Vitamin D attenuates biofilm-associated infections via immunomodulation and cathelicidin expression: a narrative review

ABSTRACT

Introduction

Infections are becoming more difficult to treat, at least partly on account of microbes that produce biofilms. Reports suggest that decreased levels of antimicrobial peptides like cathelicidin, elevated levels of inflammatory cytokines, and biofilm formation are all associated with vitamin D deficiency, making vitamin D – deficient individuals more susceptible to infection. Infections attributable to biofilm-producing microbes can be managed by adjuvant therapy with vitamin D because of its immunomodulatory role, particularly because of the ability of vitamin D-pathway to induce the antimicrobial peptides like cathelicidin and decrease proinflammatory cytokines.

Areas covered

This narrative review covers biofilm formation, infections associated with biofilm due to vitamin D deficiency, putative role of vitamin D in host protection and the effect of vitamin D supplementation in biofilm-associated infections. A comprehensive literature search in PubMed and Google Scholar utilizing suitable keywords at multiple time points extracted relevant articles

Expert Opinion

Although vitamin D deficiency has been associated with infections by biofilm producing microbes, comprehensive clinical trials in various ethnicities are required to understand the likely relationships between vitamin D receptor gene expression, cathelicidin levels, and infection outcome. Current evidence hypothesizes that maintaining normal vitamin D level can help prevent and treat these infections.

KEYWORDS:

• Antimicrobial peptides
• biofilm-associated infections
• cathelicidin
• immunomodulation
• multi drug resistant species
• vitamin D deficiency
• vitamin D receptor dysregulation
• vitamin D receptor gene expression
• vitamin D supplementation

Article highlights

• Infections are becoming more difficult to treat, partly due to microbes that produce biofilms.

• Decreased levels of antimicrobial peptides like cathelicidin, elevated levels of inflammatory cytokines, and biofilm formation are all associated with vitamin D deficiency, making vitamin D-deficient individuals more susceptible to biofilm-associated infections.

• Much evidence implicates vitamin D’s immunomodulatory role in balancing the proinflammatory and anti-inflammatory aspects of the immune system and attenuating the cytokine storm in such infections.

• There is some evidence that vitamin D adjuvant therapy, in addition to standard care, can improve outcomes because the vitamin D-pathway can significantly increase the expression of antimicrobial peptides (e.g. cathelicidin) during microbial invasion.

• This review chiefly correlates biofilm-associated infections with vitamin D deficiency and collates evidence demonstrating the benefits of adding vitamin D as an adjuvant in the treatment guidelines to manage these types of infections.

Abbreviation

ABPA	=	Allergic bronchopulmonary aspergillosis
ASL	=	Airway surface liquid
CAP	=	Community-acquired pneumonia
CD	=	Cluster of differentiation
COX	=	Cyclooxygenase
CPA	=	Chronic pulmonary aspergillosis
CYP	=	Cytochrome P450
DFU	=	Diabetic foot ulcer
EPM	=	Extracellular polymeric matrix
IFN-γ	=	Interferon-γ
Ig	=	Immunoglobulin
IL-4	=	Interleukin 4
LPS	=	Lipopolysaccharide
MHC	=	Major histocompatibility complex
NETs	=	Neutrophil extracellular traps
OD	=	Once daily
RCT	=	Randomized controlled trial
RTI	=	Respiratory tract infection
RXR	=	Retinoid X receptor
spp	=	Species
TNF	=	Tumor necrosis factor
Th	=	Helper T cells
TLR2	=	Toll like receptor 2
TLRs	=	Toll-like receptors
Treg	=	Regulatory T cells
UTI	=	Urinary tract infections
VDBP	=	Vitamin D binding protein;
VDR	=	Vitamin D receptor;
VDRE	=	Vitamin D response elements

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or mending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.