|Burrin, Douglas - Doug|
Submitted to: American Journal of Physiology - Gastrointestinal and Liver Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/31/2003
Publication Date: 9/11/2003
Citation: Kansagra, K., Stoll, B., Rognerud, C., Niinikoski, H., Ou, C., Harvey, R., Burrin, D.G. 2003. Total parenteral nutrition adversely affects gut barrier function in neonatal piglets. American Journal of Physiology - Gastrointestinal and Liver Physiology. 285:G1162-G1170. Interpretive Summary: Infection is one of the major causes of severe illness in premature infants during the first month of life. Most premature infants are also given nutrition intravenously in the first month of life, because of intestinal problems and poor tolerance to normal oral feeding. Although intravenous nutrition, also called total parenteral nutrition (TPN), is life-saving for these infants, it also has been shown to cause deterioration of some key intestinal functions. One important function of the intestine is to prevent bacteria from entering the body, also called barrier function. However, studies in adult animals suggested that TPN results in increased incidence of infection and this has been linked to deterioration of intestine barrier function. The aim of our study was to establish whether a loss of intestinal barrier function occurs in TPN-fed neonates and if it explained by increased bacterial infection and intestinal permeability. We studied newborn piglets as a model of human infants. We studied piglets fed either by TPN or formula for six days and then measured bacterial infection and intestinal permeability. Our results showed that TPN does result in increased permeability, but not increased bacteria infection, when compared to piglets fed formula enterally. The increased intestinal permeability was associated with deterioration of intestinal structure and increased inflammation. We conclude that TPN is associated with impairment of neonatal gut barrier function as measured by permeability but not translocation. These findings suggest that enteral feeding is important to minimize the incidence of infection in premature infants.
Technical Abstract: Sepsis is the most common morbidity in preterm infants, who often receive total parenteral nutrition (TPN). We hypothesized that gut barrier function is compromised in TPN-fed compared with enterally fed newborn piglets (ENT pigs). Colostrum-deprived newborn pigs were implanted with jugular venous and bladder catheters under general anesthesia. Pigs were either administered TPN (n = 15) or fed formula (ENT pigs, n = 15). After 6 days, pigs were gavaged a solution of mannitol, lactulose, and polyethylene glycol 4000 (PEG 4000) and urine was collected for 24 h. At 7 days, small bowel samples were assayed for myeloperoxidase activity, morphometry, and tight junction protein abundance. Intestinal contents and peripheral organ sites were cultured for bacteria. Urinary recovery (%dose) of mannitol (53 vs. 68) was lower, whereas that of lactulose (2.93 vs. 0.18) and PEG 4000 (12.78 vs. 0.96) were higher in TPN vs. ENT pigs, respectively (P < 0.05). Incidence of translocation was similar in TPN and ENT pigs. Myeloperoxidase activity was increased in TPN vs. ENT pigs in the jejunum (P < 0.001) and was weakly correlated with lactulose (R2 = 0.32) and PEG 4000 (R2 = 0.38) recovery. Goblet cell counts did not change, but intraepithelial lymphocyte numbers decreased with TPN. Only claudin-1 protein abundance was increased in the TPN group. We conclude that TPN is associated with impairment of neonatal gut barrier function as measured by permeability but not translocation.