. However, recent scientific advancements have unveiled its intricate association with gut health. The intestinal barrier serves as a vital component, safeguarding the intestinal milieu and maintaining overall homeostasis. Deficiencies in vitamin D have been implicated in altering the gut microbiome composition, compromising the integrity of the intestinal mucosal barrier, and predisposing individuals to various intestinal pathologies. Vitamin D exerts its regulatory function by binding to vitamin D receptors (VDR) present in immune cells, thereby modulating the production of pro-inflammatory cytokines and influencing the intestinal barrier function. Notably, numerous studies have reported lower serum vitamin D levels among patients suffering from intestinal diseases, including inflammatory bowel disease, irritable bowel syndrome, and celiac disease, highlighting the growing significance of vitamin D in gut health maintenance. This comprehensive review delves into the latest advancements in understanding the mechanistic role of vitamin D in modulating the gut microbiome and intestinal barrier function, emphasizing its pivotal role in immune regulation. Furthermore, we consolidate and present relevant findings pertaining to the therapeutic potential of vitamin D in the management of intestinal diseases.

The activation of the vitamin D receptor (VDR) in the ileum has been shown to regulate Paneth cell-specific defensins, a large family of antimicrobial peptides; hence, this may serve as a potential mechanism to maintain intestinal homeostasis. Previously, we have demonstrated that a combination of vitamin D3 (VD) and fructooligosaccharides (FOSs) upregulates colonic Vdr in mice. Here, we aim to examine the effect of VD, alone or in combination with FOSs, on intestinal barrier integrity and the secretion of antimicrobial peptides, as well as the gut microbial community. Male and female C57BL/6J mice at 6 weeks old were randomized into three groups to receive the following dietary regimens (n = 10/sex/group) for 8 weeks: (1) standard AIN-93G control diet (CTR), (2) CTR + 5000 IU vitamin D3 (VD), and (3) VD + 5% fructooligosaccharides (VF). VD and VF differentially regulated the mRNA expressions of tight junction proteins in the colon and ileum. VF suppressed the upregulation of colonic ZO-1 and occludin, which was induced by VD supplementation alone. In the ileum, occludin but not ZO-1 was upregulated 20-fold in the VF-treated mice. While VD did not alter the mRNA expressions of Vdr and defensins in the ileum, these targets were downregulated by VF. Microbial analysis further reveals a shift of microbial beta diversity and a reduction in Romboutsia ilealis, a pathobiont, in VF-treated mice. Though the implications of these phenotypical and microbial changes remain to be determined, the administration of FOSs in the presence of VD may serve as an effective dietary intervention for maintaining intestinal homeostasis.

Vitamin D deficiency has been linked to various chronic pain conditions. However, randomized trials of vitamin D supplementation have had mixed results. In contrast, systematic reviews of randomized trials indicate a protective effect of vitamin D supplementation on depression. We undertake a Mendelian randomization investigation in UK Biobank, a study of UK residents aged 40-65 at recruitment. We perform linear and non-linear Mendelian randomization analyses for four outcomes: fibromyalgia, clinical fatigue, chronic widespread pain, and probable lifetime major depression. We use genetic variants from four gene regions with known links to vitamin D biology as instruments. In linear analyses, genetically-predicted levels of 25-hydroxyvitamin D [25(OH)D], a clinical marker of vitamin D status, were not associated with fibromyalgia (odds ratio [OR] per 10 nmol/L higher 25(OH)D 1.02, 95% confidence interval [CI] 0.93, 1.12), clinical fatigue (OR 0.99, 95% CI 0.94, 1.05), chronic widespread pain (OR 0.95, 95% CI 0.89, 1.02), or probable lifetime major depression (OR 0.97, 95% CI 0.93, 1.01). In non-linear analyses, an association was observed between genetically-predicted 25(OH)D levels and depression in the quintile of the population with the lowest 25(OH)D levels (OR 0.75, 95% CI 0.59, 0.94); associations were null in other strata. Our findings suggest that population-wide vitamin D supplementation will not substantially reduce pain or depression; however, targeted supplementation of deficient individuals may reduce risk of depression.

The role of lipopolysaccharide (LPS) in the development of diseases is clear, but the specific mechanisms remain poorly understood. This study aimed to investigate the microbiome aberrations in the guts of mice against the background of LPS, as well as the anti-inflammatory effect of probiotic supplementation with Lactobacillus plantarum from the gut, a mix of commercial probiotic lactic acid bacteria, and Weissella confusa isolated from milk using next-generation sequencing. LPS injections were found to induce inflammatory changes in the intestinal mucosa. These morphological changes were accompanied by a shift in the microbiota. We found no significant changes in the microbiome with probiotic supplementation compared to the LPS group. However, when Lactobacillus plantarum and a mix of commercial probiotic lactic acid bacteria were used, the intestinal mucosa was restored. Weissella confusa did not contribute to the morphological changes of the intestinal wall or the microbiome. Changes in the microbiome were observed with probiotic supplementation of Lactobacillus plantarum and a mix of commercial probiotic lactic acid bacteria compared to the control group. In addition, when Lactobacillus plantarum was used, we observed a decrease in the enrichment of the homocysteine and cysteine interconversion pathways with an increase in the L-histidine degradation pathway.

