New intolerances popping up

[faithberry]

I think this is an interesting description of a 'paradox' in gluten-sensitive enteropathy wherein there's an increase in permeability to large molecules and a decrease in permeability to small molecules (like fructose). It may also explain why we have so many problems, although I guess technically gluten-sensitive enteropathy only means celiac.

From the Genova Diagnostics information about their intestinal permeability test:

In certain disease states of the small intestine, such as gluten-sensitive enteropathy, permeability to large molecules may increase while permeability to small molecules decreases.

The explanation of this apparent paradox lies in the different routes of entry for readily absorbed, water-soluble molecules such as mannitol and normally excluded molecules like lactulose. Transcellular uptake of mannitol relies on properties of the luminal cell membrane, a relatively huge area compared to the minute intercellular junctional complexes or “tight junctions.”

Increased porosity of tight junctions has little effect on mannitol uptake, but villous atrophy decreases mannitol diffusion into mucosal cells. Thus, decreased transcellular permeability to small, water-soluble molecules may lead to malnutrition. In contrast, increased porosity of junctional complexes may lead to increased uptake of food antigens and bacterial toxins, correlating with increased susceptibility to food allergies and autoimmune conditions such as rheumatoid arthritis.

I had the test done about four or five years ago, about a year before I had the enterolab testing that showed gluten intolerance. The mannitol uptake was very low, just on the borderline of abnormal so technically still in the reference range. But still that is indicative of poor absorption of small molecules (like fructose). My doctor didn't understand the test and wasn't able to explain it to me properly. So here I am five years later, finally figuring it out!

[ant]

Dear Faith

Increased porosity of tight junctions has little effect on mannitol uptake, but villous atrophy decreases mannitol diffusion into mucosal cells. Thus, decreased transcellular permeability to small, water-soluble molecules may lead to malnutrition. In contrast, increased porosity of junctional complexes may lead to increased uptake of food antigens and bacterial toxins, correlating with increased susceptibility to food allergies and autoimmune conditions such as rheumatoid arthritis.

I may well be barking up the wrong tree here......but do you think that D-mannitol supplement has/could have any effect on the above?

All best, Ant

[tex]

Increased porosity of tight junctions has little effect on mannitol uptake, but villous atrophy decreases mannitol diffusion into mucosal cells. Thus, decreased transcellular permeability to small, water-soluble molecules may lead to malnutrition.

While I agree with the overall concept of their claims, (that opening the tight junctions does not necessarily benefit nutrient absorption, while villus atrophy does indeed diminish nutrient absorption by the enterocytes), I don't see how the claim in the second sentence, (in red, in the above quote), follows from the first observation. Mannitol is most definitely not your typical nutrient. It's a sugar alcohol with special qualities, in fact it's name is derived from the word "manna", (as in manna from heaven). For example, it is used to open the blood-brain barrier, by temporarily shrinking the tightly coupled endothelial cells that make up the barrier, in order to open the junctions between them. That property makes mannitol uniquely valuable for delivering various drugs directly to the brain (for the treatment of Alzheimer's disease, for example).

However, that characteristic, (the ability to shrink endothelial cells, (which are flat epithelial cells that line blood vessels), suggest that it would probably also shrink the enterocytes that comprise the epithelial lining of the intestines), which will naturally decrease the permeability of the enterocytes themselves, and furthermore, shrinking the enterocytes will result in opening the tight junctions. Thus, using mannitol to measure epithelial permeability, obviously will result in a foregone conclusion. Considering those actions, to say that mannitol can be used in permeability experiments, to represent the actions of nutrients, in general, requires a pretty big stretch of the imagination, IMO.

IOW, I think their theory is correct, I just don't believe that they proved their point, because they used "smoke and mirrors" to go about it.

Tex