I was excited to read this paper and congratulate the authors on its publication. I encourage the authors to consider the model of disaccharidase deficiency described in Elaine Gottschall's 1994 book "Breaking the Vicious Cycle." Ms. Gottschall's model is similar to the one proposed in the PLoS article.

For example, in the PLoS One article's Discussion on page 11, it states:

"Based on these findings, we propose a model whereby deficiencies in disaccharidases and hexose transporters alter the milieu of carbohydrates in the distal small intestine (ileum) and proximal large intestine (cecum), resulting in the supply of additional growth substrates for bacteria. These changes manifest in significant and specific compositional changes in the microbiota of AUT-GI children (see Figure 7A–C)"

"Breaking the Vicious Cycle" describes a similar process of deficiencies in disaccharidase (but not hexose transporters) in detail. As a minimal example, below are the labels from Figure 8 on page 24 of Breaking the Vicious Cycle:

"Dietary disaccharides -> Injured and blunted microvilli with few or no enzymes -> Undigested disaccharides remain in intestine"

On page 26, Ms. Gottschall describes these undigested disaccharides further:

"The sugars, then, remain undigested in the small intestine. Their presence in the lumen of the intestine causes a reversal of the normal nutrition process. Instead of nutrients flowing from the intestinal space into the bloodstream, water is drawn into the intestinal lumen. The water, carrying nutrients, is lost in abnormal intestinal function (diarrhea) and the cells of the body are deprived of energy, minerals, and vitamins. Most seriously, the sugars remaining in the intestinal lumen provide energy for further microbial fermentation and the growth of intestinal microbes." [boldface added]

The boldfaced part of this last paragraph agrees with the PLoS One authors' recent proposal describing undigested carbohydrates in the intestine "resulting in the supply of additional growth substrates for bacteria."

Chapter 4, titled "Breaking the Vicious Cycle" [same name as the book] describes this process in detail describing how small intestinal mucosa injury leads to carbohydrate malabsorption, an increase in harmful metabolic by-products, further carbohydrate malabsorption, bacterial overgrowth, diarrhea, and potentially abnormal brain function and behavior.

Based on the Ms. Gottschall's model, as well as her proposed diet to alleviate the dysbiosis due to undigested carbohydrates, Rush Medical Center in Chicago is currently conducting a study on inflammatory bowel disease titled: "The Specific Carbohydrate Diet: Does it change the intestinal microbiota and metabolome?"

In addition, since speaking at an autism conference in 2004 Ms. Gottschall's work has been widely distributed within the autism community. Although Ms. Gottschall passed away in 2005, at the of 84, her book continues to sell strongly on amazon.

It should be noted that Ms. Gottschall held a Master's degree awarded by a Cell Science department in Western Ontario. As a result, her book extensively cites the research available at the time of the book's publication and reprints.

At least one recent autism article cites the book.

In June of 2011, the journal Nutrition Research published an article titled "B vitamin supplementation reduces excretion of urinary dicarboxylic acids in autistic children." In the introduction of that article the authors credit Breaking the Vicious Cycle when listing metabolic disorders seen in children with autism including "chronic constipation, periods of diarrhea, abdominal pain, and indications of intestinal bacterial and fungal overgrowth." [boldface added]

It may be helpful to investigate Ms. Gottschall's model further as there are several clinicians that use this model when considering treatment for autism as well as inflammatory bowel disease as well as autism.

Thank you for your time.

Raman Prasad



Notes:

- Quotes from Breaking the Vicious Cycle are from a 1994 edition
- Starting in 2004, editions of Breaking the Vicious Cycle included a chapter on autism.
- Rush medical center study: http://www.rush.edu/rumc/...
- pubmed link for "B vitamin supplementation reduces excretion of urinary dicarboxylic acids in autistic children": http://www.ncbi.nlm.nih.g...
- In 2004 and 2005, Ms. Gottschall spoke at 3 DAN (Defeat Autism Now) conferences. Although an alternative conference, at least one of the article's authors has spoken at this conference on multiple occasions.
- Amazon.com link for Breaking the Vicious Cycle: http://www.amazon.com/Bre... includes 303 reviews