Ever since our first Immunology class, the “old friends”, commensal flora, had caught my attention since they seemed to be able to survive from human immune system’s attack and I was very interested in finding out how they do that. It turned out that this is still a largely unknown question. People agree that the establishment of commensal flora after birth represents a major developmental and functional stimulus to the immune system. The fighting between the immune system and the commensal flora finally creates a mucosal immune homeostasis (1). In addition to stimulate immune system to mature, the “old friends” also support digestion, absorption and metabolism; they compete with pathogens in our intestine for space and resources too (2).
The most interesting thing I found during my web search about commensal flora is a hypothesis on the association between autism and gut dysfunction which could be caused by the altered “old friends”. Autism is a developmental disorder for which there is no drug or even a known cause. One of the hypotheses of its cause is the alteration of gut flora leads to increases in intestinal permeability, also known as “leaky gut” which allows the passage of neuroactive peptides digested from food origin into the blood and then into the cerebrospinal fluid to interfere directly with the function of the CNS (3). In the presence of an alteration of the gut flora, or immune dysregulation, or agenetic predisposition, there is a sustained chronic inflammation and release of calprotectin from neutrophils. The inflammatory response of the intestinal epithelial cells to pathogeneic and altered gut flora can lead to increases in intestinal permeability thus allow the passage of toxins, microbes, undigested food, waste or larger than normal macromolecules (2). Digestion products of natural foods such as cow’s milk and bread are able to enter the blood through the leaky mucosa and induce antigenic responses, as well as interfere directly with the central nervous system. Casomorphins and gliadomorphins are good examples as the short chain neuroactive peptides digested from dietary gluten and casein in the lumen of the small intestine by the action of pancreatic and intestinal peptidases. These peptides, which are structurally similar to endorphins, are called exorphins to reflect their dietary origin (3). Interestingly, a substantial group of autistic children have been diagnosed to have increased intestinal permeability (4, 5).
It seems that the true, unaltered “old friends” are really versatile good friends.
Reference:
1. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=eurekah.section.
2. http://littlecanaries.org/gastro.htm
3. White, JF. Intestinal Pathophysiology in Autism Exp Biol Med (Maywood) 2003, 228, 639–649.
4. Horvath K, Zielke RH, Collins J, et al. Secretin improves intestinal permeability in autistic children. J Pediatr Gastroenterol Nutr 2000;31: S30-31.
5. D'Eufemia P, Celli M, Finocchiaro R, et al. Abnormal intestinal permeability in children with autism. Acta Paediatr 1996;85: 1076-1079.
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7 comments:
In your research did you find what could alter gut flora? I think that it would be interesting to see an actual statistic of how many autistic children have increased intestinal permeability. Also, I wonder about the diet of these children as well as the diet of the mother during her pregnancy.
For your first question. I don't know the exact answer yet. For the diet, there are some parents, doctors and researchers say that children have shown mild to dramatic improvements in speech and/or behavior after gluten and casein were removed from their diet. If you are asking about diet and gut diseases, I don't know much about it. Since the commensal flora were build up after birth. I don't see the direct association between the diet of the pregnant mother and the children's gut diseases.
I was wondering if you found anything about the timing or introduction of gluten and/or casein into an infants diets and alteration of the gut flora? Breastmilk, I believe, is lower in casien than cows milk and goats milk. Do infants that breastfeed have a lower incidence of autism?
Exactly what I was thinking, alisong7630. Would it be suggested then to avoid certain foods in a child's early years, and introduce those foods only after a good base of commensal bacteria has been established to protect the gut?
To my understanding, avoid gluten and/or casein in diet can only alleviate the symptom, but did not cure the disease. It only reduces the amount of exorphins that can get into the blood to interfere with CNS directly. The leaky gut is still there. Rebuild the normal commensal flora in gut is the real therapy based on leaky gut hypothesis.
Very interesting! I've never heard of this hypothesis in relation to autism before. Is this fairly new research? I wonder if there has been any recent advances in understanding the mechanisms.
Very interesting! Ive never known that there was a correlation between altered gut flora and autism. It would be interesting to read any further research on this and whether or not there is a genetic basis on one's susceptibility to have a 'leaky gut'. It would also be fascinating to see the mechanism of how a 'leaky gut' can lead to brain developmental disorders.
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