PMID: 

Expert Rev Gastroenterol Hepatol. 2019 Nov ;13(11):1039-1048. Epub 2019 Nov 7. PMID: 31657973

Abstract Title: 

Inflammatory bowel diseases: interrelationships between dietary vitamin D, exposure to UV radiation and the fecal microbiome.

Abstract: 

: Environmental factors and an altered fecal microbiome are believed to be central to the pathogenesis of inflammatory bowel diseases (IBD). Vitamin D and ultraviolet radiation (UVR) are environmental factors that are associated by several pathways, including changes to the gastrointestinal microbiome, with the development and course of IBD.: This review explores the interaction of vitamin D, and UVR, with the intestinal innate and adaptive immune systems, and how they may influence the gut microbiome and the subsequent development, and progression, of IBD.: Vitamin D and UVR both regulate innate and adaptive immunity through a combination of common and independent mechanisms, with the overall effect being the promotion of immune tolerance. Vitamin D, and to a lesser extent UVR, can modify the gastrointestinal microbiome either directly, or through immune-mediated mechanisms and this may explain the effect on intestinal inflammation in animal models of IBD and some clinical studies. Thus, both vitamin D and UVR exposure can be considered potential 'master regulators' of gastrointestinal immunity, fine-tuning the complex interaction between genetics, host immunity and the gut microbiome. Further research and increased understanding of environment-host interactions is essential to achieving the ultimate goal of preventing and curing IBD.

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PMID: 

Front Microbiol. 2019 ;10:2410. Epub 2019 Oct 24. PMID: 31708890

Abstract Title: 

Skin Exposure to Narrow Band Ultraviolet (UVB) Light Modulates the Human Intestinal Microbiome.

Abstract: 

The recent worldwide rise in idiopathic immune and inflammatory diseases such as multiple sclerosis (MS) and inflammatory bowel diseases (IBD) has been linked to Western society-based changes in lifestyle and environment. These include decreased exposure to sunlight/UVB light and subsequent impairment in the production of vitamin D, as well as dysbiotic changes in the makeup of the gut microbiome. Despite their association, it is unclear if there are any direct links between UVB light and the gut microbiome. In this study we investigated whether exposing the skin to Narrow Band Ultraviolet B (NB-UVB) light to increase serum vitamin D levels would also modulate the makeup of the human intestinal microbiota. The effects of NB-UVB light were studied in a clinical pilot study using a healthy human female cohort (= 21). Participants were divided into those that took vitamin D supplements throughout the winter prior to the start of the study (VDS+) and those who did not (VDS-). After three NB-UVB light exposures within the same week, the serum 25(OH)D levels of participants increased on average 7.3 nmol/L. The serum response was negatively correlated to the starting 25-hydroxy vitamin D [25(OH)D] serum concentration. Fecal microbiota composition analysis using 16S rRNA sequencing showed that exposure to NB-UVB significantly increased alpha and beta diversity in the VDS- group whereas there were no changes in the VDS+ group. Bacteria from several families were enriched in the VDS- group after the UVB exposures according to a Linear Discriminant Analysis (LDA) prediction, includingFamily, andThe serum 25(OH)D concentrations showed a correlation with the relative abundance of the, specifically members of theandgenera. This is the first study to show that humans with low 25(OH)D serum levels display overt changes in their intestinal microbiome in response to NB-UVB skin exposure and increases in 25(OH)D levels, suggesting the existence of a novel skin-gut axis that could be used to promote intestinal homeostasis and health.clinicaltrials.gov, NCT03962673. Registered 23 May 2019 – Retrospectively registered, https://ift.tt/2xH2DSj.

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PMID: 

Curr Opin Allergy Clin Immunol. 2020 Apr ;20(2):181-187. PMID: 31895129

Abstract Title: 

Vitamin D: can the sun stop the atopic epidemic?