Calcitriol has the potential to counteract fibrotic diseases beyond its classical action of maintaining calcium and bone metabolism; however, its functional mechanism remains unknown. Autophagy-related gene 16-like 1 (Atg16l1) is one of the genes related to autophagy and is involved in protecting against fibrotic diseases. The present study aimed to explore the contribution of autophagy to the inhibition of calcitriol-induced hepatic fibrosis, as well as its potential molecular mechanism.

Carbon tetrachloride (Ccl4)-treated mice were established as hepatic fibrosis models and received calcitriol treatment for 6 weeks. Quantification of Sirius red staining and measurement of key fibrotic markers (collagen-1 and α-SMA) was performed to detect hepatic fibrosis. Chloroquine (CQ) treatment was used to observe autophagic flux, and 3-methyladenine (3-MA) was used to inhibit autophagy. Furthermore, the effects of calcitriol on transforming growth factor β1 (TGFβ1)-stimulated primary hepatic stellate cells (HSCs) were detected. Downregulation of Atg16l1 or vitamin D receptor (VDR) in LX-2 cells was used to explore the mechanism of action of calcitriol in fibrosis and autophagy. Additionally, the electrophoretic mobility shift assay (EMSA) was used to investigate the interactions between VDR and ATG16L1.

Calcitriol increased the expression of VDR and ATG16L1, enhanced autophagy and attenuated hepatic fibrosis. 3-MA treatment and VDR silencing abolished the protective effects of calcitriol against fibrosis. Calcitriol-induced anti-fibrosis effects were blocked by ATG16L1 suppression. Furthermore, VDR bound to the ATG16L1 promoter and downregulation of VDR decreased the expression of ATG16L1 in LX-2 cells.

Calcitriol mitigates hepatic fibrosis partly through ATG16L1-mediated autophagy.

Vitamin D3 (VD3) is an essential nutrient for fish and participates in a variety of physiological activities. Notably, both insufficient and excessive supplementation of VD3 severely impede fish growth, and the requirements of VD3 for fish vary considerably in different species and growth periods. The present study aimed to evaluate the appropriate requirements of VD3 for juvenile grass carp (Ctenopharyngodon idella) according to growth performance and disease prevention capacity. In this study, diets containing six supplemental levels of VD3 (0, 300, 600, 1200, 2400, and 4800 IU/kg diet) were formulated to investigate the effect(s) of VD3 on the growth performance, antioxidant enzyme activities, and antimicrobial ability in juvenile grass carp. Compared with the VD3 deficiency group (0 IU/kg), the supplementation of 300-2400 IU/kg VD3 significantly enhanced growth performance and increased antioxidant enzyme activities in the fish liver. Moreover, dietary supplementation of VD3 significantly improved the intestinal health by manipulating the composition of intestinal microbiota in juvenile grass carp. In agreement with this notion, the mortality of juvenile grass carp fed with dietary VD3 was much lower than that in VD3 deficient group upon infection with Aeromonas hydrophila. Meanwhile, dietary supplementation of 300-2400 IU/kg VD3 reduced bacterial load in the spleen and head kidney of the infected fish, and 1200 IU/kg VD3 supplementation could decrease enteritis morbidity and increase lysozyme activities in the intestine. These findings strengthened the essential role of dietary VD3 in managing fish growth and antimicrobial capacity. Additionally, based on weight gain ratio and lysozyme activities, the appropriate VD3 requirements for juvenile grass carp were estimated to be 1994.80 and 2321.80 IU/kg diet, respectively.

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.

Vitamin D deficiency (VDD) during early life emerges as a potential risk factor for autism spectrum disorder (ASD). Individuals with autism commonly exhibit lower vitamin D (VD) levels compared to the general population, and VD deficiency is prevalent during pregnancy and lactation. Moreover, gastrointestinal comorbidity, prevalent in ASD patients, correlates closely with disruptions in the gut microbiota and altered intestinal permeability. Therefore, it is fascinating and significant to explore the effects of maternal VD deficiency during pregnancy and lactation on the maturation of the gut microbiota of the offspring and its relevance to autism spectrum disorders. In this study, we established maternal pregnancy and lactation VD-deficient mouse models, employed shotgun macrogenomic sequencing to unveil alterations in the gut microbiome of offspring mice, and observed autism-related behaviours. Furthermore, fecal microbial transplantation (FMT) reversed repetitive and anxious behaviours and alleviated social deficits in offspring mice by modulating the gut microbiota and increasing short-chain fatty acid levels in the cecum, along with influencing the concentrations of claudin-1 and occludin in the colon. Our findings confirm that VDD during pregnancy and lactation is a risk factor for autism in the offspring, with disturbances in the structure and function of the offspring's gut microbiota contributing at least part of the effect. The study emphasises the importance of nutrition and gut health early in life. Simultaneously, this study further demonstrates the effect of VDD on ASD and provides potential ideas for early prevention and intervention of ASD.

