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Schematic of the physical and functional intestinal epithelial barrier. The physical barrier is composed of a thin and thick mucus layer, followed by single cell layer consisting of enterocytes, Paneth cells, goblet cells, and microfold (M) cells. The integrity of this layer is maintained via intact tight junctions. Functionally, the epithelium produces mucin and antimicrobial peptides, and allows translocation of secretory immunoglobulin A. Intestinal immune cells sample the luminal environment, respond to invasive pathogens, and coordinate innate and adaptive immune responses. SCFA, vitamin D, and polysaccharide A have all been shown to promote regulatory adaptive responses, whereas bacteria generally promote proinflammatory responses. SCFA, short chain fatty acids; PsA, polysaccharide A; sIgA, secretory IgA; Ag, antigen; M cell, microfold cell. Illustration by David Schumick, BS, CMI. Reprinted with the permission of the Cleveland Clinic Center for Medical Art & Photography © 2019. All rights reserved.
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There is increasing recognition of the role the microbiome plays in states of health and disease. Microbiome studies in systemic autoimmune diseases demonstrate unique microbial patterns in Inflammatory Bowel Disease, Rheumatoid Arthritis, and Systemic Lupus Erythematosus to a lesser extent, whereas there is no single bug or pattern that characteri...
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(1) Background: Vitamin D is an immunoregulatory factor influencing intestinal homeostasis. Recent evidence supports a central role of this micronutrient in the course of Inflammatory Bowel Diseases (IBD). This narrative review aims to provide a general overview of the possible biological mechanisms of action of vitamin D and its therapeutic implic...
Citations
... There is growing evidence on the importance of the vitamin D pathway for intestinal homeostasis and signaling between gut microbiota and the host [104]. At higher concentrations, vitamin D favors the growth of protective microbiota, whereas low levels lead to a permeable barrier, outgrowth of harmful bacteria and increased inflammation [105]. ...
There is increasing evidence that probiotic and commensal bacteria play a role in substrate metabolism, energy harvesting and intestinal homeostasis, and may exert immunomodulatory activities on human health. In addition, recent research suggests that these microorganisms interact with vitamins and minerals, promoting intestinal and metabolic well-being while producing vital microbial metabolites such as short-chain fatty acids (SCFAs). In this regard, there is a flourishing field exploring the intricate dynamics between vitamins, minerals, SCFAs, and commensal/probiotic interactions. In this review, we summarize some of the major hypotheses beyond the mechanisms by which commensals/probiotics impact gut health and their additional effects on the absorption and metabolism of vitamins, minerals, and SCFAs. Our analysis includes comprehensive review of existing evidence from preclinical and clinical studies, with particular focus on the potential interaction between commensals/probiotics and micronutrients. Finally, we highlight knowledge gaps and outline directions for future research in this evolving field.
... Concerning Systemic Lupus Erythematosus, there are conflicting results from a limited number of studies indicating a smaller Firmicutes-to-Bacteroidetes (F:B) ratio compared to healthy individuals. It appears that this ratio is not well-established as a clear cause or consequence, as it could be both simultaneously (143). Howbeit, Enterococcus gallinarum, member of gut commensals of the Firmicutes, appears to promote a lupus-like disease (140) In Inflammatory Bowel Disease (IBD), specifically in ulcerative colitis (UC) patients, Faecalibacterium prausnitzii is reduced in feces. ...
... In Crohn's disease biopsies, Faecalibacterium prausnitzii (F. prausnitzii) is also detected (143). ...
... They encompass products that are isolated or purified from foods. Established nutraceuticals include probiotics, prebiotics, omega-3 and -6 fatty acids, and others like polyphenols, phytoestrogens, flavonoids and antioxidants, with already recognized favorable effects under specific conditions (143)(144)(145)(146)(147)(148). Nutraceuticals are "related" to the human microbiota that includes 6 taxonomic bacterial phyla with Firmicutes and Bacteriodetes occupying the 90% of the host's colonized areas (149). ...
