6 -  The brain-gut relationship
Neubürger (1937) described Wernicke's
encephalopathy in three non-alcoholic elderly
patients who suffered chronic gastritis and atrophy of
the lining of the stomach [1].  Neubürger identified
Wernicke's encephalopathy on the basis of multiple
small hemorrhages in the mammillary bodies,
posterior colliculi, and gray matter around the
aqueduct, and suggested "autointoxication" by
products of putrefaction as the cause.  He suggested
a frequent association between intestinal and brain
disorders, distinct from cirrhosis of the liver, but he
proposed several abnormal metabolites in both
conditions that might be toxic.  Neubürger suggested
the intestinal atrophy in his patients was part of a
general "senile atrophy" of other inner organs.

"Liver encephalopathy" (hepatic encephalopathy) is
often part of the terminal illness caused by
alcoholism, a total breakdown of metabolic function
[2].  A mutation in one of the genes that encodes
assembly of the liver enzyme phenylalanine
hydroxylase is the cause of phenylketonuria (PKU).  
This single defective enzyme within the liver produces
abnormal “autotoxic” metabolites that pass into the
brain to impair neurological function and prevent
normal development [3].  Degradation in function of
all the liver's enzymes can result from lifelong
inattention to maintaining good health, especially
when alcohol and other drugs are used in excess.  
The brain may then be flooded with abnormal
metabolites just as deleterious as any produced by
the faulty phenylalanine hydroxylase in PKU.

Degradation of intestinal function can be as
detrimental as liver damage.  Loss of intestinal
function can allow absorption of by-products of partial
digestion that would be excluded by a healthy and
intact intestinal wall.  These by-products will then pass
through the portal vein directly into the liver, and
chronic flooding of the liver with abnormal products of
digestion might be one cause of slow degradation of
liver enzymes.  Such a "leaky gut" hypothesis of
autism has been proposed (D'Eufemia et al 1996)
and has been the topic of informal discussions at
least [4, 5].

Neubürger's ideas about "autointoxicants" are of
interest in light of recent research on gastrointestinal
disorders in some children with autism [6].  Integrity of
intestinal functions in absorption of essential
nutrients, promoting elimination to prevent
putrefaction, and active exclusion of unwanted partial
products of digestion are crucial for maintaining good
health and especially in protecting the brain from toxic
injury.

Full References

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References

1. Neubürger K (1937)
   Wernickesche Krankheit bei
   chronischer Gastritis.  Ein
   Beitrag zu den Beziehungen
   zwischen Magen und
   Gehirn.
   
2. Butterworth RF et al..
   Thiamine-dependent
   enzyme changes in the
   brains of alcoholics:
   relationship to the Wernicke-
   Korsakoff syndrome.
   
3. Guttler F. Phenylketonuria:
   50 years since Folling's
   discovery and still
   expanding our clinical and
   biochemical knowledge.
   
4. D'Eufemia P et al. Abnormal
   intestinal permeability in
   children with autism.
   
5. White JF. Intestinal
   pathophysiology in autism.
   
6. Wakefield AJ et al. The
   significance of ileo-colonic
   lymphoid nodular
   hyperplasia in children with
   autistic spectrum disorder.
   

1. Neubürger K (1937) Wernickesche Krankheit bei chronischer Gastritis.  Ein Beitrag zu
   den Beziehungen zwischen Magen und Gehirn.  Zeitschrift für die gesamte Neurologie
   und Psychiatrie 160:208-225.
   
2. Butterworth RF, Kril JJ, Harper CG. Thiamine-dependent enzyme changes in the brains
   of alcoholics: relationship to the Wernicke-Korsakoff syndrome. Alcohol Clin Exp Res.
   1993 Oct;17(5):1084-8.
   
3. Guttler F. Phenylketonuria: 50 years since Folling's discovery and still expanding our
   clinical and biochemical knowledge. Acta Paediatr Scand. 1984 Nov;73(6):705-16.
   
4. D'Eufemia P, Celli M, Finocchiaro R, Pacifico L, Viozzi L, Zaccagnini M, Cardi E, Giardini
   O. Abnormal intestinal permeability in children with autism. Acta Paediatr. 1996 Sep;85
   (9):1076-9.
   
5. White JF. Intestinal pathophysiology in autism. Exp Biol Med (Maywood). 2003 Jun;228
   (6):639-49.
   
6. Wakefield AJ, Ashwood P, Limb K, Anthony A. The significance of ileo-colonic lymphoid
   nodular hyperplasia in children with autistic spectrum disorder.Eur J Gastroenterol
   Hepatol. 2005 Aug;17(8):827-36.