Vitamin D3 regulates a variety of biological processes irrespective of its well-known importance for calcium metabolism. Epidemiological and animal studies indicate a role in immune regulation, intestinal barrier function and microbiome diversity. Here, we analyzed the impact of different vitamin D3- containing diets on C57BL/6 and BALB/c mice, with a particular focus on gut homeostasis and also investigated effects on immune cells in vitro. Weak regulatory effects were detected on murine T cells. By trend, the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 suppressed IFN, GM-CSF and IL-10 cytokine secretion in T cells of C57BL/6 but not BALB/c mice, respectively. Using different vitamin D3-fortified diets, we found a tissue-specific enrichment of mainly CD11b+ myeloid cells but not T cells in both mouse strains e.g. in spleen and Peyer's Patches. Mucin Reg3γ and Batf expression, as well as important proteins for gut homeostasis, were significantly suppressed in the small intestine of C57BL76 but not BALB/c mice fed with a high-vitamin D3 containing diet. Differences between both mouse stains were not completely explained by differences in vitamin D3 receptor expression which was strongly expressed in epithelial cells of both strains. Finally, we analyzed gut microbiome and again an impact of vitamin D3 was detected in C57BL76 but not BALB/c. Our data suggest strain-specific differences in vitamin D3 responsiveness under steady state conditions which may have important implications when choosing a murine disease model to study vitamin D3 effects.

The link between gut and lung starts as early as during organogenesis. Even though they are anatomically distinct, essential bidirectional crosstalk via complex mechanisms supports GLA. Emerging studies have demonstrated the association of gut and lung diseases via multifaceted mechanisms. Advancements in omics and metagenomics technologies revealed a potential link between gut and lung microbiota, adding further complexity to GLA. Despite substantial studies on GLA in various disease models, mechanisms beyond microbial dysbiosis regulating the interplay between gut and lung tissues during disease conditions are not thoroughly reviewed. This review outlines disease specific GLA mechanisms, emphasizing research gaps with a focus on gut-to-lung direction based on current GLA literature. Moreover, the review discusses potential gut microbiota and their products like metabolites, immune modulators, and non-bacterial contributions as a basis for developing treatment strategies for lung diseases. Advanced experimental methods, modern diagnostic tools, and technological advancements are also highlighted as crucial areas for improvement in developing novel therapeutic approaches for GLA-related diseases. In conclusion, this review underscores the importance of exploring additional mechanisms within the GLA to gain a deeper understanding that could aid in preventing and treating a wide spectrum of lung diseases.

A vitamin D receptor (VDR) deficiency leads to the dysbiosis of intestinal bacteria and is associated with various diseases, including cancer, infections, and inflammatory bowel disease. However, the impact of a VDR deficiency on fungi and archaea is unknown. We conditionally deleted the VDR in Paneth cells (VDRΔPC), intestinal epithelial cells (VDRΔIEC), or myeloid cells (VDRΔLyz) in mice and collected feces for shotgun metagenomic sequencing and untargeted metabolomics. We found that fungi were significantly altered in each knockout (KO) group compared to the VDRLoxp control. The VDRΔLyz mice had the most altered fungi species (three depleted and seven enriched), followed by the VDRΔPC mice (six depleted and two enriched), and the VDRΔIEC mice (one depleted and one enriched). The methanogen Methanofollis liminatans was enriched in the VDRΔPC and VDRΔLyz mice and two further archaeal species (Thermococcus piezophilus and Sulfolobus acidocaldarius) were enriched in the VDRΔLyz mice compared to the Loxp group. Significant correlations existed among altered fungi, archaea, bacteria, and viruses in the KO mice. Functional metagenomics showed changes in several biologic functions, including decreased sulfate reduction and increased biosynthesis of cobalamin (vitamin B12) in VDRΔLyz mice relative to VDRLoxp mice. Fecal metabolites were analyzed to examine the involvement of sulfate reduction and other pathways. In conclusion, a VDR deficiency caused the formation of altered fungi and archaea in a tissue- and sex-dependent manner. These results provide a foundation about the impact of a host factor (e.g., VDR deficiency) on fungi and archaea. It opens the door for further studies to determine how mycobiome and cross-kingdom interactions in the microbiome community and metabolites contribute to the risk of certain diseases.

