vitamin d, the gut microbiome and inflammatory bowel disease
Anticancer Res 2015;35:1153â60. Mean serum 25(OH)D level was 35.9 nmol/L (norm 50-150nmol/L) in winter (range 5-67, SD 17.5) and 69.6 nmol/L in summer (range 13-119, SD 19.0) (p<0.0005). Their results have shown that, after 6âweek, Crohnâs, Disease Activity Index reduced significantly with. 2017;389:1756–1770. Thus, the vitamin D supplement and activation of VDR could be considered as a multifunctional factor in IBD treatment. Vitamin D has immune modulating effects and normal to high levels might be correlated with less severe Crohn's disease (CD). inîammatory bowel disease: Association with disease activity, Vitamin D concentrations with intestinal but not systemic. In recent years, the immunomodulating effects of vitamin D have gained a huge interest in its possible pathogenic influence on the pathophysiology of IBD. Study demographics are shown in Figure 1. Exp Biol Med (Maywood) 2014;239:1524â30. Colitis was induced in an intestinalâspecific hVDR transgenic model, and the gross manifestation, histological integrity, and intestinal barrier function were tested. IBD include ulcerative colitis (UC), which generally affects only the large intestine mucosa and submucosa, and Crohn’s disease (CD), which may affect any part of the GIT by transmural inflammation. This study explored the effect of intestinal vitamin D signaling on necroptosis and the underlying mechanism in colitis. Bacterial Capnine Blocks Transcription of Human, Antimicrobial Peptides. remain ill-defined. The vitamin D receptor shifts from the nucleus to the cytosol to impede the formation of RIPK1/3. The, nucleotideâbinding oligomerization domainâcontaining, receptor. ratio (NLR) distribution. Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and barrier integrity. There was no significant difference in the seasonal levels of serum 25(OH)D between male and female participants (p=0.601). Moreover, low levels of intestinal epithelial VDR correlated with reduced ATG16L1 and representation by intestinal Bacteroides in patients with IBD. As malnutrition is an important factor in COPD, nutritional support might be a strong component of disease management and prevention. In addition, public data, such as from the ENCODE project, allow to relate the genome-wide actions of VDR and 1,25(OH)2D3 to those of other proteins within the nucleus. However, the precise patterns of composition and functional characteristics of a healthy gut microbiome, Mounting evidence suggests that particular aspects of human health and disease may be attributable to the trillions of microbes that inhabit our gastrointestinal tract, collectively referred to as the gut microbiota. Osteoporosis is a significant social health problem, not only in terms of pain and disability but also in terms of mortality rate. Gentschew L, Ferguson LR. See this image and copyright information in PMC. Although vitamin D, the microbiome and autophagy are all involved in pathogenesis of IBD, it remains unclear whether these processes are related or function independently. The overall probiotic-enhanced âmicrobiome of the ICUâ in Year2 appeared to confer a benefit even to those in Year2 not on probiotics. Conclusion: microbiome, and inîammatory bowel diseases. Analysis of primary tissues obtained from vitamin D3 intervention studies using such markers indicated a large inter-individual variation for the efficiency of vitamin D3 supplementation. Furthermore, we discuss the existing challenges and future directions. Therefore, modifying the diet may prove an easy way to improve the condition and quality of life of neuropsychiatric patients. Vitamin D receptor pathway is required for probiotic protection in colitis. Knee and ankle were the most frequent involved joints. Lithocholic acid (LCA) is a secondary, bile acid that is hepatotoxic and toxic for intestinal cells, and may also induce enteric cancer. The most frequent extraintestinal manifestations in patients with IBD were MSM. clinicians need to know. There have been few clinical trials that have, on the severity (increasing hospitalization and surgery) and, has been reported to cause severe colitis, but in man, it has, not been proven that low serum level of Vitamin D is a. consequence of disease or it is the cause of IBD. dysbiosis and vitamin D deficiency in the pathogenesis of HTN VitD deficiency is correlated with disease activity and its administration targeting a concentration of 30 ng/mL may have the potential to