The nutritional habits regulate the gut microbiota and increase risk of an autoimmune disease. Western diet is rich in sugars, meat, and poly-unsaturated fatty acids, which lead to dysbiosis of intestinal microbiota, disruption of gut epithelial barrier and chronic mucosal inflammation. In contrast, the Mediterranean Diet (MedDiet) is abundant in ω3 fatty acids, fruits, and vegetables, possessing anti-inflammatory properties that contribute to the restoration of gut eubiosis. Numerous studies have extensively examined the impact of MedDiet and its components on both health and various disease states. Additionally, specific investigations have explored the correlation between MedDiet, microbiota, and the risk of autoimmune diseases. Furthermore, the MedDiet has been linked to a reduced risk of cardiovascular diseases, playing a pivotal role in lowering mortality rates among individuals with autoimmune diseases and comorbidities. The aim of the present review is to specifically highlight current knowledge regarding possible interactions of MedDiet with the patterns of intestinal microbiota focusing on autoimmunity and a blueprint through dietary modulations for the prevention and management of disease’s activity and progression.
... T he micronutrient vitamin D has an important role in immune modulation and in shaping commensal microbial communities (1)(2)(3)(4)(5)(6). Vitamin D has also been studied for its potential role in cancer, with reports showing that it can decrease cancer cell proliferation, promote apoptosis, reduce angiogenesis (7)(8)(9), and dampen the protumorigenic activity of cancer-associated fibroblasts (10,11). ...
A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D–induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival. In mice, resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of Bacteroides fragilis , which positively regulates cancer immunity. Our findings indicate a previously unappreciated connection between vitamin D, microbial commensal communities, and immune responses to cancer. Collectively, they highlight vitamin D levels as a potential determinant of cancer immunity and immunotherapy success.
... The relationship between the intestinal microbiome and multiple systemic pathologies such as atopy (asthma), autoimmunity (SLE, celiac disease) or even postinfectious irritable bowel syndrome is well known. In the case of SLE, the presence of autoimmunity is marked at the intestinal level mainly by a low Firmicutes -Bacteroidetes ratio, together with an increase in Prevotella, Rhodococcus, Eggerthella and Klebsiella (35)(36)(37)(38)(39). Vitamin D3 also exerts effects on the integrity of the intestinal barrier, the bacterial translocation capacity and the microbial balance, thus revealing another way through which it can mediate interactions with the host's immune system, imprinting the pathogenesis of SLE (35). ...
... The relationship between the intestinal microbiome and multiple systemic pathologies such as atopy (asthma), autoimmunity (SLE, celiac disease) or even postinfectious irritable bowel syndrome is well known. In the case of SLE, the presence of autoimmunity is marked at the intestinal level mainly by a low Firmicutes -Bacteroidetes ratio, together with an increase in Prevotella, Rhodococcus, Eggerthella and Klebsiella (35)(36)(37)(38)(39). Vitamin D3 also exerts effects on the integrity of the intestinal barrier, the bacterial translocation capacity and the microbial balance, thus revealing another way through which it can mediate interactions with the host's immune system, imprinting the pathogenesis of SLE (35). ...
Having increased popularity during the Covid-19 pandemic, vitamin D3 is currently impressing thanks to the numerous researches aimed at its interactions with the body’s homeostasis. At the same time, there is a peak in terms of recommendations for supplementation with it. Some of the studies focus on the link between autoimmune diseases and nutritional deficiencies, especially vitamin D3. Since the specialized literature aimed at children (patients between 0-18 years old) is far from equal to the informational diversity of the adult-centered branch, this review aims to bring up to date the relationship between the microbial and nutritional balance and the activity of pediatric systemic lupus erythematosus (pSLE). The desired practical purpose resides in a better understanding and an adequate, individualized management of the affected persons to reduce morbidity. The center of the summary is to establish the impact of hypovitaminosis D in the development and evolution of pediatric lupus erythematosus. We will address aspects related to the two entities of the impact played by vitamin D3 in the pathophysiological cascade of lupus, but also the risk of toxicity and its effects when the deficiency is over supplemented (hypervitaminosis D). We will debate the relationship of hypovitaminosis D with the modulation of immune function, the potentiation of inflammatory processes, the increase of oxidative stress, the perfusion of cognitive brain areas, the seasonal incidence of SLE and its severity. Finally, we review current knowledge, post-pandemic, regarding the hypovitaminosis D – pSLE relationship.
... Butyrate produced by Ruminococcaceae family bacteria can promote the synthesis of vitamin D in the body (Murdaca et al., 2021). Studies have found that vitamin D has a regulatory effect on the immune function of the body, as it can inhibit the differentiation of pro-inflammatory cells such as T helper (Th) 17 cells, thereby reducing the secretion of pro-inflammatory factors such as IL-17 (Murdaca et al., 2011;Yamamoto and Jørgensen, 2020). Therefore, we hypothesize that improving local chronic inflammation in the body may be a potential mechanism for the protective effect of Ruminococcaceae UCG011. ...