Abstract: 

PURPOSE OF REVIEW: To review recent evidence on the capacity of vitamin D to prevent atopic disease, focussing on food allergy and asthma, and potential underlying mechanisms.RECENT FINDINGS: The incidence of allergic disease continues to increase worldwide. Vitamin D status is influenced by sun exposure and dietary intake. Vitamin D deficiency is linked to an increased incidence of allergic disease and asthma. These associations are generally strongest in early life. The capacity of vitamin D to enhance antimicrobial pathways, promote peripheral immunological tolerance and maintain mucosal barrier integrity may underlie these associations. Interventional studies have addressed the capacity of vitamin D supplementation in utero and early life to reduce the incidence of disease. Ancillary studies have provided insights into potential biological mechanisms linked to these effects.SUMMARY: Observational studies show an inverse association between vitamin D levels and development of food allergy and asthma. Secondary analyses of two recent interventional studies suggest that achieving vitamin D sufficiency throughout pregnancy reduces the incidence of asthma/recurrent wheeze at 3 years. Longitudinal studies of vitamin D requirements in utero and postnatally, better understanding of factors that influence bioavailability of vitamin D and mechanistic insights into vitamin D effects on neonatal-specific immune pathways are awaited.

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PMID: 

Chest. 2017 11 ;152(5):954-962. Epub 2017 Jul 21. PMID: 28739448

Abstract Title: 

Hydrocortisone and Ascorbic Acid Synergistically Prevent and Repair Lipopolysaccharide-Induced Pulmonary Endothelial Barrier Dysfunction.

Abstract: 

BACKGROUND: Sepsis refers to the dysregulated host immune response elicited by microbial infections resulting in life-threatening organ dysfunction. Sepsis represents a medical challenge, since it is associated with a rate of death as high as 60%. Septic shock is strongly associated with vascular dysfunction and elevated pulmonary capillary permeability. We recently reported that the combination of hydrocortisone (HC), ascorbic acid (vitC), and thiamine dramatically improves outcomes and reduces mortality in patients with sepsis. In the present study, we provide experimental evidence in support of the hypothesis that the combination of HC and vitC enhances endothelial barrier function.METHODS: Human lung microvascular endothelial cells were exposed to lipopolysaccharide (LPS) in the absence or presence of HC and vitC.RESULTS: LPS alone induced profound hyperpermeability, as reflected in decreased values of transendothelial electrical resistance. vitC alone did not exhibit barrier enhancement properties nor did it affect the LPS-induced hyperpermeability. Similarly, HC alone exhibited only a minor barrier-enhancing and protective effect. Conversely, the combination of HC and vitC, either as beforeor after treatment, dramatically reversed the LPS-induced barrier dysfunction. The barrier-protective effects of HC and vitC were associated with reversal of LPS-induced p53 and phosphorylated cofilin downregulation and LPS-induced RhoA activation and myosin light chain phosphorylation.CONCLUSIONS: These data provide a novel mechanism of endothelial barrier protection and suggest one possible pathway that may contribute to the therapeutic effects of HC and vitC in patients with sepsis.

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PMID: 

Surg Infect (Larchmt). 2018 Nov/Dec;19(8):812-820. Epub 2018 Jul 24. PMID: 30040533

Abstract Title: 

Patterns of Death in Patients with Sepsis and the Use of Hydrocortisone, Ascorbic Acid, and Thiamine to Prevent These Deaths.

Abstract: 

In general, patients with sepsis die from the host response to the infecting pathogen rather than from the infecting pathogen itself. Four patterns of death have been identified in sepsis, namely vasoplegic shock, single-organ respiratory failure (acute respiratory distress syndrome [ARDS]), multi-system organ failure (MSOF), and persistent MSOF with ongoing inflammation and immunosuppression with recurrent infections (persistent inflammation-immunosuppression and catabolism syndrome [PICS]). To improve the outcome of sepsis adjunctive therapies that modulate the immune system have been tested; these therapies that have targeted specific molecules or pathways have universally failed.We propose that the combination of hydrocortisone, intravenous ascorbic acid, and thiamine (HAT therapy), which synergistically targets multiple pathways, restores the dysregulated immune system and organ injury, and reduces the risk of death and organ failure following sepsis.