reduce disease activity. The intestinal microbiome is involved in the synthesis of, secondary bile acids. Fecal microbial transplantation from healthy individuals into recipients suffering from diseases related to gut dysbiosis has also been reported to be effective in restoring the normal makeup of gut microbiota, as shown by its efficacy in treating Clostridium difficile infection, colitis, constipation, irritable bowel syndrome, and neurological conditions such as multiple sclerosis and Parkinson's disease. Materials and methods: Furthermore, Vitamin D deficiency leads to dysbiosis of gut microbiome and reported to cause severe colitis. Cantorna MT, McDaniel K, Bora S, Chen J, James J. Vitamin D. disease. 15, ... Vitamin D also stimulates the proliferation of Th2 cells, thus sustaining the production of anti-inflammatory cytokines, and inhibits Th1 and Th17 clones that produce pro-inflammatory cytokines (Bivona, Agnello, and Ciaccio 2018). J Crohns Colitis 2013;7:e665â71. Gastroenterology, Vitamin D and increased risk of cancer in patients with, inflammatory bowel diseases. Suboptimal levels of serum 25(OH)D were found in the majority of our study participants particularly in winter and they would benefit from supplementation. : Vitamin D and inî
ammatory bowel disease, Furthermore, macrophage and dendritic cells (DCs) have, IBD is a more severe disease in children and, Relationship between articular and nonarticular, Pretreatment 25âhydroxyvitamin D levels and durability, Vitamin Dâbinding protein and Vitamin D status of black, Steroid and xenobiotic receptor and Vitamin D receptor, Increasing incidence and prevalence of the, The role of Vitamin D level and related single nucleotide, Synergistic induction of human cathelicidin antimicrobial, Vitamin D receptor as an intestinal bile acid sensor. -, Ungaro R., Mehandru S., Allen P.B., Peyrin-Biroulet L., Colombel J.F. All rights reserved. bowel diseases. increased capacity for energy harvest. We investigated the effects and mechanisms of intestinal epithelial VDR in healthy and inflamed states using cell culture models, a conditional VDR knockout mouse model (VDR(ÎIEC)), colitis models and human samples. Autoimmune diseases such as inflammatory bowel disease (IBD) ... at the beginning and end of the study to track changes to vitamin D levels and gut bacterial ... vitamin D and the microbiome. In regression analysis, oral aphthous (odds ratio [OR] =8.8 [95% confidence intervals (CI), 1.7â45], P = 0.009) and other extraintestinal manifestations (OR = 5.2 [95% CI, 1.3â20], P = 0.02) were significantly related with arthritis. In the brain, vitamin D regulates calcium homeostasis and ion channels (105,106), neurotransmitter levels, including dopamine and serotonin (107)(108)(109)(110), and the secretion of nerve growth factor and BDNF (111,112). We outline a snapshot from a 20-bed ICU in a 300-bed community hospital included patients â¥18 years admitted to the ICU without diarrhea. Background and aim: Hence, further analysis incorporating time in ICU was necessary. 63. Several cell types of the immune system express Vitamin D receptor, and hence the use of V, in immune regulation has some potential. In this review, we summarize the clinical progress and mechanism studies on VitD/VDR related to gut microbiota modulation in IBD. J Nutr, 25 hydroxyvitamin D on bone pathology and disease activity in. One may hypothesize that the use of probiotics in ICU patients in Year2 yielded a microbiome gain, via âmicrobiome cross-talkâ, even to those in Year2 not on probiotics. Evidence suggests that pathologic changes to the microbiota (termed âdysbiosisâ) are associated with a wide variety of medical outcomes, and therefore therapeutic manipulation of the, Background Interestingly, LCA. Musculoskeletal manifestations (MSM) of inflammatory bowel diseases (IBDs) are usually the most frequent extraintestinal manifestations. Nature 2006;444:1027â31. Nutritional psychiatry is in its infancy and more research is needed in this burgeoning low-risk and potentially high-yield field. sensitivity Câreactive protein level and neutrophil to lymphocyte. Several cell types of the immune system express Vitamin D receptor, and hence the use of Vitamin D in immune regulation has some potential. and inflammatory bowel diseases. Blood 2003;102:3314â6. Conclusion: Case-control studies of breast cancer incidence rates provide reliable results. J Biol Chem 1987;262:10931â7. caseâcontrol studies. There is some evidence that Vitamin D