Vitamin D Modulates Intestinal Microbiota in Inflammatory Bowel Diseases

Abstract

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. 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). Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and barrier integrity. Vitamin D receptor (VDR) regulates the biological actions of the active VitD (1α,25-dihydroxyvitamin D3), and is involved in the genetic, environmental, immune, and microbial aspects of IBD. 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. Moreover, VDR regulates functions of T cells and Paneth cells and modulates release of antimicrobial peptides in gut microbiota-host interactions. Meanwhile, beneficial microbial metabolites, e.g., butyrate, upregulate the VDR signaling. In this review, we summarize the clinical progress and mechanism studies on VitD/VDR related to gut microbiota modulation in IBD. We also discuss epigenetics in IBD and the probiotic regulation of VDR. Furthermore, we discuss the existing challenges and future directions. There is a lack of well-designed clinical trials exploring the appropriate dose and the influence of gender, age, ethnicity, genetics, microbiome, and metabolic disorders in IBD subtypes. To move forward, we need well-designed therapeutic studies to examine whether enhanced vitamin D will restore functions of VDR and microbiome in inhibiting chronic inflammation.

Inflammatory Bowel Disease and Sarcopenia: Its Mechanism and Clinical Importance

“…There are reports that vitamin D supplementation in pediatric patients with IBD improved bone mineral density and muscle strength [ 113 ], but data in adult patients with IBD are lacking. Vitamin D supplementation in patients with IBD also improves dysbiosis [ 114 ]. VDRs are involved in the regulation of T cell and Paneth cell function and regulate the release of antimicrobial peptides in gut bacteria–host interactions [ 114 ].…”

“…Vitamin D supplementation in patients with IBD also improves dysbiosis [ 114 ]. VDRs are involved in the regulation of T cell and Paneth cell function and regulate the release of antimicrobial peptides in gut bacteria–host interactions [ 114 ]. On the other hand, mucosal healing and disease remission in patients with IBD can significantly improve oral feeding and nutritional status, and prevent muscle loss.…”

Roles of PRR-Mediated Signaling Pathways in the Regulation of Oxidative Stress and Inflammatory Diseases

“…The benefits of the gut microbiota to the host’s physiology include nutrition, immune development, and host defense [ 126 ]. Increasing evidence has shown that some dietary nutrients from environmental factors and PRRs-mediated signaling pathways from host modulate the composition and metabolism of gut microbiota, which influence IBD onset [ 127 , 128 , 129 , 130 , 131 , 132 , 133 ]. Supplementation with 20 mg/kg melatonin (MT) by intraperitoneal injection could downregulate the colon ROS levels, and inhibit the changes of the intestinal microbiota and TLR2/TLR4 activities induced by restraint stress, which together mitigate psychological stress-induced colonic inflammatory responses [ 134 ].…”

Vitamin D and The Gut Microbiota: a Narrative Literature Review

“…In a birth cohort study, prenatal and cord blood vitamin D levels were associated with early life (up to 1 month) gut microbiota [ 36 ]. Recently, a review highlighted the therapeutic potential of vitamin D/VDR in the gut microbiota modulation and anti-inflammatory effects in IBD [ 38 ].…”