Autism, Digestive Enzymes & Gut Bacteria: Connecting the dots

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I have previously suggested that gut is central to the interaction of genetic and environmental factors involved in diseases like autism and that gastrointestinal alterations provide a unifying framework for understanding the causation of autism.

This recent study provides support to the GUT IS KEY thesis

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It examines the intestinal bacteria adherent to the intestinal wall (bacteria in gut lumen itself as well as those found in feces tend to be different species). In addition, the investigators studied the expression of genes involved in the digestive enzymes in gut.

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A background word about carbohydrate digestion and absorption

Common carbohydrates from diet are digested by disaccharidase enzymes from the small intestinal cells and converted into smaller sugars like glucose for absorption. The absorption occurs with assistance of “transporters”.

Note: Presence of a gene results in deficits/defects if the gene is not expressed in the body. In normal gut with normal expression of digestive enzymes and the transporters, nearly all disaccharidases are well digested and aborbed from gut lumen.

Is It Leaky Gut or Leaky Gut Syndrome?

Significance of study examining gut  bacteria and genes for digestive enzymes

Humans lack certain enzymes that can digest larger carbohydrates (polysaccharides). Bacterial provide enzymes for their digestion enhancing our capacity for carbohydrate digestion and energy extraction. Bacterial fermentation in gut reduces them to short change fatty acids and provide energy for gut wall.

Autism gut-bacteria study investigators

Williams et al from the Center for Infection and Immunitty in Columbia University, New York, Massachussets General Hospital in Boston, MA and Harvard medical school in Boston, MA conducted the study.

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Autism gut-bacteria study

Authors studied 15 autistic children with gastrointestinal problems and compared them to kids with GI problems but without autism.

• Expression of genes related to digestive enzymes (disaccharidases) that are required for absorption of the sugars
• Expression of genes related to the transporters once sugars have been digested by the disaccharidases in the gut.
• Gut bacteria sticking to the gut wall by examining the biopsy specimens to see if there was correlation between the bacteria and the expression of genes.

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Results of autism gut-bacteria study

A. Levels of transcript for digestive enzymes as well as the transporters is reduced in autistic children.

• Over 80% of autistic kids had levels at least 2-fold below the enzyme transcripts levels in controls.
• Over 80% of kids with autism had deficiency in at least one of the two transporters examined.
• 93% of the autistic kids had deficiencies (mRNAs) in atleast one of 5 genes involved in carbohydrate digestion or transport.

B. Bacterial flora adherent to the gut wall is different in autistic kids as compared to controls.

• Bacteriodetes is lower in autism as compared to controls.
• There is significant increase in ratio of Firmicute/Bacteroidete ratio in autism.
• The decrease in Bacteroidetes is associated with firmicutes in autism.
• There is also an increase in Clostridiales/Bacteroidales ratio.

C. Substratification revealed based on timing of onset of onset of gastrointestinal symptoms revealed a significant increase certain species like Clostridiales.

D. Alterations in bacterial flora correlates with deficiencies in digestive enzymes as well as their transporters.

Is It Leaky Gut or Leaky Gut Syndrome?

Conclusions of autism gut-bacteria study

• Kids with autism (atleast a subset) have an intestinal profile of reduced expression of digestive enzymes as well as the transport mechanisms for nutrients.
• The association of these deficits with altered bacterial flora is intriguing (?cause or effect) 

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Dr. Minocha's comments 

• Above findings should be viewed in the context that bacteria-host interactions result in changes throughout the host including immune system, development of the nervous system as well as person's behavior.
• It is not surprising that most medications used in practice have little evidenciary support from scientific literature. 
• This also suggests that a gut-directed multidimentional treatment program is likely to have a greater chance of success in treatment of disorders like autism.

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Wall Street Journal Best Seller Dr. M's Seven-X Plan for Digestive Health