The interplay between the human microbiome and the musculoskeletal system represents a burgeoning field of research with profound implications for understanding and treating musculoskeletal disorders. This review articulates the pivotal role of the microbiome in modulating bone health, highlighting the gut-bone axis as a critical nexus for potential therapeutic intervention. Through a meticulous analysis of recent clinical research, we underscore the microbiome's influence on osteoporosis, sarcopenia, osteoarthritis, and rheumatoid arthritis, delineating both the direct and indirect mechanisms by which microbiota could impact musculoskeletal integrity and function. Our investigation reveals novel insights into the microbiota's contribution to bone density regulation, hormone production, immune modulation, and nutrient absorption, laying the groundwork for innovative microbiome-based strategies in musculoskeletal disease management. Significantly, we identify the challenges hindering the translation of research into clinical practice, including the limitations of current microbial sequencing techniques and the need for standardized methodologies in microbiome studies. Furthermore, we highlight promising directions for future research, particularly in the realm of personalized medicine, where the microbiome's variability offers unique opportunities for tailored treatment approaches. This review sets a new agenda for leveraging gut microbiota in the diagnosis, prevention, and treatment of musculoskeletal conditions, marking a pivotal step toward integrating microbiome science into clinical musculoskeletal care.

The gut microbiome has been linked to many diseases with sex bias including autoimmune, metabolic, neurological, and reproductive disorders. While numerous studies report sex differences in fecal microbial communities, the role of the reproductive axis in this differentiation is unclear and it is unknown how sex differentiation affects microbial diversity in specific regions of the small and large intestine.

We used a genetic hypogonadal mouse model that does not produce sex steroids or go through puberty to investigate how sex and the reproductive axis impact bacterial diversity within the intestine. Using 16S rRNA gene sequencing, we analyzed alpha and beta diversity and taxonomic composition of fecal and intestinal communities from the lumen and mucosa of the duodenum, ileum, and cecum from adult female (n = 20) and male (n = 20) wild-type mice and female (n = 17) and male (n = 20) hypogonadal mice.

Both sex and reproductive axis inactivation altered bacterial composition in an intestinal section and niche-specific manner. Hypogonadism was significantly associated with bacteria from the Bacteroidaceae, Eggerthellaceae, Muribaculaceae, and Rikenellaceae families, which have genes for bile acid metabolism and mucin degradation. Microbial balances between males and females and between hypogonadal and wild-type mice were also intestinal section-specific. In addition, we identified 3 bacterial genera (Escherichia Shigella, Lachnoclostridium, and Eggerthellaceae genus) with higher abundance in wild-type female mice throughout the intestinal tract compared to both wild-type male and hypogonadal female mice, indicating that activation of the reproductive axis leads to female-specific differentiation of the gut microbiome. Our results also implicated factors independent of the reproductive axis (i.e., sex chromosomes) in shaping sex differences in intestinal communities. Additionally, our detailed profile of intestinal communities showed that fecal samples do not reflect bacterial diversity in the small intestine.

Our results indicate that sex differences in the gut microbiome are intestinal niche-specific and that sampling feces or the large intestine may miss significant sex effects in the small intestine. These results strongly support the need to consider both sex and reproductive status when studying the gut microbiome and while developing microbial-based therapies.

Although no causative microbe has been yet identified or successfully targeted in the treatment of inflammatory bowel disease (IBD), the role of Escherichia coli in the pathogenesis of Crohn's disease has attracted considerable interest.

In this review, we present a literature overview of the interactions between diet and E. coli and other Proteobacteria in the aetiology, outcomes and management of IBD and suggest future research directions.

An extensive literature search was performed to identify in vitro studies and research in animal models that explored mechanisms by which dietary components can interact with E. coli or Proteobacteria to initiate or propagate gut inflammation. We also explored the effect diet and dietary therapies have on the levels of E. coli or Proteobacteria in patients with IBD.

Preclinical data suggest that the Western diet and its components influence the abundance, colonisation and phenotypic behaviour of E. coli in the gut, which may in turn initiate or contribute to gut inflammation. In contrast, the Mediterranean diet and specific dietary fibres may abrogate these effects and protect from inflammation. There are limited data from clinical trials, mostly from patients with Crohn's disease during treatment with exclusive enteral nutrition, with findings often challenging observations from preclinical research. Data from patients with ulcerative colitis are sparse.

Preclinical and some clinical trial data suggest that E. coli and other Proteobacteria interact with certain dietary components to promote gut inflammation. Well-designed clinical trials are required before dietary recommendations for disease management can be made.

Vitamin D (VD) is a secosteroid hormone that is renowned for its crucial role in phospho-calcium homeostasis upon binding to the nuclear vitamin D receptor (VDR). Over and above, the pleiotropic immunomodulatory, anti-inflammatory, and metabolic roles VD plays in different disease settings started to surface in the past few decades. On the other hand, a growing body of evidence suggests a correlation between non-alcoholic fatty liver disease (NAFLD) and its progressive inflammatory form non-alcoholic steatohepatitis (NASH) with vitamin D deficiency (VDD) owing to the former's ingrained link with obesity and metabolic syndrome. Accordingly, a better understanding of the contribution of disrupted VDR signalling to NAFLD incidence and progression would provide further insights into its diagnosis, treatment modalities, and prognosis. This is especially significant as, hitherto, no drug for NAFLD has been approved. This review, therefore, sought to set forth the likely contribution of VDR signalling in NAFLD and how it might influence its multiple drivers.