Background
Observational studies have hinted at a correlation between the gut microbiota and spinal pain (SP). However, the impact of the gut microbiota on SP remains inconclusive.
Methods
In this study, we employed a two-sample Mendelian randomization (MR) analysis to explore the causal relationship between the gut microbiota and SP, encompassing neck pain (NP), thoracic spine pain (TSP), low back pain (LBP), and back pain (BP). The compiled gut microbiota data originated from a genome-wide association study (GWAS) conducted by the MiBioGen consortium (n = 18,340). Summary data for NP were sourced from the UK Biobank, TSP from the FinnGen Biobank, and LBP from both the UK Biobank and FinnGen Biobank. Summary data for BP were obtained from the UK Biobank. The primary analytical approach for assessing causal relationships was the Inverse Variance Weighted (IVW) method, supplemented by various sensitivity analyses to ensure result robustness.
Results
The IVW analysis unveiled 37 bacterial genera with a potential causal relationship to SP. After Benjamini-Hochberg corrected test, four bacterial genera emerged with a strong causal relationship to SP. Specifically, Oxalobacter (OR: 1.143, 95% CI 1.061–1.232, P = 0.0004) and Tyzzerella 3 (OR: 1.145, 95% CI 1.059–1.238, P = 0.0007) were identified as risk factors for LBP, while Ruminococcaceae UCG011 (OR: 0.859, 95% CI 0.791–0.932, P = 0.0003) was marked as a protective factor for LBP, and Olsenella (OR: 0.893, 95% CI 0.839–0.951, P = 0.0004) was recognized as a protective factor for low back pain or/and sciatica. No significant heterogeneity or horizontal pleiotropy was observed through alternative testing methods.
Conclusion
This study establishes a causal relationship between the gut microbiota and SP, shedding light on the “gut-spine” axis. These findings offer novel perspectives for understanding the etiology of SP and provide a theoretical foundation for potential interventions targeting the gut microbiota to prevent and treat SP.
... Recent studies reported that VD level is directly connected with changes in microbiota composition [67,68]. Furthermore, animal studies found that dietary restriction of VD in mice promotes the increase of Bacteriodetes and Proteobacteria phyla in gut composition [68,69]. ...
... In a contrary study, excess VD intake promotes Prevotella abundance and decreases Haemophilus and Veillonella (Proteobacteria and Firmicutes, phylum, respectively) [67]. Unexpectedly, data about the direct effect of VD on bacteria still needs to be improved; future in vitro studies are recommended to uncover a possible anti-bacterial action of VD. ...
The mucosa of the respiratory system is an essential site for local vitamin D synthesis, degradation, and signaling. It modulates the inflammatory and immune response by saving the integrity of the mucosal barrier and killing the invading pathogen through the induction of antimicrobial peptides. The proper functioning of the immune system within the respiratory system is influenced by the complex interactions of numerous immune pathways, including the gut-lung axis. Recent research has indicated that the gut microbiota is vital in developing and progressing chronic inflammatory chest conditions, such as asthma and chronic obstructive pulmonary disease (COPD). Furthermore, the immune-modulating function of vitamin D operates through the gut mucosa; hence, the vitamin D receptor is expressed to regulate the antimicrobial peptide. The potential protective role of vitamin D and its correlation with COPD has garnered significant interest. It is currently under exploration as a possible adjuvant therapy to aid in managing frequent exacerbation of COPD. In this review, we explored the connection between vitamin D and the immune system, as well as its relationship with microbiota. We also summarized some novel mechanisms of action of vitamin D supplementation that can impact disease exacerbation.
... metabolism pathway (map00051) (Fig 5). Additionally, few metabolites were downregulated in the R isolates and were upregulated in S and B isolates shown to have a role in diminishing the survival of bacteria [31,32]. Vitamin D metabolites [(25R)-1?,25,26-trihydroxy- ...
... Nevertheless, the downregulation of specific metabolites may assist bacteria in dealing with antibiotic stress [73]. Several vitamin D metabolites were shown to be downregulated in R isolates compared to S and B isolates, which have been shown to be significant in reducing bacterial overgrowth in the gut [31,32]. Therefore, it might be suggested that reduction of vitamin D production may enhance survivability of R isolates. ...
