Abstract
Butyrate produced by the intestinal microbiota is essential for proper functioning of the intestinal immune system. Total dependence on parenteral nutrition (PN) is associated with numerous adverse effects, including severe microbial dysbiosis and loss of important butyrate producers. We hypothesised that a lack of butyrate produced by the gut microbiota may be compensated by its supplementation in PN mixtures. We tested whether i.v. butyrate administration would (a) positively modulate intestinal defence mechanisms and (b) counteract PN-induced dysbiosis. Male Wistar rats were randomised to chow, PN, and PN supplemented with 9 mM butyrate (PN+But) for 12 days. Antimicrobial peptides, mucins, tight junction proteins, and cytokine expression were assessed by RT-qPCR. T-cell subpopulations in mesenteric lymph nodes (MLN) were analysed by flow cytometry. Microbiota composition was assessed in caecum content. Butyrate supplementation resulted in increased expression of tight junction proteins (ZO-1, claudin-7, E-cadherin), antimicrobial peptides (Defa 8, Rd5, RegIIIγ), and lysozyme in the ileal mucosa. Butyrate partially alleviated PN-induced intestinal barrier impairment and normalised IL-4, IL-10, and IgA mRNA expression. PN administration was associated with an increase in Tregs in MLN, which was normalised by butyrate. Butyrate increased the total number of CD4+ and decreased a relative amount of CD8+ memory T cells in MLN. Lack of enteral nutrition and PN administration led to a shift in caecal microbiota composition. Butyrate did not reverse the altered expression of most taxa but did influence the abundance of some potentially beneficial/pathogenic genera, which might contribute to its overall beneficial effect.
Highlights
Parenteral nutrition (PN) represents a life-saving treatment in patients with intestinal failure
Whereas PN alone had no effect, we found significantly increased expression of all three compounds in the PN supplemented with mM butyrate (PN+But) group
Our data show that supplementation of the PN mixture with butyrate is associated with increased Paneth control
Summary
Parenteral nutrition (PN) represents a life-saving treatment in patients with intestinal failure. PN and/or lack of enteral feeding are often associated with serious adverse effects, including impaired mucosal homeostasis, loss of immune reactivity [1], compromised intestinal barrier function, and generalised sepsis [2]. Proper gut barrier function depends on the integrity of physical barriers, i.e., tight junction proteins and adequate mucin production, sufficient production of antimicrobial compounds by Paneth cells and maintaining an optimal. Lack of enteral feeding significantly affects all of these factors. The absence of enteral feeding decreases mRNA and protein expression of typical Paneth cell antimicrobials like lysozyme, cryptdin-4, and secretory phospholipase A2, compromising their function [5, 6]. The data concerning the effect of PN on the function of Paneth cells are inconclusive, as their antimicrobial functions have been shown to both increase [3] and decrease [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