An infant's gut microbiome plays a vital role in their health, and various factors can impact their gut microbiota composition. This review aimed to summarize the current knowledge regarding the associations between maternal prenatal supplementation with vitamin D and the composition of infants' gut microbiota.

A comprehensive systematic search was done on Web of Science, Scopus, PubMed, ScienceDirect, and Google Scholar databases without date restrictions until December 2022 using relevant keywords. All relevant original articles in English were eligible for the present review.

Eight articles (two mice, three randomized clinical trials, and three cohort studies) were included in this review. The included mice studies reported that maternal prenatal vitamin D supplementation significantly affects the offspring's gut microbiome composition (such as enhancing the abundance of colonic Bacteroides). Moreover, the included cohort studies revealed a significant association between maternal supplementation with vitamin D during pregnancy and the infant's gut microbiome. However, one-third of clinical trials indicated that vitamin D levels in utero could influence the colonization of the microbial community in the infant's gut.

The findings of this review revealed that maternal vitamin D supplementation during pregnancy was linked to an infant's gut microbiome and could impact their gut microbiota composition. However, more studies are warranted to confirm these results.

Apart from developmental disabilities, the prevalence of chronic diseases increases with age especially in those with co-morbidities: vitamin D deficiency plays a major role in it. Whether vitamin D deficiency initiates and/or aggravates chronic diseases or vice versa is unclear. It adversely affects all body systems but can be eliminated using proper doses of vitamin D supplementation and/or safe daily sun exposure. Maintaining the population serum 25(OH)D concentration above 40 ng/mL (i.e., sufficiency) ensures a sound immune system, minimizing symptomatic diseases and reducing infections and the prevalence of chronic diseases. This is the most cost-effective way to keep a population healthy and reduce healthcare costs. Vitamin D facilitates physiological functions, overcoming pathologies such as chronic inflammation and oxidative stress and maintaining broader immune functions. These are vital to overcoming chronic diseases and infections. Therefore, in addition to following essential public health and nutritional guidance, maintaining vitamin D sufficiency should be an integral part of better health, preventing acute and chronic diseases and minimize their complications. Those with severe vitamin D deficiency have the highest burdens of co-morbidities and are more vulnerable to developing complications and untimely deaths. Vitamin D adequacy improves innate and adaptive immune systems. It controls excessive inflammation and oxidative stress, generates antimicrobial peptides, and neutralizes antibodies via immune cells. Consequently, vitamin D sufficiency reduces infections and associated complications and deaths. Maintaining vitamin D sufficiency reduces chronic disease burden, illnesses, hospitalizations, and all-cause mortality. Vulnerable communities, such as ethnic minorities living in temperate countries, older people, those with co-morbidities, routine night workers, and institutionalized persons, have the highest prevalence of vitamin D deficiency-they would significantly benefit from vitamin D and targeted micronutrient supplementation. At least now, health departments, authorities, and health insurance companies should start assessing, prioritizing, and encouraging this economical, non-prescription, safe micronutrient to prevent and treat acute and chronic diseases. This approach will significantly reduce morbidity, mortality, and healthcare costs and ensure healthy aging.

Colorectal cancer (CRC) remains the third most common form of cancer and, despite its reduced mortality, results in over 50,000 deaths annually, highlighting the need for novel therapeutic approaches. VAX014 is a novel clinical-stage, oncolytic bacterial minicell-based therapy shown to elicit protective antitumor immune responses in cancer, but it has not been fully evaluated in CRC. Here, VAX014 was demonstrated to induce oncolysis in CRC cell lines in vitro and was evaluated in vivo, both as a prophylactic (before spontaneous development of adenomatous polyps) and as a neoadjuvant treatment using the Fabp-CreXApc^fl468 preclinical animal model of colon cancer. As a prophylactic, VAX014 significantly reduced the size and number of adenomas without inducing long term changes in the gene expression of inflammatory, T helper 1 antitumor, and immunosuppression markers. In the presence of adenomas, a neoadjuvant VAX014 treatment reduced the number of tumors, induced the gene expression of antitumor T_H1 immune markers in adenomas, and promoted the expansion of the probiotic bacterium Akkermansia muciniphila. The neoadjuvant VAX014 treatment was associated with decreased Ki67 proliferation in vivo, suggesting that VAX014 inhibits adenoma development through both oncolytic and immunotherapeutic effects. Combined, these data support the potential of VAX014 treatment in CRC and "at risk" polyp-bearing or early adenocarcinoma populations.

