Calcium Closes Leaky Gut Junctions in Small Intestine - Metabolic Sepsis
CALCIUM OUTSIDE THE CELL NOT INSIDE CELLS
\Excerpted from Susan Owens – Mechanisms of Leaky Gut
LINK - http://lowoxalate.info/papers/mechanisms.html
What have scientists learned about this system of gatekeeping?
I've put a study at the end of this article whose authors discovered that some of this process of opening and closing the tight junctions appeared to be mediated through an interaction with calcium. This did not involve the concentration of calcium that was inside the intestinal cells, but it only involved the calcium that was outside the cell. Removing the calcium from either side of that tight junction could really change things, but changing the level of calcium inside the rectangle (representing the inside of the cell) made no difference at all.
Right next to where that gate is located on the basolateral (or blood side) are some molecules and a "sensor" that picks up calcium that is travelling in the fluid on this basolateral or blood side. I've represented that sensor as an asterisk. If there is adequate calcium at that sensor, then the leaky gut closes, just as if it had been zipped up. In fact, calcium is actually a key ingredient used to close the zipper. When there is not enough calcium present to close the gate, the gate stays open so that calcium from the food side can come in through the gap until there is enough calcium to close the gate again. In fact, at times, there are oscillations that occur as this gate opens and closes in response to calcium.
What happens if the calcium level gets low?
If after the gate opens to let calcium in, there is not enough calcium on the food side to travel through and bind the sensor, then that means there won't be enough calcium to zip up the zipper and close the gate again. The gate will stay open, and until enough calcium comes around to close the gate again, you've got a "leaky gut" that will stay leaky . This means it is important to think about all the circumstances that might cause the supply of calcium to diminish that is travelling from the lumen of the gut or what might cause the calcium on the basolateral side to get low.
What is the connection between calcium and fat maldigestion?
Scientists have figured out that calcium in the lumen can be tied up in fat when one has fat maldigestion and malabsorption. The fat left undigested in the gut binds calcium and makes something of a soap, but this doesn't provide that either the fat or the calcium will get absorbed. This also means that the calcium would fail to make it to the basolateral side when the gate was open, and that would mean the calcium wouldn't be there to interact with the molecules that govern the tight junctions by sensing that there is adequate calcium there. Scientists have done experiments to quantify how this fat effects oxalate absorption, and they also have noted that very often people with celiac disease have this very same maldigestion of fat. This offers one reason people with celiac sprue have a predictable problem with this leaky gut and a condition of excess oxalate absorption that is reflected by high levels of oxalate excretion in the urine called hyperoxaluria.
What is the connection between calcium and oxalic acid that is in the gut?
Undigested fat is not the only way to tie up that needed calcium. Calcium could also be tied up by soluble oxalate that comes from food high in oxalates that were eaten and are present on the inside of the gut.
Food is not the only source of oxalate in the gut. Nature has provided a system to help the body get rid of excess oxalate. Intestinal cells become loaded with oxalic acid when this acid is transferred into them from circulation from the basolateral or blood side, and from there, this acid is actually secreted into the gut. Why does this happen? It is nature's way of ridding the body of a compound that is highly reactive and can be damaging to organs in the body, especially after those organs have already suffered some sort of injury. Oxalates seek injured tissue because they bind to molecules that ordinarily may be hidden from them in healthy tissue.
The secretion of oxalate into the gut happens regardless of the source of those oxalates. That oxalate may have come from the diet, or from chemical or environmental exposure to precursors to oxalate (such as to glycolic acids), or from excess production of oxalates by our own cells due to vitamin deficiency, genetic defect, or some other reason. Scientists have found our bodies make excess oxalate when deficient in vitamin B6, which is a vitamin that has been under a lot of study in autism. Some people may make excess oxalate from an excess of glycine. There are also genetic defects that produce excess oxalate. If there are times when our bodies produce extra oxalates for a good purpose, it has not been discovered yet, but we will be looking for this good purpose in our oxalate project.
