Variable effects of short chain fatty acids and lactic acid in inducing intestinal mucosal injury in newborn rats.
BACKGROUND
Short chain fatty acids and lactic acid are colonic bacterial fermentation products.


METHODS
To evaluate the effects of these organic acids on the intestinal mucosa, a total of 72 newborn Sprague-Dawley rats (10 days old) were studied. A 3.5F catheter was inserted per rectum 4.0 cm deep into the proximal colon for organic acid administration at a volume of 0.1 ml/10 g body weight. The pH of organic acid solutions and normal saline was adjusted to 4.0. Group 1 (n = 10) received normal saline as a control. Group 2 (n = 11) received 150 mM acetic acid. Group 3 (n = 11) received 300 mM acetic acid. Group 4 (n = 10) received 150 mM butyric acid. Group 5 (n = 11) received 300 mM butyric acid. Group 6 (n = 7) received 150 mM lactic acid, and group 7 (n = 12) received 300 mM lactic acid. Animals were killed 24 hours after colonic installation of test solutions.


RESULTS
Both 300 mM acetic acid and 300 mM butyric acid were associated with impaired weight gain, increased colon wet weight, and increased histologic injury scores in the colon and distal ileum (P < 0.05, analysis of variance). Both 150 mM acetic acid and butyric acid at 150 mmol/L induced minimal injury in the colon and distal ileum. Neither 150 mM nor 300 mM lactic acid induced any identifiable gross or microscopic intestinal mucosal injury.


CONCLUSIONS
Luminal short chain fatty acids can induce dose-dependent intestinal mucosal injury in newborn rats, resembling the pathology seen in neonatal necrotizing enterocolitis. Overproduction/accumulation of short chain fatty acids, but not lactic acid, in the proximal colon and/or distal ileum may play a role in the pathogenesis of necrotizing enterocolitis in premature infants.
Lin
Jing
J
Department of Pediatrics, Mount Sinai School of Medicine, New York, New York 10029, USA. jing.lin@mssm.edu
Nafday
Suhas M
SM
Chauvin
Sara N
SN
Magid
Margret S
MS
Pabbatireddy
Sudha
S
Holzman
Ian R
IR
Babyatsky
Mark W
MW
D019342:Acetic Acid / Q000008:administration & dosage; D000818:Animals; D000831:Animals, Newborn; D020148:Butyric Acid / Q000008:administration & dosage; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005232:Fatty Acids, Volatile / Q000008:administration & dosage*; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D019344:Lactic Acid / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D005232:Fatty Acids, Volatile; D020148:Butyric Acid; D019344:Lactic Acid; D019342:Acetic Acid