The Role of Vitamin D in Reducing Campylobacter jejuni-Induced Colonic Epithelial Apoptosis and Inflammation
Christian Encarnacion
Introduction. Human Campylobacter jejuni infections comprises most bacterial gastrointestinal illnesses worldwide1,2. C. jejuni transmissions are primarily foodborne and sequelae of C. jejuni campylobacteriosis also result in autoimmune diseases such as Guillain-Barre Syndrome1,2. Studies have shown that C. jejuni promotes proinflammatory cytokines that result in debilitating changes to the integrity of the colonic epithelia3,4. Other studies have indicated the anti-inflammatory benefits of vitamin D against C. jejuni infection as well as suppressing epithelial cell apoptosis4,5. Additionally, recent clinical trials have shown that benefits of vitamin D supplementation against gastrointestinal diseases6,7. Methods. An experimental colitis mouse model was utilized to observe inflammatory effects as a result of a gut epithelial vitamin D receptor (VDR) deletion. The efficacy of prophylactic vitamin D treatment four days prior to C. jejuni infection was assessed with an acute campylobacteriosis model. Double-blind placebo-controlled clinical trials were conducted to observe the benefits of vitamin D supplementation in subjects with ulcerative colitis (UC) and intestinal bowel disease (IBD). Results. VDR-deficient mice had more severe diarrhea, higher occurrences of rectal bleeding, and more pronounced ulcerations in the colon4. Epithelial VDR signaling attenuates the PUMA-mediated proapoptotic pathway by blocking NF-κB activation, reducing apoptotic cell bodies and inflammation4,5. Vitamin D also dampens the stimulation of immune cell populations like macrophages and dendritic cells, reducing their pro-inflammatory mediator secretion5. Thus, proinflammatory TNF and IFN–γ concentrations were lower in mice receiving prophylactic vitamin D5. Likewise, UC patients that received treatment of the one-time shot of vitamin D showed markedly reduced levels of IFN–γ and TNF–α6. IBD patients that received vitamin D supplementation showed markedly improved quality of life, as well as reduced frequency and severity of symptoms7. Conclusions. C. jejuni campylobacteriosis promotes proinflammatory cytokines and epithelial cell apoptosis, disrupting the colonic epithelia and resulting in symptoms such as abdominal pain and diarrhea. Vitamin D has been shown to block the PUMA-mediated proapoptotic pathway and reduce inflammation. Clinical trials have proven to be an effective supplement for patients suffering from other gastrointestinal diseases to reduce inflammation and frequency of symptoms.
- Joensen KG, Kiil K, Gantzhorn MR, et al. Whole-genome sequencing to detect numerous campylobacter jejuni outbreaks and match patient isolates to sources, Denmark, 2015-2017. Emerging infectious diseases. 2020;26(3):523-532. https://www.ncbi.nlm.nih.gov/pubmed/32091364. doi: 10.3201/eid2603.190947.
- Davidson AI, Halstead S, Goodfellow JA, et al. Inhibition of complement in Guillain-Barré syndrome: The ICA-GBS study. Journal of the Peripheral Nervous System. 2017;22(1):4-12. https://www.narcis.nl/publication/RecordID/oai:repub.eur.nl:98643. doi: 10.1111/jns.12194.
- Bücker R, Krug SM, Moos V, et al. Campylobacter jejuni impairs sodium transport and epithelial barrier function via cytokine release in human colon. Mucosal Immunology. 2018;11(2):474-485.https://www.ncbi.nlm.nih.gov/pubmed/28766554.doi: 10.1038/mi.2017.66.
- He L, Liu T, Shi Y, et al. Gut epithelial vitamin D receptor regulates microbiota-dependent mucosal inflammation by suppressing intestinal epithelial cell apoptosis. Endocrinology. 2018;159(2):967-979.https://www.ncbi.nlm.nih.gov/pubmed/29228157. doi: 10.1210/en.2017-00748.
- Mousavi S, Lobo de Sá, Fábia Daniela, Schulzke J, Bücker R, Bereswill S, Heimesaat MM. Vitamin D in acute Campylobacteriosis–Results from an intervention study applying a clinical campylobacter jejuni induced enterocolitis model. Frontiers in Immunology. 2019;10.http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=6735268&tool=pmcentrez&rendertype=abstract. doi: 10.3389/fimmu.2019.02094.
- Sharifi A, Vahedi H, Nedjat S, Rafiei H, Hosseinzadeh‐Attar MJ. Effect of single‐dose injection of vitamin D on immune cytokines in ulcerative colitis patients: A randomized placebo‐controlled trial. APMIS. 2019;127(10):681-687. https://onlinelibrary.wiley.com/doi/abs/10.1111/apm.12982. doi: 10.1111/apm.12982.
- Abbasnezhad A, Amani R, Hajiani E, Alavinejad P, Cheraghian B, Ghadiri A. Effect of vitamin D on gastrointestinal symptoms and health‐related quality of life in irritable bowel syndrome patients: A randomized double‐blind clinical trial. Neurogastroenterology & Motility. 2016;28(10):1533-1544. https://onlinelibrary.wiley.com/doi/abs/10.1111/nmo.12851. doi: 10.1111/nmo.12851.