Table 3.

Characteristics of Published Clinical Trials Examining Vitamin D and the Microbiota.

Author (Year)	Study Type, Population	Measurements	Results	Conclusion
Sharifi et al. (2016) [17]	Double-blind, randomized, controlled trial with parallel design including UC patients in remission (N = 90)	Serum levels of 25-OHD, PTH, Calcium, ESR, and hs-CRP and cathelicidin expression via qRT-PCR pre and post 90 days of 300,000 IU intramuscular Vitamin D or saline placebo	From pre to post, ↑ 25 -OH D, ↑ hCAP18 (human cationic antimicrobial protein 18) gene expression, ↓ Hs-CRP and ↓ ESR only in Vitamin D group	Supplementation of Vitamin D may benefit UC patients as evidenced by ↓ ESR, ↓ hs-CRP, and ↑ LL37 gene expression
Wu et al. (2015) [96]	C57BL/6 mice and VDR KO C57BL/6 mice; Salmonella-induced colitis mouse model	Salmonella infection Histology, Western blotting; immunofluorescence; VDR protein expression transcriptional activity; RT-PCR	VDR KO mice significantly lost more body weight, probiotics had no protection from Salmonella-induced colitis, and more Salmonella infection occurred compared to VDR+/+ mice; Lactobacillus rhamnosus strain GG (LGG) and Lactobacillus plantarum (LP) ↑ VDR expression in vitro	Probiotics are suggested to enhance VDR expression and may help protect against colitis
Ananthakrishnan et al. (2014) [102]	Multi-institutional cohort of IBD patients (n = 3188); 35 patients developed Clostridium difficile infection (CDI) w/ mean age of 60.5 years old	Serum vitamin D level measurement via radioimmunoassay, high-performance liquid chromatography w/ mass spectrometry	IBD patients with CDI who died had a mean serum average of 12.8 + 8.1 ng/mL compared to IBD patients who remained alive at the end of follow up (24.3 + 13.2 ng/mL); 1 ng/mL increase in serum vitamin D = w/ a 4% CDI reduction	Higher serum vitamin D levels were associated with a decreased CDI risk
Wu et al. (2015) [106]	Conditional VDR KO mouse model (VDRΔIEC) 5% DSS treatment, butyrate treatment (fermentation product of gut microbes)	Vitamin D-responsive element transcriptional activity, Western blotting, intestine histology, immunofluorescence, lysotracker staining, RT-PCR, chromatin immunoprecipitation (CHIP) assay	VDRΔIEC susceptible to DSS-induced colitis, ↓ weight, ↓ cecum length, fecal blood present, ↑ intestinal inflammation, fewer butyrate-producing bacteria and butyrate compared to no DSS treatment; butyrate ↑ VDR expression and inhibited inflammation; ↑ E. coli and Bacteriocides	VDR may help regulate intestinal homeostasis via production of antimicrobial peptides
Lagishetty et al. (2010) [108]	C57BL/6 mice raised on a normal diet (n = 16) or vitamin D-deficient diet (n = 16) × 6 weeks 2.5% DSS treatment	Tissue collection/analysis, clinical colitis score, histological colitis score, flow cytometry, RT-PCR; Ang4 immunohistochemical analysis	Vitamin D-deficient mice treated with DSS had more severe colitis, ↓ colonic Ang4 expression, ↑ bacterial infiltration compared to mice with normal diet; DSS-treated vitamin D-deficient mice had ↓ serum vitamin D level (2.5 ± 0.1 ng/mL) compared to mice with normal diet (24.4 ± 1.8 ng/mL)	Ang4 promotes bacterial innate immunity against gut microbes and its function under a low serum vitamin D levels is impeded
Ooi et al. (2013) [76]	Cyp wild-type mice, Cyp KO mice, VDR wild-type mice, VDR KO mice 3.5% DSS treatment x 5 days	Fecal samples from mice Denaturing gradient gel electrophoresis, metagenomic analysis, RT-PCR, cell isolation	Firmicutes and Bacteroidetes are the dominant phyla in all mice; Cyp KO and VDR KO had ↓ Firmicutes and Deferribacteres, ↑ Proteobacteria and Bacteroidetes phyla than wild-type mice; vitamin D treatment ↓ Helicobacteraceae	Vitamin D and VDR may influence microbiome composition and protect against GI insults
Garg et al. (2018) [98]	Patients with active UC, inactive UC and noninflammatory bowel disease controls; received 40,000 units cholecalciferol weekly for 8 weeks.	Markers of inflammation and fecal microbiota	Patients with active UC ↓ faecal calprotectin levels; this did not change in patients with inactive UC or non-IBD controls. No changes in overall fecal bacterial diversity. were noted although a significant ↑ in Enterobacteriaceae abundance in patients with UC	Vitamin D supplementation reduced intestinal inflammation in patients with active UC, with an increase in Enterobacteriaceae and a trend to reduction in the mucolytic species Ruminococcus gnavus but no change in overall fecal microbial diversity
Schaffler et al. (2018) [111]	A prospective, longitudinal, controlled interventional analysis in seven patients with Crohn’s disease (CD) in clinical remission and 10 healthy controls (HC); orally administration of vitamin D	Intestinal bacterial composition	↓ bacterial richness in the CD microbiome. ↑ Alistipes, Barnesiella, unclassified Porphyromonadaceae (both Actinobacteria), Roseburia, Anaerotruncus, Subdoligranulum and an unclassified Ruminococaceae (all Firmicutes)	Vitamin D has a specific influence on the bacterial communities in CD, but not in HC. Administration of vitamin D may have a positive effect in CD by modulating the intestinal bacterial composition and also by increasing the abundance of potential beneficial bacterial strains. Vitamin D did not change the bacterial communities in HC.