One factor that may determine the level of secretion of oxalate into the intestine is its concentration gradient. Oxalate will try and move from places where it is in a higher concentration to places where it is in lower concentration. An excess level of oxalate on the food side of enteric cells may hamper the secretion of oxalates from the blood side. The body may use signals like angiotensin II to step up oxalate secretion from intestinal cells, but sometimes, even though the level in blood might be higher, the secretion may be disrupted by a biochemical signal. This happened experimentally when the signal from angiotensin II was disrupted....something that might happen with an ACE inhibitor or possibly with a chelating agent. More work needs to be done here.
It makes good sense that the body sends excess oxalate to the gut, because the gut is where calcium from the diet could bind the oxalate and that would keep it from being reabsorbed. The oxalate can just stay in the stool in the form of calcium oxalate because it is only the unbound form that is readily absorbed. There are many studies about this.
How do the microbes in the gut affect oxalate absorption?
A different method of reducing oxalate absorption is provided by microbes inside the gut whose role is to eat oxalates and turn them into something else. Unfortunately, these same microbes are easily killed off by antibiotics. Quite a number of studies have found a lack of these specialized bacteria in people who develop oxalate-related health problems. Trying to address this problem, a biotech company is currently working on a probiotic/enzyme formula to "recolonize" the most capable oxalate-eating bacteria, which is oxalobacter formigenes.
The intestines might feel better when the secretion into the gut of oxalic acid is reduced, because research has shown that oxalic acid is by nature corrosive and burning to tissues. Even so, whenever the intestines lose the ability to get rid of "waste" oxalate (using this secretion coupled with binding calcium or being metabolized by oxalate-eating bacteria), then the oxalate remaining in circulation can cause someone to suffer the consequences of having higher levels of oxalic acid reaching other tissues.
What is the role of zonulin in opening up tight junctions?
A study a number of years ago found that the proteins from wheat and corn could induce a leaky gut in rats which had first been made niacin deficient. Since then, other work has found that there is a relationship between exposure to the wheat protein gliadin and the excess production of a talented disrupter of the tight junction called zonulin.
Zonulin is a physiological molecule which was discovered in 2000. Before that discovery scientists had been studying a mimic of this molecule: a toxin produced by a phage that infected a bacteria that could be infecting a human. This toxin was called Zot, and all its talents at disruption of the tight junction came from its being a mimic of zonulin. By watching what Zot did, scientists learned a whole new set of interactions that were governing paracellular transport in the gut.
Zonulin's presence (similar to lack of calcium) opens up the tight junctions between cells. Scientists found that zonulin was elevated both in serum and in the lumen of the gut in celiac disease. They also learned by monitoring people with skin reactions to gluten called dermatitis herpetiformis, that this leaky gut/zonulin phenomenon was a part of the disease process that occurred before the flattening of the villi. They learned that the disruption caused by zonulin could be set in motion by a simple exposure to gliadin.
Apparently, zonulin keeps the gate open. I don't think they've figured out exactly why or how it does that, but this may have to do with the fact that the piece of gluten called gliadin mimics part of a molecule called calreticulin that carries a huge load of calcium.
I don't like the New Age: Things Happen For A Reason; but accept: Chance favors a Prepared Mind.
But then there are times like this when I JUST got done talking to someone about electrolyte imbalance on the topic if the guru-over-sold use of Magnesium which is a calcium antagonist.
Your topic alone spurred my thoughts that for some people the use/over-use of magnesium would cause an osmotic laxative effect pulling water and electrolytes into the gut thus causing dehydration and lack of minerals (including calcium) that could cause muscle spasms/cramps and godnose what else. Folks with constipation rely on magnesium for regular bowel movements but too much of a good thing is bad (ancient chinee saying), yet we all need calcium, however for those with constipation and toxic bowels it can set up your guts like cement and make things insanely worse.
So, I'm thinking there has to be a difference between calcium bound up in food and supplements made from rocks.
There has to be a reason WHY They insisted on SOFTENING water and sold it as a good thing because the major electrolytes of suspended elements are CALCIUM and Magnesium that are substituted for the heart-attack-inducing Sodium during ion-exchange in a softener.
I ceased having problems with oxalates as soon as I went back to the old ways of 50 years ago when we cooked all of our food in HARD WATER that would bind all of the soluble oxalates and take them out of commision.
You, Sir, have a way of pulling back that big log tied with rope that the monks swing to ring the bell.
My head is STILL ringing.
Thank you. Another helpful piece of the puzzle of the leaky gut problem that many peope suffer with.