In H . pylori infection, antibiotic-resistance is one of the most common causes of treatment failure. Bacterial metabolic activities, such as energy production, bacterial growth, cell wall construction, and cell-cell communication, all play important roles in antimicrobial resistance mechanisms. Identification of microbial metabolites may result in the discovery of novel antimicrobial therapeutic targets and treatments. The purpose of this work is to assess H . pylori metabolomic reprogramming in order to reveal the underlying mechanisms associated with the development of clarithromycin resistance. Previously, four H . pylori isolates were induced to become resistant to clarithromycin in vitro by incrementally increasing the concentrations of clarithromycin. Bacterial metabolites were extracted using the Bligh and Dyer technique and analyzed using metabolomic fingerprinting based on Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (LC-Q-ToF-MS). The data was processed and analyzed using the MassHunter Qualitative Analysis and Mass Profiler Professional software. In parental sensitivity (S), breakpoint isolates (B), and induced resistance isolates (R) H . pylori isolates, 982 metabolites were found. Furthermore, based on accurate mass, isotope ratios, abundances, and spacing, 292 metabolites matched the metabolites in the Agilent METLIN precise Mass-Personal Metabolite Database and Library (AM-PCDL). Several metabolites associated with bacterial virulence, pathogenicity, survival, and proliferation (L-leucine, Pyridoxone [Vitamine B6], D-Mannitol, Sphingolipids, Indoleacrylic acid, Dulcitol, and D-Proline) were found to be elevated in generated resistant H . pylori isolates when compared to parental sensitive isolates. The elevated metabolites could be part of antibiotics resistance mechanisms. Understanding the fundamental metabolome changes in the course of progressing from clarithromycin-sensitive to breakpoint to resistant in H . pylori clinical isolates may be a promising strategy for discovering novel alternatives therapeutic targets.
... Several studies have established a strong correlation between gut microbiota imbalance and susceptibility to immune disorders, as well as the onset of atopic diseases like atopic dermatitis, asthma, and food allergies [20]. Intestinal dysbiosis may cause disorders in regard to intestinal barrier function, which can have a systemic effect on immune function and contribute to the development of immune-mediated pathologies [13,21]. Previous studies have shown that patients with atopic dermatitis and food allergies exhibit an imbalance in their intestinal microbiota. ...
... Changes in the biodiversity of the host-gut microbiome and its metabolic activity have been associated with greater susceptibility to immune-mediated disorders, including allergic diseases [13,21]. The development and balance of the immune system is influenced by interactions between commensal bacteria, intestinal epithelial cells of the host, and immune cells [12,13,20]. ...
The gut microbiota plays an important role in maintaining human health, as well as in the development of various pathologies, as indicated by a large amount of research. One of the manifestations of an imbalance in the gut microbiome composition is the appearance of various diseases or immune reactions, in particular, atopic dermatitis (AD) and/or food allergies (FA). In this research, using 16S NGS sequencing, it was found that the gut microbiome of children with food allergies and children with atopic dermatitis can be characterized as having higher inflammatory potential. Both groups exhibited an abundance of representatives from the Pasteurellaceae and Erysipelotrichaceae families, as well as a decrease in the relative number of representatives from the Barnesiellaceae family compared to healthy participants. In the group of participants with food allergies, there was a decrease in the relative number of Desulfovibrionaceae representatives and Bifidobacteriaceae family enrichment in relatively healthy participants. In addition, when comparing this group with patients with atopic dermatitis, it was revealed that a number of representatives of such families as Erysipelotrichaceae, Ruminococcaceae and Sutterellaceae prevailed. This information confirms that AD and FA correlate with changes in the composition of the gut microbiota. Further research is needed to determine the cause–effect connections and the effect of compounds derived from the microbiota on the AD and FA development and progression, as well as to create new probiotic drugs to prevent and modulate immune responses, including at an early age.
... Vitamin D's role as an antimicrobial is based on its antibacterial peptides, including cathelicidin, β-defensin, and lysozyme, and increased intestinal epithelial macrophage activity. Cathelicidin have antiviral and antifungal properties and it is able to form transmembrane pores in the cell wall of bacteria [26]. In addition, luminal bacteria are constantly exposed to epithelial cells and gastrointestinal tracts' lamina propria [20] -The number of patients with VDD was significantly higher in the rotaviral group than in the control group (after excluding those with an allergic disease). ...
