Vitamin D receptor is overexpressed in the duodenum of patients with irritable bowel syndrome, 2020, Miura et al

[Andy]

Background and Aim

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders and bile acids are thought to be associated with the pathogenesis of IBS. Bile acid receptors are expressed on intestinal epithelial cells. However, no study has assessed bile acid receptor proteins in IBS. Therefore, we examined the intestinal mucosal expression of bile acid receptors in patients with IBS.

Methods
Intestinal biopsies were performed in patients with IBS and controls. Mast cells, vitamin D receptor (VDR), and somatostatin were stained with specific antibodies. Levels of VDR, farnesoid X receptor (FXR), takeda‐G‐protein‐receptor‐5 (TGR5), claudins, and transient‐receptor‐potential‐cation‐channel‐subfamily‐V‐member 6 (TRPV6) were assessed by western blotting.

Results
Mast cell counts in the second part of the duodenum were significantly higher in patients with IBS than in controls. VDR protein levels were significantly elevated in the duodenum and terminal ileum of patients with IBS compared to controls, although this difference was not seen in the cecum or rectum. FXR and TGR5 protein levels did not differ in any part of the intestine. VDR‐positive cryptal epithelia in IBS were distributed not only at basal crypt but also along the upper part of the basal crypt epithelial cells. In contrast, the pattern of gut somatostatin‐positive cells, claudins and TRPV6 levels did not differ.

Conclusions
The number of mast cells in the duodenum was significantly increased, and the protein expression levels of VDR, but not those of FXR or TGR5, were elevated in the duodenal epithelial crypt in patients with IBS.

Paywall, https://onlinelibrary.wiley.com/doi/abs/10.1111/jgh.15225
Sci hub, https://sci-hub.tw/10.1111/jgh.15225

 

[Midnattsol]

They state that the relationship between VDR and Claudin-2 is controversal because it is decreased in the intestine of VDR knockouts but increased in the intestine of VDR knockouts exposed to dextran sodium sulfate? That's two very different states, one with an irritant to the epithelium and one without. Again in cell culture (and possibly rodents, I don't remember), many irritants/barrier disruptors can increase claudin-2 expression and this can be reduced by high levels vitamin D. So quite likely vitamin D have different regulatory action based on the environment.

And no mention of tight junction protein organization, which may also be affected by vitamin D I agree with them we need more studies on how vitamin D can affect epithelial barrier integrity. Preferably also with measurements of vitamin D (I'd like measurements of the active form, although the inactive form is most common. The reason I want the active form is because studies on inflammatory bowel disease patients have shown that some of them have deficiency status of the inactive form, but still high/normal range of the active form).

Edit: Effect of vitamin D on tight junction protein expression might also be affected by overall serum levels of vitamin D, so to be sufficient for the skeletal benefits at 30nmol/L may not be enough for these effects.

 

[spinoza577]

I think this might be worth a thought:

Vitamin D3 transactivates the zinc and manganese transporter SLC30A10 via the Vitamin D receptor.
da Silva et al 2016

from the abstract

In conclusion, we have shown that vitamin D3 transactivates the SLC30A10 gene in a VDR-dependent manner, resulting in increased ZnT10 protein expression. Because SLC30A10 is highly expressed in the small intestine, it is possible that the control of zinc and manganese systemic levels is regulated by vitamin D3 in the intestine. Zinc, manganese and vitamin D are important for bone metabolism and brain health.

The ZnT10 transporter transports Mn and Zn out of the cytoplasma, i.e. out of the cell or into the golgi apparatus. A familiar form of PD has a defect here.

It could mean several things, of course. Maybe there is now too less Zn and Mn in the cytoplasma, or its a counteract upon too much of it, or maybe upon too less VitD, or what else.

 

[Amw66]

I think this might be worth a thought:

Vitamin D3 transactivates the zinc and manganese transporter SLC30A10 via the Vitamin D receptor.
da Silva et al 2016

from the abstract


The ZnT10 transporter transports Mn and Zn out of the cytoplasma, i.e. out of the cell or into the golgi apparatus. A familiar form of PD has a defect here.

It could mean several things, of course. Maybe there is now too less Zn and Mn in the cytoplasma, or its a counteract upon too much of it, or maybe upon too less VitD, or what else.

Would this also affect SODase synthesis and therefore antioxidant levels?

 

[spinoza577]

Would this also affect SODase synthesis and therefore antioxidant levels?

I have been told that nutrition would influence the amount of MnSOD, but I don´t know how good the evidence is. Very interesting, of course. I ever had thought though that this crucial enzym won´t undergo any significant changes under physiological circumstances.

But I Know that in some cancers MnSOD is overexpressed (such has been shown several times) as part of the survival, but in others it seems to be the contrary, here though my reading hasn´t been that good, and I have no literature anyway, and it would be up to you.

There has been one investigation on a plant, and here the authors said, that they have been surprised, that the level of MnSOD came out that independent from enviromental concentrations of this metal.


Interesting could be this, about a blockade of the above mentioned gene:

Epstein-Barr virus encoded EBNA-3 binds to vitamin D receptor and blocks activation of its target genes. Yenamandra et al 2010

Elevated MnSOD has been found several times under acute EBV infection (5-fold rise in Semrau et al 1998), but not so for some other infections known for triggering CFS (same 1998). Ritter 1995 et al found autoantibodies against MnSOD in acute EBV infection.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2191756/ 1995, including a link to 1998.