Selective growth of mucolytic bacteria including Clostridium perfringens in a neonatal piglet model of total parenteral nutrition

BACKGROUND: Compromised barrier function and intestinal inflammation are common complications of total parenteral nutrition (TPN). OBJECTIVE: We tested the hypothesis that the lack of enteral nutrients in TPN might select commensal or pathogenic bacteria that use mucus as a substrate, thereby weakening the protection provided by the intestinal mucus layer. DESIGN: Ileal microbiota profiles of piglets fed by total enteral nutrition (TEN; n = 6) or TPN (n = 5) were compared with the use of 16S ribosomal DNA polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis and with a PCR-based method developed to specifically measure Clostridium perfringens concentrations. Ileal bacteria from TEN and TPN piglets were also examined for their ability to grow on mucin or sulfated monosaccharides. RESULTS: Bacterial community structure was equally complex in the ileum of TEN and TPN piglets, but profiles clustered according to mode of nutrition. Sixty-two percent of total mucus-associated bacteria (100 colonies tested) in TPN compared with 33% of mucus-associated bacteria (100 colonies tested) in TEN ileal samples grew on mucin. Bacteria capable of using sulfated monosaccharides were also enriched in TPN samples. C. perfringens, an opportunistic pathogen, was specifically enriched in the TPN ileum (P < 0.05). These results were corroborated by cultivation-based studies that showed rapid growth of C. perfringens on mucin-based substrates. CONCLUSIONS: Mucolytic potential is widespread among intestinal bacteria. Mucolytic bacteria in general and C. perfringens in particular were selected when enteral nutrients were withheld in this TPN piglet model. Similar enrichment processes may occur in humans nourished by TPN and may thereby contribute to intestinal dysfunction.