Cross talk between immune cells and the intestinal crypt is critical in maintaining intestinal homeostasis. Recent studies highlight the direct impact of vitamin D receptor (VDR) signaling on intestinal and microbial homeostasis. However, the tissue-specific role of immune VDR signaling is not fully understood. Here, we generated a myeloid-specific VDR knockout (VDRΔLyz ) mouse model and used a macrophage/enteroids coculture system to examine tissue-specific VDR signaling in intestinal homeostasis. VDRΔLyz mice exhibited small intestine elongation and impaired Paneth cell in maturation and localization. Coculture of enteroids with VDR-/- macrophages increased the delocalization of Paneth cells. VDRΔLyz mice exhibited significant changes in the microbiota taxonomic and functional files, and susceptibility to Salmonella infection. Interestingly, loss of myeloid VDR impaired Wnt secretion in macrophages, thus inhibiting crypt β-catenin signaling and disrupting Paneth cell differentiation in the epithelium. Taken together, our data have demonstrated that myeloid cells regulate crypt differentiation and the microbiota in a VDR-dependent mechanism. Dysregulation of myeloid VDR led to high risks of colitis-associated diseases. Our study provided insight into the mechanism of immune/Paneth cell cross talk in regulating intestinal homeostasis.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with increasing prevalence worldwide. The genetic and molecular background of NAFLD pathogenesis is not yet clear. The vitamin D/vitamin D receptor (VDR) axis is significantly associated with the development and progression of NAFLD. Gene polymorphisms may influence the regulation of the VDR gene, although their biological significance remains to be elucidated. VDR gene polymorphisms are associated with the presence and severity of NAFLD, as they may influence the regulation of adipose tissue activity, fibrosis, and hepatocellular carcinoma (HCC) development. Vitamin D binds to the hepatic VDR to exert its biological functions, either by activating VDR transcriptional activity to regulate gene expression associated with inflammation and fibrosis or by inducing intracellular signal transduction through VDR-mediated activation of Ca²⁺ channels. VDR activity has protective and detrimental effects on hepatic steatosis, a characteristic feature of NAFLD. Vitamin D-VDR signaling may control the progression of NAFLD by regulating immune responses, lipotoxicity, and fibrogenesis. Elucidation of the genetic and molecular background of VDR in the pathophysiology of NAFLD will provide new therapeutic targets for this disease through the development of VDR agonists, which already showed promising results in vivo.

Obesity has been a worldwide problem associated with numerous chronic diseases such as cardiovascular disease, type 2 diabetes, and metabolic disorders. It may also play a role in visceral hypersensitivity, contributing to irritable bowel syndrome. (i) Adipose tissue secretes various inflammatory mediators, causing intestinal hyperpermeability and nerve endings activation. (ii) Obesity and gastrointestinal microbiota could affect each other, and microbial metabolites can increase sensitivity of the colon. (iii) Vitamin D deficiency contributes to both fat accumulation and disruption of the intestinal mucosal barrier. (iv) Brain-gut axis may be another bridge from obesity to visceral hypersensitivity.

Metabolic syndrome (MetSyn) is a precursor for several cardiometabolic diseases such as obesity, type-2 diabetes mellitus (T2DM), and cardiovascular diseases. Emerging evidence suggests that vitamin D deficiency links to cardiometabolic diseases through microbiota. A combination of poor vitamin D status and dysbiosis may contribute to the progression of cardiometabolic diseases. Therefore, in this review, we present the relationship among vitamin D, microbiota, and cardiometabolic diseases with a focus on MetSyn. We searched major databases for reports on vitamin D, microbiota, and MetSyn until June 2022. We reviewed 13 reports on the relation between vitamin D and MetSyn (6 randomized controlled and 7 cross-sectional studies) and 6 reports on the effect of vitamin D on the gut microbiome. Adequate vitamin D status has a beneficial effect on gut microbiota, therefore preventing the progression of MetSyn. Further, well-controlled studies are needed for a better understanding of the mechanisms of action involving vitamin D and microbiota in the pathogenesis of cardiometabolic diseases.

Vitamin D and its receptor (VDR) effects on the gastrointestinal system are among its most critical multisystemic effects.

This study aimed to reveal that VDR gene polymorphisms may constitute a risk factor for necrotizing enterocolitis (NEC). VDR Fok1-Bsm1-Apa single-nucleotide polymorphisms were analyzed in the NEC group (n = 74) and the control group (n = 147). Among 1112 babies at and below 36 weeks of gestational age who were hospitalized between January 2013 and December 2016 with a diagnosis of prematurity, 74 of a total of 148 patients who developed NEC during follow-up (NEC group) were included in the study. When NEC was diagnosed according to clinical and radiological findings and staged using Modified Bell criteria, 9 (12.1%) of 74 babies were stage 1A, 13 (17.5%) stage 1B, and 5 (6.7%) stage 2A, 33 (44.5%) stage 2B, 7 (9.4%) stage 3A, 7 (9.4%) stage 3B. Of 964 babies who did not develop NEC during follow-up, 147 were included as the control group in the study. Genotyping of VDR polymorphisms was assayed by real-time PCR. From 221 premature babies in the NEC and control groups, 2 ml peripheral blood was taken appropriately and meticulously into an EDTA tube. DNA was isolated from these blood samples. DNA amplification was performed using a thermal cycler (Applied Biosystems GeneAmp PCR System 9600).

