Mercury and Autistic Gut Disease.

We are challenged to consider the possible role of environmental toxins in autism and other childhood behavioral disorders (1), and creative research in this area surely is warranted (2). Perhaps particular scrutiny should be given to mercury and autism. Many signs and symptoms of mercury exposure correspond to autism (3), and pink disease (acrodynia) from inorganic mercurial teething powders and autism bear strong behavioral resemblance.

Gut disease with inflammation is becoming increasingly evident in autism. Enterocolitis and lymphonodular hyperplasia are found in nearly 90% of regressed autistic children (4). Widespread inflammatory changes with poor intestinal digestive enzyme activity (5), abnormal intestinal permeability (6), and malabsorption (7) have been reported in various autistic subgroups. It would be logical to consider toxins known to cause gut injury when we look for causes of autism.

Inorganic mercurial compounds are notorious for gut injury in humans. In animals, chronic low-nanomolar exposure injures intestinal mucosa (8) and 30-min micromolar exposure injures the colon (9). Also, desposits of antibody in the intestine have resulted from chronic exposure to inorganic mercury (10).

Although systemic passage may be poor, inorganic mercury enjoys avid uptake by the small and large intestines (11). Organic and vapor forms are known to transit membranes quickly and distribute throughout the body, but their excretion is primarily fecal and significantly inorganic, which may affect intestinal residence.

Biliary mercury excretion, predominant in adults, is not achieved in suckling animals and may not exist in infants (12). Ligation of the bile duct of adult animals results in retograde movement of systemic mercury to the feces, emphasizing an excretory role for the intestine (13). Poor biliary excretion in infants might be expected to increase intestinal exposure to mercury. In suckling animals, two-thirds of total ingested inorganic mercury is recoverable after 6 days from gut tissue, particularly the ileum (14).

Worrisome levels of inorganic mercury exist in domestic water supplies (15) and in industrial emissions and municipal sludge widely used as fertilizer on crops (16). Up to 40% of mercury emissions from hydrocarbon combustion and 60% from incinerators is in the inorganic form (17), and mercurial "fall-out" may exceed 1 ppm in soil (18). Individual inorganic mercury ingestion can vary widely and may be greater than expected (19).

Some specifics about autism should heighten interest in mercury. A long clinical tradition has evolved in the use of vitamin [B.sub.6], and its activating enzyme ([B.sub.6]-kinase) is totally inhibited in the intestine at nanomolar concentrations in vitro (20). Organic forms of mercury such as methyl mercury from fish and ethyl mercury as a vaccine preservative (thimersol) may also inflict gut injury. Methyl mercury in primates produces histologic abnormality of one intestinal cell line: Paneth cells are enlarged and packed with secretory granules (21), also specifically reported in autistic children (5).

REFERENCES AND NOTES

(1.) May M. Disturbing behavior: neurotoxic effects in children. Environ Health Perspect 108:A262-A267 (2000).

(2.) Olden K, Guthrie J. Children's health: a mixed review [Editorial]. Environ Health Perspect 108:A250-251 (2000).

(3.) Bernard S, Enayati A, Redwood L, Roger H, Binstock T. Autism: a novel form of mercury poisoning. Med Hypoth 56(4):462-471 (2001).

(4.) Furlano RI, Anthony A, Day R, Brown A, McGarvey L, Thomson MA, Davies SE, Berelowitz M, Forbes A, Wakefield AJ, et al. Colonic CD8 and gamma delta T-cell infiltration with epithelial damage in children with autism. J Pediatr 138:366-372 (2001).

(5.) Horvath K, Papadimitriou JC, Rabsztyn A, Drachenberg C, Tildon JT. Gastrointestinal abnormalities in children with autistic disorder. J Pediatr 135:559-563 (1999).

(6.) 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 85:1076-1079 (1996).

(7.) Goodwin MS, Cowen MA, Goodwin TC. Malabsorption and cerebral dysfunction: a multivariate and comparative study of autistic children. J Autism Child Schizophr 1:48-62 (1971).

(8.) Banerjee S, Bhattacharya S. Histopathological changes induced by chronic nonlethal levels of elsan, mercury, and ammonia in the small intestine of Channa punctatus (Bloch). Ecotoxicol Environ Saf 31:62-68 (1995).

(9.) Bohme M, Diener M, Mestres P, Rummel W. Direct and indirect actions of Hg[Cl.sub.2] and methyl mercury chloride on permeability and chloride secretion across the rat colonic mucosa. Toxicol Appl Pharmacol 114:285-294 (1992).

(10.) Andres P. IgA-IgG disease in the intestine of Brown-Norway rats ingesting mercuric chloride. Clin Immunol Immunopath 30:488-494 (1984).

(11.) Sasser LB, Jarboe GE, Walter BK, Kelman BJ. Absorption of mercury from ligated segments of the rat gastrointestinal tract. Proc Soc Exp Biol Med 157:57-60 (1978).

(12.) Clarkson TW. Personal communication.

(13.) Zalups RK. Intestinal handling of mercury in the rat: implications of intestinal secretion of inorganic mercury following biliary ligation or cannulation. J Toxicol Environ Health 53:615-636 (1998).

(14.) Kostial K, Kargacin B, Landeka M. Gut retention of metals in rats. Biol Trace Elem Res 21:213-218 (1989).

(15.) Mumma RO, Raupach DC, Waldman JP, Tong SS, Jacobs ML, Babish JG, Hotchkiss JH, Wszolek PC, Gutenman WH, Bache CA, et al. National survey of elements and other constituents in municipal sewage sludges. Arch Environ Contamin Toxicol 13:75-83 (1984).

(16.) Wang R, ed. Water Contamination and Health. New York:Marcel Dekker, 1994.

(17.) Chang LW, ed. Toxicology of Metals. Boca Raton, FL:CRC Lewis Press, 1996.

(18.) Windom H. Personal communication.

(19.) Fergusson JE. The Heavy Metals; Chemistry, Environmental Impact, and Health Effects. Oxford, UK:Pergamon Press, 1990.

(20.) Srikantaiah MV, Radhakrishnan AN. Studies on the metabolism of vitamin B6 in the small intestine: Part III--purification and properties of monkey intestinal pyridoxal kinase. Indian J Biochem 7:151-156 (1970).

(21.) Chen W, Body RL, Mottet NK. Biochemical and morphological studies of monkeys chronically exposed to methylmercury. J Toxicol Environ Health 12:407-416 (1983).

Woody R. McGinnis
Tucson, Arizona
E-mail: [e-mail]