can regulate gastrointestinal inflammation, with epidemiological studies showing that individuals with higher serum Vitamin D have a lower incidence of IBD, particularly Crohn's … Prevention and treatment information (HHS). Vitamin D deficiency changes the intestinal microbiome reducing B vitamin production in the gut. We also discuss epigenetics in IBD and the probiotic regulation of VDR. inîammatory bowel disease. Moreover, vitamin D3 positively correlated with HTNâreduced bacterial genera, including Subdoligranulum (R²=0.181, p=0.0023), Ruminiclostridium (R²=0.1217, p=0.014), Intestinimonas (R²=0.2036, p=0.0011), Pseudoflavonifractor (R²=0.1014, p=0.0257), Paenibacillus (R²=0.089, p=0.0373) and Marvinbryantia (R²=0.08173, p=0.0464). J Steroid Biochem, 60. Patients taking vitamin D supplements or with extensive small bowel resection were excluded. Mashhad, Iran. (57.1% females, 42.9% were studied. These insights can be leveraged to define therapeutic targets for restoring VDR expression and function. Clin. Science, induction in T lymphocytes following activation. Vitamin D supplementation is low cost and available and can be a therapeutic option. fatâsoluble vitamins including Vitamin D. Furthermore, disease of the terminal ileum and resection can have an, The interaction of the gut microbiome, the diet, and other, environmental and genetic factors are thought to be. We further discuss the evidence base for six specific nutritional interventions: avoiding artificial sweeteners and gluten, including omega-3 fatty acids and turmeric in the diet, supplementation with vitamin D, and ketogenic diets. The aim of this review is to evaluate the effect of Vitamin D on inflammatory processes, especially its relation to the inflammatory bowel disease (IBD) and gut microbiome. Hostâmicrobiome interactions have been implicated in risk, However, few studies have investigated the association, Health Study has shown that participants in the highest, quartile of Vitamin D had a lower risk of developing CD, but. The minimal concentration of 1 alpha,25-dihydroxyvitamin D3 to induce the cell differentiation was 0.12 nM. We discuss in detail how synaptic pruning is dysregulated differently in the aforementioned neuropsychiatric disorders and how it can be influenced by dysbiosis and/or changes in the intestinal microbiota composition. Geographic patterns of disease onset suggest a role for environmental factors that vary according to latitude. doi: 10.1016/S0140-6736(16)31711-1. In conclusion, a genome-wide (over)view on the genomic locations of VDR provides a broader basis for addressing vitamin D's role in health and disease. Does seasonal level of serum 25-OH vitamin D correlate with the activity of Crohn's disease? In this review, we dissect the link between these neuropsychiatric disorders and the intestinal microbiota by focusing on their effect on synaptic pruning, a vital process in the maturation and establishing efficient functioning of the brain. BALB/C mice weighing between 34 and 35.8 g were divided into 4 groups and placed on daily doses of vitamin D of 3.75 µg (low dose), 7.5 µg (normal dose), and 15 µg (high dose). There is some evidence that Vitamin D can regulate gastrointestinal inflammation, with epidemiological studies showing that individuals with higher serum Vitamin D have a lower incidence of IBD, particularly Crohn's disease. Gut microbiota is a complex ecosystem seen as an extension of human genome. It represents a major metabolic interface of interaction with food components and xenobiotics in the gastrointestinal (GI) environment. A total of 28 patients including 19 ulcerative colitis (UC), 7 Cronh's disease (CD), and two with unclassified colitis with a mean age of 8.3 ± 4.4 years. Regulation of 25âhydroxyvitamin D3â1 alphaâhydroxylase and, production of 1 alpha, 25âdihydroxyvitamin D3 by human. Am J Physiol Gastrointest Liver Physiol. In addition to discovering a link between active vitamin D and overall microbiome diversity, the researchers also noted that 12 particular types of bacteria appeared more often in the gut microbiomes of men with lots of active vitamin D. Most of those 12 bacteria produce butyrate, a beneficial fatty acid that helps maintain gut lining health. In this context, Insulin-Like Growth Factor-1 (IGF-1), vitamin D, serotonin and leptin might play a central role. 2016 Jun 2;12(6):1057-8. doi: 10.1080/15548627.2015.1072670. Lancet. This leads to a shift in the. However, few studies have characterized the underlying interaction between gut microbiota shift and vitamin D3 deficiency in HTN patients. sunscreen use, skin pigmentation, dressing, and latitude. J Clin Invest 2006;116:1703â12. 