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Gut microbiota interactions with the immunomodulatory role of vitamin D in normal individuals
Affiliation:1. Department of Nutrition, School of Public Health, University of São Paulo, SP, Brazil;2. Oswaldo Cruz Foundation, René Rachou Research Center, Belo Horizonte, MG, Brazil;3. Department of Epidemiology, School of Public Health, University of São Paulo, SP, Brazil;1. Obesity Prevention Program, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA;2. Division of Endocrinology, Boston Children''s Hospital, Boston, MA, USA;3. Department of Medicine, Beth Israel Deaconess Hospital, Boston, MA, USA;4. Environmental Influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of Health, Rockville, MD, USA;5. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA;1. 1st Department of Cardiology, Interventional Electrocardiology, and Hypertension, Jagiellonian University Medical College, Krakow, Poland;2. Chair of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland;1. Department of Pediatrics, University of Virginia, Charlottesville, VA 22908, United States;2. Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, FL 32608, United States;1. Model Systems for Infection and Immunity, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany;2. Institute for Experimental Hematology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany;1. Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, United States, 21225;2. Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, MN, United States;3. Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, United States, 21225;4. Section on Men''s Health, Aging and Metabolism, Brigham and Women''s Hospital Harvard Medical School, Boston, MA, United States, 02115
Abstract:BackgroundDue to immunomodulatory properties, vitamin D status has been implicated in several diseases beyond the skeletal disorders. There is evidence that its deficiency deteriorates the gut barrier favoring translocation of endotoxins into the circulation and systemic inflammation. Few studies investigated whether the relationship between vitamin D status and metabolic disorders would be mediated by the gut microbiota composition.ObjectiveWe examined the association between vitamin D intake and circulating levels of 25(OH)D with gut microbiota composition, inflammatory markers and biochemical profile in healthy individuals.MethodsIn this cross-sectional analysis, 150 young healthy adults were stratified into tertiles of intake and concentrations of vitamin D and their clinical and inflammatory profiles were compared. The DESeq2 was used for comparisons of microbiota composition and the log2 fold changes (log2FC) represented the comparison against the reference level. The association between 25(OH)D and fecal microbiota (16S rRNA sequencing, V4 region) was tested by multiple linear regression.ResultsVitamin D intake was associated with its concentration (r = 0.220, p = 0.008). There were no significant differences in clinical and inflammatory variables across tertiles of intake. However, lipopolysaccharides increased with the reduction of 25(OH)D (p-trend < 0.05). Prevotella was more abundant (log2FC 1.67, p < 0.01), while Haemophilus and Veillonella were less abundant (log2FC ? 2.92 and ? 1.46, p < 0.01, respectively) in the subset with the highest vitamin D intake (reference) than that observed in the other subset (first plus second tertiles). PCR (r = ? 0.170, p = 0.039), E-selectin (r = ? 0.220, p = 0.007) and abundances of Coprococcus (r = ? 0.215, p = 0.008) and Bifdobacterium (r = ? 0.269, p = 0.001) were inversely correlated with 25(OH)D. After adjusting for age, sex, season and BMI, 25(OH)D maintained inversely associated with Coprococcus (β = ? 9.414, p = 0.045) and Bifdobacterium (β = ? 1.881, p = 0.051), but significance disappeared following the addition of inflammatory markers in the regression models.ConclusionThe role of vitamin D in the maintenance of immune homeostasis seems to occur in part by interacting with the gut microbiota. The attenuation of association of bacterial genera by inflammatory markers suggests that inflammation participate in part in the relationship between the gut microbiota and vitamin D concentration. Studies with appropriate design are necessary to address hypothesis raised in the current study.
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