When the two groups were compared in terms of the prevalence of VDR Fok1 C/T genotype, it was found that TT genotype increased the risk of NEC by 2.697 times, and there was a significant relationship between TT genotype and the risk of NEC (p = 0.041). Multivariable logistic regression analysis was performed in terms of gestational age, birth weight, VDR gene polymorphism data between NEC and the control group. According to the analysis results, TT polymorphism, increased the risk of disease 4.5 times (p = 0.033).

Fok 1 C > T polymorphism in the VDR gene plays a role in the development of NEC. Identifying the risk groups by detecting gene polymorphisms that cause increased susceptibility to NEC may assist in the follow-up of these patients and in making early treatment decisions for them.

In this study examining the non-bone effects of the genetic differences in vitamin D metabolism in premature babies, Fok 1 polymorphism has been observed to be an essential risk factor for NEC. This is the first study in our country that has investigated the relationship between VDR gene polymorphism and necrotizing enterocolitis among the Turkish population. Identifying the risk groups by detecting gene polymorphisms that cause increased susceptibility to NEC may assist in the monitoring of these patients and in making early treatment decisions for them.

Vitamin D (VD) plays a vital role in various physiological processes in addition to its classic functions on maintaining the balance of Ca and P metabolism. However, there still are gaps to understand in depth the issues on the precise requirement, metabolic processes and physiological functions of VD in fish. In this study, we investigated the effects of VD on the growth, intestinal health, host immunity and metabolism in turbot (Scophthalmus maximus L.), one important commercial carnivorous fish in aquaculture, through the supplementation of different doses of dietary VD3 (0, 200, 400, 800 and 1600 μg VD3/kg diet). According to our results, the optimal VD3 level in the feed for turbot growth was estimated to be around 400 IU/kg, whereas VD3 deficiency or overdose in diets induced the intestinal inflammation, lowered the diversity of gut microbiota and impaired the host resistance to bacterial infection in turbot. Moreover, the level of 1α,25(OH)2D3, the active metabolite of VD3, reached a peak value in the turbot serum in the 400 μg group, although the concentrations of Ca and phosphate in the turbot were stable in all groups. Finally, the deficiency of dietary VD3 disturbed the nutritional metabolism in turbot, especially the metabolism of lipids and glucose. In conclusion, this study evaluated the optimal dose of dietary VD3 for turbot and provided the evidence that VD has a significant impact on intestinal health, host immunity and nutritional metabolism in fish, which deepened our understanding on the physiological functions and metabolism of VD3 in fish.

A Western-style diet that is high in fat and sucrose has been shown to alter DNA methylation and epigenetically modify genes related to health risk in offspring. Here, we investigated the effect of a methyl-donor nutrient (MS) supplemented to a high-fat, high-sucrose (HFS) diet during pregnancy and lactation on vitamin D (VD) status and inflammatory response in offspring. After mating, 10-week-old female Sprague-Dawley (SD) rats (n = 10/group) were randomly assigned to one of the four dietary groups during pregnancy and lactation: (1) control diet (CON), (2) CON with MS (CON-MS), (3) HFS, and (4) HFS with MS (HFS-MS). Weanling offspring (three weeks old) were euthanized and sacrificed (n = 8-10/sex/group). The remaining offspring (n = 10/sex/group) were randomly assigned to either a CON or an HFS diet for 12 weeks and sacrificed at 15 weeks of age. Our results indicated that prenatal MS supplementation, but not postnatal diet, restored low vitamin D status and suppressed elevation of proinflammatory cytokine induced by maternal HFS in the offspring. Furthermore, both prenatal and postnatal diets modulated the abundance of Lactobacillus spp. and Bacteroides spp. in the offspring, a shift that was independent of vitamin D status. Collectively, our data support a role for MS in restoring the perturbation of VD status and normalizing maternal HFS-induced inflammation in the offspring. Further investigation is warranted to elucidate the methylation status of VD metabolism-related pathways in the offspring, as well as the immunomodulatory role of vitamin D during the progression of obesity.

Obesity is the result of the long-term energy imbalance between the excess calories consumed and the few calories expended. Reducing the intake of energy dense foods (fats, sugars), and strategies such as fasting and caloric restriction can promote body weight loss. Not only energy in terms of calories, but also the specific composition of the diet can affect the way the food is absorbed and how its energy is stored, used or dissipated. Recent research has shown that bioactive components of food, such as polyphenols and vitamins, can influence obesity and its pathologic complications such as insulin resistance, inflammation and metabolic syndrome. Individual micronutrients can influence lipid turnover but for long-term effects on weight stability, dietary patterns containing several micronutrients may be required. At the molecular level, these molecules modulate signaling and the expression of genes that are involved in the regulation of energy intake, lipid metabolism, adipogenesis into white, beige and brown adipose tissue, thermogenesis, lipotoxicity, adipo/cytokine synthesis, and inflammation. Higher concentrations of these molecules can be reached in the intestine, where they can modulate the composition and action of the microbiome. In this review, the molecular mechanisms by which bioactive compounds and vitamins modulate energy metabolism, inflammation and obesity are discussed.

