Feeding autism?

What are those wonky line draw­ings to the left, you ask? They are visual rep­re­sen­ta­tions of four mol­e­cules that Pro­fessor Richard Deth (rhymes with teeth) and his grad stu­dent, Malav Trivedi, think might hold the key to autism.

The one on the far left you’re prob­ably familiar with…although hope­fully not too familiar. BCM-​​7 is a pep­tide (or piece of pro­tein) that is gen­er­ated when the milk pro­tein casein gets digested. As you can see, the ver­sion found in cow’s milk looks a bit dif­ferent from the one found in human milk. α-Gliadin-​​7 is a pep­tide that results from gluten pro­tein digestion.

Now, I’ve always been one to steer clear of gluten and dairy free diet plans. I’m some­thing of bread and butter fiend and the thought of elim­i­nating either from my diet, even if it did make my gut feel better, well…it would make my heart cry a little.

My per­sonal gas­troin­testinal pref­er­ences aside, so-​​called “GFCF” diets (for Gluten Free — Casein Free) are being adopted by many fam­i­lies with autistic chil­dren. Despite the fact that no sta­tis­tical evi­dence has con­firmed a con­nec­tion between gluten or casein and autism, many par­ents say they notice improve­ments in their children’s symp­toms when they elim­i­nate gluten and dairy from the menu.

Deth has long con­sid­ered autism to be a result of oxida­tive stress in the body. While not the main­stream sci­en­tific opinion, Deth’s hypoth­esis is shared by others in the field. “If oxida­tive stress is true,” he said, “per­haps the GF/​CF diet improves things.”

As we talked he pulled out a dia­gram to keep me ori­ented. The first time I looked at this kind of dia­gram I cried (I don’t mean metaphor­i­cally. I really started crying. And then I dropped out of my cell biology class.) So, if this stresses you out half as much as it did the 18 year old me, don’t worry.

Basi­cally that mess up there high­lights a series of bio­log­ical path­ways that have to do with oxida­tive stress. And what does that mean exactly? Basi­cally it’s a state in which a cell has too many reac­tive oxygen species floating around. ROSs as they’re called (not to be con­fused with ROUSs), are mol­e­cules that con­tain oxygen and are ready to go at it with other cru­cial mol­e­cules in the body. Up there in the top right quad­rant of the jumble, you’ll see “GSH” or glu­tathione. This puppy is the holy grail when it comes to get­ting rid of ROSs. If any­thing gets in the way of GSH’s ability to do it’s job, well…oxidative stress persists.

The GSH pro­tein con­tains a whole bunch of the amino acid cys­teine in its struc­ture. So as you can imagine, proper func­tioning of GSH depends on get­ting enough cys­teine into cell. Trivedi’s RISE:2012 work demon­strated that the gluten– and casein– derived pep­tides shown at the top inhibit cys­teine uptake in cells from the human intestinal lining. Inter­est­ingly, the effect was sim­ilar to that of mor­phine and when they blocked opiate recep­tors with another mol­e­cule, the pep­tides no longer got in the way of cys­teine uptake.

The pep­tides also impact another part of the dia­gram above. See where it says “methy­la­tion reac­tions”? Methy­la­tion is a process that turns genes on or off based on both inher­ited and envi­ron­mental fac­tors. It is one of a few bio­log­ical processes col­lec­tively called “epi­ge­netics,” which is any kind of gene reg­u­la­tion that hap­pens out­side of the orig­inal sequence we’re born with. Trivedi showed that methy­la­tion increased when both human and bovine BCM-​​7 entered the pic­ture. Gene expres­sion, on the other hand went down in the case of the bovine pep­tide and up in the human case. All of this indi­cates that there may be a link between the pep­tides, epi­ge­netics, and the oxida­tive state of the cell.

While still very early data, these results could lend insight into the broader bio­log­ical mech­a­nism of autism spec­trum disorders.