2020;5:17–30. There is some evidence that Vitamin D can regulate gastrointestinal inflammation. Several potential mechanisms may explain how gut microorganisms could affect bone metabolism, i.e. In this study, … Abstract presentation, Metagenomics, San. Second, the gut microbiota influences at different levels the synthesis, metabolism and transport of FSV including their bioactive metabolites that are either introduced with the diet or released in the gut via entero-hepatic circulation. Gut microbiota are an essential component in the modern concept of human health. number of UC patients compared with CD patients. Unable to load your collection due to an error, Unable to load your delegates due to an error. doi: 10.1016/S1542-3565(17)30640-7. Analysis of Year1 patients and Year2 patients not taking probiotics suggests length of ICU stay significantly impacts diarrhea rates. supplementation in a pilot study of Crohnâs patients. There is, however, a high level of vitamin D deficiency in the Kingdom, comorbid with other disease. Similar results were also detected for NLR (e.g., NLP level was 1.66 ± 0.72 and 1.53 ± 0.67, P = 0.002, before and after therapy with compliance rate of >95.2%). Formaldehyde-assisted isolation of regulatory elements sequencing (FAIRE-seq) data highlight accessible chromatin regions, which are under control of 1,25(OH)2D3. Vitamin D deficiency is frequent among patients with IBD. There is some evidence that Vitamin D can regulate gastrointestinal inflammation, with epidemiological studies showing that individuals with higher serum Vitamin D have a lower incidence of IBD, particularly Crohn's disease. In this perspectives piece, we highlight the roles of the microbiome and inflammation as influencers of anxiety. In recent years, there is an increasing interest in studying the relationship between gut dysmicrobiosis, immune system and bone health, therefore the term "osteomicrobiology" has been recently coined. Conclusion: Vitamin D is necessary for the biosynthesis of cathelicidin (human LL-37), a crucial antimicrobial peptide that is also produced in the gut and linked to the IFN-γ, IL-32, and IL-15 signaling axis. In addition, previous studies have shown that Vitamin D, can aï¬ect the gut microbiome. We also highlight the role of nutrients in altering the tissue microenvironment with lessons from the tumor microenvironment that shapes the quality and quantity of cellular immune responses. in Crohnâs Disease Activity Index scores. can bind to the VDR. In both obesity and IBD, it is of great importance to implement proper dietary ingredients that exert desirable effect on gut microbiota. Consequences of the main genetic variants present in the IBD. Extraintestinal manifestations were determinant variables of arthritis. level of 25 hydroxyvitamin D and duration of responses to, Vitamin D insufficiency and early failure of treatment, did not receive Vitamin D supplements, this failure was. There is plenty of evidence that links vitamin D, the sunshine vitamin, to health outcomes. epithelial Vitamin D receptor deletion leads to defective autophagy. Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract (GIT), including Crohn’s disease (CD) and ulcerative colitis (UC), which differ in the location and lesion extensions. Vitamin D and the vitamin D receptor (VDR) appear to be important immunological regulators of inflammatory bowel diseases (IBD). may be limited by the low number of participants. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e.g., vitamin D hypovitaminosis). Anthropometric and laboratory patient assessment were performed, including the fasting 25-hydroxyvitamin D (25(OH)D). J Clin Endocrinol Metab 2011;96:53â8. Accumulating studies have suggested that gut microbiota (GM) dysbiosis and vitamin D3 deficiency each play an important role during the progression of hypertension (HTN). Results Crohn’s disease; VDR; antimicrobial peptides (AMP); dysbiosis; epigenetics; inflammation; metabolites; microbiome; micronutrient; nuclear receptor; probiotics; tight junctions; ulcerative colitis; vitamin D. The authors declare no conflict of interest. Microbial colonization patterns associated with disease states have been documented with the advancement of sequencing technologies. J Biol Chem, genetic architecture of inflammatory bowel disease. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved. May nutrients and dietary supplements influence the gut-lung microbiota axis in chronic obstructive pulmonary disease and exacerbations? Moreover, it may also be an additional risk factor for vein thromboembolism during the flare. -. Privacy, Help 2020 Jun 26;53(3):33-42. doi: 10.1267/ahc.20011. J Clin Endocrinol. may be affected by outdoor activities, daylight hours. Altogether, the demonstration of the microbiota's influence on brain function via microglialâinduced synaptic pruning addresses the possibility that the manipulation of microbiotaâimmune crosstalk represents a promising strategy for treating neuropsychiatric disorders. The SPT showed CMA in 68.4% (8/17) of UC but none of the CD patients (P = 0.077). the colon tumor necrosis factorâa genes by Vitamin D. The studies support Vitamin D supplementation in IBD, patients. The aim of this review is to evaluate the effect of Vitamin D on inflammatory processes, especially its relation to the inflammatory bowel disease (IBD) and gut microbiome. Vitamin D 3 supplementation was linked to a dose-dependent increase in bacteria associated with decreased inflammatory bowel disease activity. Materials and Methods There is increasing evidence that microbial community structure and diversity are associated with disease severity and clinical outcomes, both in stable chronic obstructive pulmonary disease (COPD) and in exacerbations. barriers. Autophagy. In particular, vitamin D 3 supplementation shows a positive influence on gastrointestinal diseases such as inflammatory bowel disease, infection from bacteria, ... Tabatabaeizadeh et al., indicate that vitamin D deficiency, leading to intestinal dysbiosis, may be a pathogenetic factor in the occurrence of IBD. However, although it is clear that the gut microbiota influences inflammation in the peripheral system, what happens in the lung is still poorly understood. Consequences of the main genetic variants present in the IBD. Please enable it to take advantage of the complete set of features! disease â A randomized doubleâblind placeboâcontrolled study. Dietary supplementation including omega-3 fatty acids and vitamin supplementation, known to have an impact on microbiota composition(Costantini, Molinari, Farinon, & Merendino, 2017;Ribeiro, Nicoli, Santos, & Lima-Santos, 2019; Therapeutic potential of LNA anti-miR-21 in a colon adenocarcinoma for targeting miR-21 expression. Therefore, Vitamin D deîciency can lead to dysbiosis. Our findings may offer some theoretical basis for a novel treatment of IBD in clinical practice. Blood 1991;77:1238â47. Introduction: Environmental factors and an altered fecal microbiome are believed to be central to the pathogenesis of inflammatory bowel diseases (IBD). Genetic factors also have an impact on Vitamin D transport, CD and is also associated with an increased risk of Vitamin, IBD, and body mass index >30 can also lead to Vitamin D, In this study, Web of Science, PubMed, and Google Scholar, have been systematically searched for randomized controlled, studies that investigate the concept of Vitamin D, the gut. Food allergy is frequent in Iranian pediatric IBD patients with CMA being the most common observed allergy. The key to reducing body mass index (BMI) and alleviating the course of IBD is preserving healthy intestinal microflora. 25 hydroxyvitamin D on disease activity of CD patients. These data suggest that Vitamin D is an important factor, in determining the composition of the gut microbiome and, with Vitamin D in IBD because it can regulate homeostasis. Results: I provide evidence that 25(OH)D concentration values are only useful for short follow-up times for breast cancer since it develops rapidly. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e.g., vitamin D hypovitaminosis). Probiotic administration for gut prophylaxis to these high-risk patients remains a heavily investigated topic with no clear-cut guidelines recommendations to date. Overall, taking into account co-founding variables, patients taking probiotics in Year2 had an OR 0.282 [CI 0.112-0.709; p=0.007], indicating a clinically significant decrease in diarrhea of 71.8% versus index Year1 patients not taking probiotics. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e.g., vitamin D hypovitaminosis). However. Vitamin D supplementation is low cost and available and can be a therapeutic option. A complementary approach to medicating symptoms is to address the underlying metabolic pathologies associated with mental illnesses and anxiety. and in some circumstances, higher doses are required. Finally, receiver operating characteristic curve analysis revealed the predictive capacity of differential gut microbiome signatures and decreased vitamin D3 to distinguish HTN patients (AUC=0.749, p=0.006). The targets of vitamin D include macrophages, dendritic cells (DCs), epithelial cells, and T-cells. Ten patients (35.7%) had multiple food allergies (36.8% of UC vs. 42.9% of CD, P > 0.999). In winter 76% of the participants had serum 25(OH)D levels classified as deficient (<50 nmol/L) and all of them had insufficient 25(OH)D levels (<75 nmol/L). Int J Mol Sci. 25-Hydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3 showed only weak inducing activity. Therefore. FOIA Inflammatory bowel disease (IBD) is a chronic disease in the gastrointestinal tract (GIT). This change was associated with. too late to quit? Of those in ICU <2 days, 24% had diarrhea, as compared to 47% having diarrhea if in the ICU >2 days (p=<0.0001). may have an adverse eîect on the course of IBD. The degree of cell differentiation in various markers induced by 12 nM 1 alpha,25-dihydroxyvitamin D3 was nearly equivalent to that induced by 1 microM dexamethasone, the most potent known stimulator. This study demonstrated that obese children and adolescents have significantly lower values of serum 25(OH)D. The positive correlation between vitamin D and PAQ score points to the importance of physical activity in the prevention of further cardiovascular complications and MS. Vitamin D status is closely related to inflammatory bowel disease (IBD), but the mechanism has not been fully elucidated. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e.g., vitamin D hypovitaminosis). Interestingly, this window partly overlaps with the maturation of the intestinal flora (microbiota) that play a critical role in the bidirectional communication between the central and the enteric nervous systems (microbiotaâgutâbrain axis). Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and barrier integrity. J Immunol. This interaction activates the kinase TAK1 and its downstream effectors NF-kB and MAPK, leading to the production of pro-inflammatory cytokines. COVID-19 is an emerging, rapidly evolving situation. GM could have a significant impact on bone metabolism, therefore future clinical studies are necessary to develop a new multidisciplinary approach for osteoporosis treatment and prevention. Chromatin immunoprecipitation sequencing (ChIP-seq) in GM10855 and GM10861 lymphoblastoid cells, undifferentiated and lipopolysaccharide-differentiated THP-1 monocytes, LS180 colorectal cancer cells and LX2 hepatic stellate cells revealed between 1000 and 13,000 VDR-specific genomic binding sites. immune responses especially for innate immune system, and the diversity and the composition of the human, In man, there have been few studies to evaluate the, D for 1 year, reduced the relapse rate from 29% to 13% when, power due to the small sample size. been suggested as an adjunctive treatment in IBD. Intensive care unit (ICU) patients harbor numerous risk factors for microbiome dysbiosis placing them at high risk for diarrhea and C diff colitis. IBD patients often spend less time outdoors because of their, disability. Gastroenterology. Prof. Majid GhayourâMobarhan, Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Tabatabaeizadeh SA, Tafazoli N, Ferns GA, Avan A, GhayourâMobarhan M. Vitamin D, the gut microbiome and inîammatory, . This cross-sectional study aimed to draw a clinical picture of MSM and their relationships with other findings in patients with IBD. There is some evidence that Vitamin D can regulate gastrointestinal inflammation, with epidemiological studies showing that individuals with higher serum Vitamin D … role of the Vitamin D receptor in maintaining the integrity of the, intestinal mucosal barrier. 62, 63 Antibiotics can potentially ameliorate the microbial environment of patients with inflammatory bowel disease, both by decreasing proinflammatory bacteria and by … Vitamin D has an important role in bone metabolism but recently has been recognized as an immunoregulator, and this has led to investigations on the effect of Vitamin D supplementation in various autoimmune diseases and its anti-inflammatory effects. Probiotics remain beneficial for diarrhea prevention in the high-risk ICU patient, and confer a microbiome benefit especially when utilized in those in the ICU>2 days.