Abstract
Gut bacteria have been implicated as an important source of propionate in children with inborn errors of propionate metabolism. We have investigated the value of oral metronidazole (10-20 mg/kg per day) in five children with methylmalonic acidaemia (MMA) and four with propionic acidaemia (PA). Urinary excretion of propionate metabolites fell significantly during the treatment in all subjects, the mean decrease being 41% (range 12-76, P less than 0.01), while mean plasma propionate was reduced from 45.0 mumol/l to 25.1 mumol/l (P less than 0.05). Substantial reduction of the gut bacterial population was confirmed by lactulose breath hydrogen tests and by stool culture, and stool propionate concentration was reduced in most subjects. Clinical improvement was noted in three children. These results suggest that long-term antimicrobial therapy may offer significant clinical benefit to children with inborn errors of propionate metabolism.
MeSH Terms
Amino Acid Metabolism, Inborn Errors/drug therapy
Breath Tests
Child, Preschool
Feces/chemistry,microbiology
Humans
Hydrogen/analysis
Infant
Infant, Newborn
Intestines/microbiology
Methylmalonic Acid/blood
Metronidazole/therapeutic use
Propionates/analysis,blood
Chemicals
Propionates
Metronidazole
Hydrogen
Methylmalonic Acid
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Thompson G N
Nutrition Research Group, Clinical Research Centre, Harrow, UK.
Chalmers R A
Walter J H
Bresson J L
Lyonnet S L
Reed P J
Saudubray J M
Leonard J V
Halliday D
References (13)
13 references, click to expand
-
Contribution of gut bacterial metabolism to human metabolic disease.
Lancet. 1988 May 14;1(8594):1078-9
PMID: 2896913
-
The use of neomycin in the treatment of methylmalonic aciduria.
Pediatrics. 1972 Dec;50(6):925-7
PMID: 4636459
-
A sensitive analytical apparatus for measuring hydrogen production rates. II. Application to studies in human infants.
J Pediatr Gastroenterol Nutr. 1982;1(2):233-7
PMID: 7186035
-
Treatment of diversion colitis with short-chain-fatty acid irrigation.
N Engl J Med. 1989 Jan 5;320(1):23-8
PMID: 2909876
-
Methylmalonic aciduria. An inborn error of metabolism leading to chronic metabolic acidosis.
Arch Dis Child. 1967 Oct;42(225):492-504
PMID: 6061291
-
Metabolic stroke in methylmalonic acidemia.
J Pediatr. 1989 Sep;115(3):499-500
PMID: 2597263
-
Feeding in sheep during intraportal infusions of short-chain fatty acids and the effect of liver denervation.
J Physiol. 1980 Jan;298:407-14
PMID: 7359422
-
Role of anaerobic bacteria in the metabolic welfare of the colonic mucosa in man.
Gut. 1980 Sep;21(9):793-8
PMID: 7429343
-
Influence of ampicillin, clindamycin, and metronidazole on faecal excretion of short-chain fatty acids in healthy subjects.
Scand J Gastroenterol. 1986 Jun;21(5):621-6
PMID: 3749800
-
Influence of oral intake of seven different antibiotics on faecal short-chain fatty acid excretion in healthy subjects.
Scand J Gastroenterol. 1986 Oct;21(8):997-1003
PMID: 3775265
-
Chronic renal failure in methylmalonic acidaemia.
Eur J Pediatr. 1989 Jan;148(4):344-8
PMID: 2707280
-
Measurement of propionate turnover in vivo using sodium [2H5]propionate and sodium [13C]propionate.
Clin Chim Acta. 1989 Jun 30;182(2):141-50
PMID: 2776349
-
Contribution of aminoacid catabolism to propionate production in methylmalonic acidaemia.
Lancet. 1989 Jun 10;1(8650):1298-9
PMID: 2566828