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PMID: 

Clin Infect Dis. 2019 Aug 15. Epub 2019 Aug 15. PMID: 31412355

Abstract Title: 

Changes in transcript, metabolite and antibody reactivity during the early protective immune response in humans to Mycobacterium tuberculosis infection.

Abstract: 

BACKGROUND: Strategies to prevent Mycobacterium tuberculosis (Mtb) infection are urgently required. This study aimed to identify correlates of protection against early Mtb infection.METHODS: Two groups of Mtb-exposed contacts of TB patients were recruited and classified according to their Mtb infection status using Tuberculin skin test (TST; cohort 1) or QuantiFERON (QFT; cohort 2. A negative reading at baseline with a positive reading at follow-up classified TST or QFT converters and a negative reading at both time-points classified TST or QFT non-converters. RNA-sequencing, Mtb proteome arrays (IgG and IgA) and metabolic profiling was performed.RESULTS: Several genes were found to be differentially expressed at baseline between converters and non-converters prior to any signs of infection by current tests. Gene set enrichment analysis revealed a distinct B cell gene signature in TST non-converters compared to converters. When infection status was defined by QFT, enrichment of Type I IFN and antiviral gene signatures was observed. A remarkable AUC of 1.0 was observed for IgA reactivity to Rv0134 and an AUC of 0.98 for IgA reactivity to both Rv0629c and Rv2188c. IgG reactivity to Rv3223c resulted in an AUC of 0.96 and was markedly higher compared to TST non-converters. We also identified several differences in metabolite profiles, including changes in biomarkers of inflammation, fatty acid metabolism, and bile acids. Pantothenate (Vitamin B5) was significantly increased in TST non-converters compared to converters at baseline (q=0.0060).CONCLUSIONS: These data provide new insights into the early protective response to Mtb infection and possible avenues to interfere with Mtb infection including Vitamin B5 supplementation.

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PMID: 

Am J Clin Nutr. 1985 Mar ;41(3):578-89. PMID: 3976557

Abstract Title: 

Effects of supplemental pantothenic acid on wound healing: experimental study in rabbit.

Abstract: 

The effect of pantothenic acid supplementation and deficiency on wound healing was investigated over a one month postoperative period in rabbits. The supplemented group was injected with pentothenate (20 mg/kg of body weight/24 h) for three weeks and compared to a placebo group (0.5 ml of distilled water). Deficient animals were fed with a pantothenate free diet also for three weeks. These three experimental groups were matched against a control group. The degree of wound healing was determined by the mean of postoperative breaking strength and wound fibroblast population changes. Pantothenic acid urinary excretion measured by gas chromatography served as control of pantothenate consumption. With regard to these three parameters no significant difference has been found between placebo and controls. The average urinary elimination in the pantothenic acid group was significantly higher as far as the pantothenate supplemented group was concerned, while the deficient group showed no significant decrease when compared to controls. Chronic pre- and postoperative pantothenic acid supplementation significantly increased aponeurosis strength after surgery; it improved slightly, but not significantly the strength of the skin. Furthermore, the fibroblast content of the scar became significantly greater during the fibroblast proliferation phase after pantothenic supplementation. These data suggest that pantothenic acid induces an accelerating effect of the normal healing process. The mechanism responsible for this improvement seems to be an increase in cellular multiplication during the first postoperative period. But the exact intimate mechanism of the beneficial effect of pantothenate remains unclear.

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PMID: 

Phytother Res. 2020 Feb ;34(2):306-314. Epub 2019 Nov 5. PMID: 31691401

Abstract Title: 

The potential role of B5: A stitch in time and switch in cytokine.

