Prolonged <i>Clostridium difficile</i> Infection May Be Associated With Vitamin D Deficiency

Wong, Ken Koon; Lee, Rebecca; Watkins, Richard R.; Haller, Nairmeen

doi:10.1177/0148607114568121

Cited by 10 publications

(7 citation statements)

References 25 publications

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“…g ., peptic ulcer diseases, upper gastrointestinal bleeding, stress ulcer prophylaxis), many of these patients may also be on antibiotics. A known side effect of this treatment is decreased calcium absorption in the small intestine resulting in increased luminal concentrations of calcium [37,38]. In light of our results, it is possible that elevated levels of intestinal Ca 2+ in these individuals allows for more efficient germination of C .…”

Section: Discussionmentioning

confidence: 73%

Intestinal calcium and bile salts facilitate germination of Clostridium difficile spores

et al. 2017

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Clostridium difficile (C. difficile) is an anaerobic gram-positive pathogen that is the leading cause of nosocomial bacterial infection globally. C. difficile infection (CDI) typically occurs after ingestion of infectious spores by a patient that has been treated with broad-spectrum antibiotics. While CDI is a toxin-mediated disease, transmission and pathogenesis are dependent on the ability to produce viable spores. These spores must become metabolically active (germinate) in order to cause disease. C. difficile spore germination occurs when spores encounter bile salts and other co-germinants within the small intestine, however, the germination signaling cascade is unclear. Here we describe a signaling role for Ca2+ during C. difficile spore germination and provide direct evidence that intestinal Ca2+ coordinates with bile salts to stimulate germination. Endogenous Ca2+ (released from within the spore) and a putative AAA+ ATPase, encoded by Cd630_32980, are both essential for taurocholate-glycine induced germination in the absence of exogenous Ca2+. However, environmental Ca2+ replaces glycine as a co-germinant and circumvents the need for endogenous Ca2+ fluxes. Cd630_32980 is dispensable for colonization in a murine model of C. difficile infection and ex vivo germination in mouse ileal contents. Calcium-depletion of the ileal contents prevented mutant spore germination and reduced WT spore germination by 90%, indicating that Ca2+ present within the gastrointestinal tract plays a critical role in C. difficile germination, colonization, and pathogenesis. These data provide a biological mechanism that may explain why individuals with inefficient intestinal calcium absorption (e.g., vitamin D deficiency, proton pump inhibitor use) are more prone to CDI and suggest that modulating free intestinal calcium is a potential strategy to curb the incidence of CDI.

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Section: Discussionmentioning

confidence: 73%

Intestinal calcium and bile salts facilitate germination of Clostridium difficile spores

et al. 2017

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“…Three studies 5 , 6 , 16 assessed the association between 25(OH)D status (<20 ng/mL vs ≥20 ng/mL) and CDI severity (mild vs severe). Finally, 4 studies 5 , 12 , 13 , 16 examined the association between 25(OH)D status (<20 ng/mL vs ≥20 ng/mL) and CDI recurrence (see Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…Among the included studies, 3 reported 25(OH)D concentrations by C difficile diagnosis outcome (infected vs noninfected) 4 , 14 , 15 . Three studies 5 , 6 , 16 assessed the association between 25(OH)D status (<20 ng/mL vs ≥20 ng/mL) and CDI severity (mild vs severe). Finally, 4 studies 5 , 12 , 13 , 16 examined the association between 25(OH)D status (<20 ng/mL vs ≥20 ng/mL) and CDI recurrence (see Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…One possible explanation for this finding may be differences in the duration of follow‐up time used by the researchers. For instance, when CDI recurrence was defined as “within 30 days,” Arramraju et al 12 and Wang et al 13 found a significant association between lower 25(OH)D status and recurrence; however, when CDI recurrence was evaluated in a longer follow‐up period of 56 and 90 days, Abdelfatah et al 5 and Wong et al 16 did not find an association. We must point out, however, that study considerations may have had a role in this discrepancy.…”

Section: Discussionmentioning

confidence: 99%

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25‐Hydroxyvitamin D Concentrations and Clostridium difficile Infection: A Meta‐Analysis

Furuya‐Kanamori

Wangdi

Yakob

et al. 2015

J Parenter Enteral Nutr

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“…D concentrations and acute bacterial diarrhea. Studies in this area are contradictory (19)(20)(21)(22)(23)(24)(25)(26)(27)(28). Bacterial agents are important causes of diarrhea in developing countries (1)(2)(3)(4).…”

Section: Discussionmentioning

confidence: 99%

The Correlation Between Vitamin D and Bacterial Diarrhea in Children

Mahyar

Ayazi

Rad

et al. 2019

Arch Pediatr Infect Dis

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Background: Acute diarrhea is the most common gastrointestinal disease among children. Identification of factors involved in the pathogenesis of acute bacterial diarrhea is highly critical. Objectives: This study was conducted to investigate the correlation between serum 25-hydroxyvitamin D (25 (OH) Vit. D) and acute bacterial diarrhea in children. Methods: The present study compared 60 children with acute bacterial diarrhea (the case group) and 60 healthy children (the control group) for serum 25 (OH) Vit. D concentrations. The children age ranged from two months to 12 years. The serum 25hydroxyvitamin D level was measured using ELISA method. Results: Among 60 children with acute bacterial diarrhea, 38 (63.3%) were males and 22 (36.7%) females. In the control group, 31 (51.6%) were males and 29 (48.4%) females (P = 0.26). The median (IQR) of age in case and control groups were 16 (29) and 16 (24) months, respectively (P = 0.75). The mean ± SD of serum 25 (OH) Vit. D levels in case and control groups were 19.3 ± 7.8 and 22.4 ± 7.3 ng/mL, respectively. There was a significant difference between groups regarding the serum 25 (OH) Vit. D concentrations (P = 0.02). Conclusions: This study revealed a significant correlation between serum 25 (OH) Vit. D level and acute bacterial diarrhea. It is likely that vitamin D plays a role in the pathogenesis of diarrhea.

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Prolonged Clostridium difficile Infection May Be Associated With Vitamin D Deficiency

Abstract: There may be an association between course of diarrhea and increased rate of sepsis in vitamin D-deficient CDI patients.

Cited by 10 publications

References 25 publications

Intestinal calcium and bile salts facilitate germination of Clostridium difficile spores

Intestinal calcium and bile salts facilitate germination of Clostridium difficile spores

25‐Hydroxyvitamin D Concentrations and Clostridium difficile Infection: A Meta‐Analysis

The Correlation Between Vitamin D and Bacterial Diarrhea in Children

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