Total parenteral nutrition induces a shift in the firmicutes to bacteroidetes ratio in association with paneth cell activation in rats.

C.M.I. Hodin, R.G.J. Visschers, S.S.M. Rensen, B. Boonen, S. Olde Damink, K. Lenaerts*, W.A. Buurman

*Corresponding author for this work

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The use of total parenteral nutrition (TPN) in the treatment of critically ill patients has been the subject of debate because it has been associated with disturbances in intestinal homeostasis. Important factors in maintaining the intestinal homeostasis are the intestinal microbiota and Paneth cells, which exist in a mutually amendable relationship. We hypothesized that the disturbed intestinal homeostasis in TPN-fed individuals results from an interplay between a shift in microbiota composition and alterations in Paneth cells. We studied the microbiota composition and expression of Paneth cell antimicrobial proteins in rats receiving TPN or a control diet for 3, 7, or 14 d. qPCR analysis of DNA extracts from small intestinal luminal contents of TPN-fed rats showed a shift in Firmicutes:Bacteroidetes ratio in favor of Bacteroidetes after 14 d (P < 0.05) compared with the control group. This finding coincided with greater staining intensity for lysozyme and significantly greater mRNA expression of Paneth cell antimicrobial proteins lysozyme (P < 0.05), rat alpha-defensin 5 (P < 0.01), and rat alpha-defensin 8 (P < 0.01). Finally, 14 d of TPN resulted in greater circulating ileal lipid-binding protein concentrations (P < 0.05) and greater leakage of horseradish peroxidase (P < 0.01), which is indicative of enterocyte damage and a breached intestinal barrier. Our findings show a shift in intestinal microbiota in TPN-fed rats that correlated with changes in Paneth cell lysozyme expression (r(s) = -0.75, P < 0.01). Further studies that include interventions with microbiota or nutrients that modulate them may yield information on the involvement of microbiota and Paneth cells in TPN-associated intestinal compromise.
Original languageEnglish
Pages (from-to)2141-2147
JournalJournal of Nutrition
Issue number12
Publication statusPublished - 1 Jan 2012

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