The effect of butyrate-supplemented parenteral nutrition on intestinal defence mechanisms and the parenteral nutrition-induced shift in the gut microbiota

Butyrateproduced 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 dysbiosisand loss of important butyrateproducers. We hypothesised that a lack of butyrateproduced by the gut microbiota may be compensated by its supplementation in PN mixtures. We tested whether i.v. butyrateadministration would (a) positively modulate intestinal defence mechanismsand (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 junctionproteins 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 caecumcontent. Butyratesupplementation resulted in increased expression of tight junctionproteins (ZO-1, claudin-7, E-cadherin), antimicrobial peptides(Defa 8, Rd5, RegIIIγ) and lysozyme in the ileal mucosa. Butyratepartially 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. Butyrateincreased the total number of CD4+ and decreased a relative amount of CD8+ memory T cellsin MLN. Lack of enteral nutrition and PN administration led to a shift in caecal microbiota composition. Butyratedid 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.