... This study revealed that vitamin D-supplemented porcine has a better food intake, larger body weight, higher intestinal villi, and lower concentration of IL-2, IL-6, and interferon-β [25]. Moreover, significant associations have been found between the microbiome composition and vitamin D. Many studies have also found that the signaling of vitamin D3/VDR can modulate the quantity and distribution of tight junction protein; therefore, decreasing gut permeability and preventing bacterial translocation [26]. Our analysis adds that vitamin D deficiency should be considered as a comorbid that can be present in children with diarrhea in developing countries; thereby focused interventions on both entities should be considered. ...
Introduction
Vitamin D deficiency may increase the risk of childhood diarrhea. We aim to carry out a review and meta-analysis of the evidence relating vitamin D insufficiency to childhood diarrhea.
Methods
We searched PubMed, Ovid, Scopus, and Cochrane Library (from inception to August 2022), then independently reviewed the eligibility, and read full-text reviews for selected articles. Keywords used were ‘vitamin D’, ’25-hydroxyvitamin D’, ‘vitamin D deficiency’, ‘diarrhea’, ‘gastroenteritis’, ‘children’, and ‘pediatric’. The search was limited to studies only in English and with available full-text. Year limitation was not applied in our search. Unpublished trials, dissertations, preliminary reports, conference abstracts, and repositories were excluded from the study. Newcastle-Ottawa Scale was used as the risk of bias assessment tool. Meta-analysis using the random-effects model was done.
Results
Out of 5,565 articles, 12 articles were included in our systematic review, however only 7 articles were eligible for meta-analysis. Meta-analysis showed a statistically significant association between vitamin D deficiency and diarrhea in children in developing countries (OR = 1.79; 95% CI = 1.15 to 2.80; p = 0.01). On the secondary outcome, the association of vitamin D deficiency and duration or recurrences of diarrhea are conflicting.
Conclusions
There is an association between vitamin D deficiency and the prevalence of diarrhea. Future studies should evaluate the causal association, the impact of vitamin D deficiency on the severity of diarrhea, and whether vitamin D deficiency treatments affects the prevalence of diarrhea.
... Several autoimmune diseases tend to share a predisposition to vitamin D deficiency, which might produce an alteration of the microbiome and disrupt the integrity of the intestinal epithelial barrier [18]. It has been also suggested that vitamin D deficiency may play a role in the immune activation of patients with systemic lupus erythematosus, and have an active part in many comorbidities and even complications of this disorder [19]. ...
Background and objective: IgA vasculitis (IgAV), a predominantly pediatric leukocytoclastic disease, has an unpredictable, though largely benign, evolution. The aim of this study was to retrospectively investigate any potential clinical or laboratory predictors of gastrointestinal involvement in a single-center cohort of children with IgAV. Patients and methods: A total of 195 children with a history of IgAV, regularly followed-up for an average period of 1 ± 2.6 years via outpatients clinics of the pediatric rheumatology unit in our University, were assessed, analyzing their clinical and laboratory variables in relationship with their disease evolution and outcome. Results: Univariate analysis showed that a higher neutrophil granulocyte count and lower lymphocyte count (expressed as a percentage of the total white blood cells) were significantly associated with the presence of gastrointestinal involvement at the first examination (65.2 ± 13% versus 58.8 ± 12%, p = 0.02, and 26.4 ± 11% versus 32.1 ± 11%, p = 0.02, respectively). A positive pharyngeal swab for Streptococcus pyogenes, a deficiency of 25-hydroxyvitamin D, a persistence of purpuric rash for more than 1 month, and purpuric lesions in the genital area were also associated with gastrointestinal involvement (p = 0.0001, p = 0.0001, p = 0.007 and p = 0.001, respectively). However, multiple logistic regressions with correction for the patients’ sex and age showed that lower 25-hydroxyvitamin D levels, persistent rash, and genital lesions were independently and significantly associated with signs of gastrointestinal involvement. We then performed a secondary analysis (both univariate and multivariate) to investigate whether vitamin D deficiency was associated with other IgAV manifestations: we found that only 25-hydroxyvitamin D deficiency remained significantly associated with gastrointestinal involvement in IgAV. Conclusions: Patients with IgAV and vitamin D deficiency might be more prone to developing gastrointestinal manifestations of variable severity.