Several studies suggest a role of gut microbiota in colorectal cancer (CRC) initiation and progression. Vitamin D (vitD) blood levels are also inversely correlated with CRC risk and prognosis. However, these factors' interplay remains unknown.

74 CRC patients after standard treatment were randomized to 1-year 2000 IU/day vitD or placebo.  Baseline and post-treatment fecal microbiota for shotgun metagenomics sequencing was collected. Coda-lasso and Principal Component Analysis were used to select and summarize treatment-associated taxa and pathways. Associations between vitD and taxa/pathways were investigated with logistic regression. Mediation analysis was performed to study if treatment-associated taxa mediated the effect of supplementation on 25(OH)D levels. Cox proportional-hazards model was used for disease-free survival (DFS).

60 patients were analyzed. Change in alpha diversity (Shannon: p = 0.77; Simpson: p = 0.63) and post-treatment beta diversity (p = 0.70) were comparable between arms. Post-treatment abundances of 63 taxa and 32 pathways differed between arms. The 63 taxa also mediated the effect of supplementation on 25(OH)D (p = 0.02). There were sex differences in vitD levels, microbiota and pathways. Pathways of essential amino acids' biosynthesis were more abundant in supplemented women. Fusobacterium nucleatum presence at baseline was associated with worse DFS (p = 0.02). Those achieving vitD sufficiency (25(OH)D≥30 ng/ml) had lower post-treatment abundances (p = 0.05). Women were more likely to have F. nucleatum post-treatment (p = 0.02).

VitD supplementation may contribute shaping the gut microbiota and the microbiota may partially mediate the effect of supplementation on 25(OH)D. The observed sex-specific differences highlight the necessity of including sex/gender as a variable in microbiome studies.

Bile acids play a significant role in the digestion of nutrients. In addition, bile acids perform a signaling function through their blood-circulating fraction. They regulate the activity of nuclear and membrane receptors, located in many tissues. The gut microbiota is an important factor influencing the effects of bile acids via enzymatic modification. Depending on the rate of healthy and pathogenic microbiota, a number of bile acids may support lipid and glucose homeostasis as well as shift to more toxic compounds participating in many pathological conditions. Thus, bile acids can be possible biomarkers of human pathology. However, the chemical structure of bile acids is similar and their analysis requires sensitive and specific methods of analysis. In this review, we provide information on the chemical structure and the biosynthesis of bile acids, their regulation, and their physiological role. In addition, the review describes the involvement of bile acids in various diseases of the digestive system, the approaches and challenges in the analysis of bile acids, and the prospects of their use in omics technologies.

Recent studies indicate that the interplay between diet, intestinal microbiota composition, and intestinal permeability can impact mental health. More than 10% of children and adolescents in Iceland suffer from mental disorders, and rates of psychotropics use are very high. The aim of this novel observational longitudinal case-control study, "Meals, Microbiota and Mental Health in Children and Adolescents (MMM-Study)" is to contribute to the promotion of treatment options for children and adolescents diagnosed with mental disorders through identification of patterns that may affect the symptoms. All children and adolescents, 5-15 years referred to the outpatient clinic of the Child and Adolescent Psychiatry Department at The National University Hospital in Reykjavik, Iceland, for one year (n≈150) will be invited to participate. There are two control groups, i.e., sex-matched children from the same postal area (n≈150) and same parent siblings (full siblings) in the same household close in age +/- 3 years (n<150). A three-day food diary, rating scales for mental health, and multiple questionnaires will be completed. Biosamples (fecal-, urine-, saliva-, blood samples, and buccal swab) will be collected and used for 16S rRNA gene amplicon sequencing of the oral and gut microbiome, measurements of serum factors, quantification of urine metabolites and host genotype, respectively. For longitudinal follow-up, data collection will be repeated after three years in the same groups. Integrative analysis of diet, gut microbiota, intestinal permeability, serum metabolites, and mental health will be conducted applying bioinformatics and systems biology approaches. Extensive population-based data of this quality has not been collected before, with collection repeated in three years' time, contributing to the high scientific value. The MMM-study follows the "Strengthening the Reporting of Observational Studies in Epidemiology" (STROBE) guidelines. Approval has been obtained from the Icelandic National Bioethics Committee, and the study is registered with Clinicaltrials.gov. The study will contribute to an improved understanding of the links between diet, gut microbiota and mental health in children through good quality study design by collecting information on multiple components, and a longitudinal approach. Furthermore, the study creates knowledge on possibilities for targeted and more personalized dietary and lifestyle interventions in subgroups. Trial registration numbers: VSN-19-225 & NCT04330703.