Abstract: 

The wound healing process is a multifaceted sequence of activities associated with tissue restoration. Novel approaches for the perfection of wound healing have been determined as a stitch in time saves nine. Dysregulation of the immune response is a key element in the pathogenesis of rheumatic diseases and serves as a potential target for novel therapeutic strategies. Vitamin B5 (VB5), also known as pantothenate or"anti-stress vitamin,"is the precursor of coenzyme A, which is essential in every micro-organism. Many pantothenic acid amides acquire persuasive antimicrobial activity. Pantothenic acid improves surgical wounds healing with moisturizing and skin barrier enhancing potential. Its deficiency leads to reduced cortisol production, increased arthritic pain, myalgia, fatigue, headache, depression, insomnia, and widespread"proinflammatory"effects on the immune-system. VB5 triggers immune cells to produce cytokines and is multifunctional. The paradoxical effect of VB5 on the switch of anti-inflammatory and proinflammatory cytokines has been revealed. This review aims to present the long research journey of B5 as it is becoming a forerunner in the healing of wounds and in enhancing the immune function, thus providing potentially important therapeutic implications. As its role in healing a wound stitch is promising, amending the immune system damage too is a hopeful target.

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PMID: 

Front Immunol. 2018 ;9:1778. Epub 2018 Aug 16. PMID: 30166982

Abstract Title: 

Vitamin B1 Helps to LimitGrowthRegulating Innate Immunity in a Peroxisome Proliferator-Activated Receptor-γ-Dependent Manner.

Abstract: 

It is known that vitamin B1 (VB1) has a protective effect against oxidative retinal damage induced by anti-tuberculosis drugs. However, it remains unclear whether VB1 regulates immune responses during(MTB) infection. We report here that VB1 promotes the protective immune response to limit the survival of MTB within macrophages andthrough regulation of peroxisome proliferator-activated receptorγ (PPAR-γ). VB1 promotes macrophage polarization into classically activated phenotypes with strong microbicidal activity and enhanced tumor necrosis factor-α and interleukin-6 expression at least in part by promoting nuclear factor-κB signaling. In addition, VB1 increases mitochondrial respiration and lipid metabolism and PPAR-γ integrates the metabolic and inflammatory signals regulated by VB1. Using both PPAR-γ agonists and deficient mice, we demonstrate that VB1 enhances anti-MTB activities in macrophages andby down-regulating PPAR-γ activity. Our data demonstrate important functions of VB1 in regulating innate immune responses against MTB and reveal novel mechanisms by which VB1 exerts its function in macrophages.

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PMID: 

BMC Microbiol. 2019 05 22 ;19(1):104. Epub 2019 May 22. PMID: 31117936

Abstract Title: 

The prominent alteration in transcriptome and metabolome of Mycobacterium bovis BCG str. Tokyo 172 induced by vitamin B.

Abstract: 

BACKGROUND: Vitamin B(V) is a crucial dietary nutrient and essential cofactor for several key enzymes in the regulation of cellular and metabolic processes, and more importantly in the activation of immune system. To date, the precise role of Vin Mycobacterium tuberculosis remains to be fully understood.RESULTS: In this study, the transcriptional and metabolic profiles of V-treated Mycobacterium. bovis BCG were analyzed by RNA-sequencing and LC-MS (Liquid chromatography coupled to mass spectrometry). The selection of BCG strain was based on its common physiological features shared with M. tuberculosis. The results of cell growth assays demonstrated that Vinhibited the BCG growth rate in vitro. Transcriptomic analysis revealed that the expression levels of genes related to fatty acid metabolism, cholesterol metabolism, glycolipid catabolism, DNA replication, protein translation, cell division and cell wall formation were significantly downregulated in M. bovis BCG treated with VIn addition, the metabolomics LC-MS data indicated that most of the amino acids and adenosine diphosphate (ADP) were decreased in M. bovis BCG strain after Vtreatment.CONCLUSIONS: This study provides the molecular and metabolic bases to understand the impacts of Von M.bovis BCG.

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