title: Hepatic Uptake of Rectally Administered Butyrate Prevents an Increase in Systemic Butyrate Concentrations in Humans.
abstract: BACKGROUND
  Short-chain fatty acids (SCFAs), fermentation products of undigested fibers, are considered beneficial for colonic health. High plasma concentrations are potentially harmful; therefore, information about systemic SCFA clearance is needed before therapeutic use of prebiotics or colonic SCFA administration.
  
  
  OBJECTIVE
  The aim of this study was to investigate the effect of rectal butyrate administration on SCFA interorgan exchange.
  
  
  METHODS
  Twelve patients (7 men; age: 66.4 ± 2.0 y; BMI 24.5 ± 1.4 kg/m(2)) undergoing upper abdominal surgery participated in this randomized placebo-controlled trial. During surgery, 1 group received a butyrate enema (100 mmol sodium butyrate/L; 60 mL; n = 7), and the other group a placebo (140 mmol 0.9% NaCl/L; 60 mL; n = 5). Before and 5, 15, and 30 min after administration, blood samples were taken from the radial artery, hepatic vein, and portal vein. Plasma SCFA concentrations were analyzed, and fluxes from portal-drained viscera, liver, and splanchnic area were calculated and used for the calculation of the incremental area under the curve (iAUC) over a 30-min period.
  
  
  RESULTS
  Rectal butyrate administration led to higher portal butyrate concentrations at 5 min compared with placebo (92.2 ± 27.0 μmol/L vs. 14.3 ± 3.4 μmol/L, respectively; P < 0.01). In the butyrate-treated group, iAUCs of gut release (282.8 ± 133.8 μmol/kg BW · 0.5 h) and liver uptake (-293.7 ± 136.0 μmol/kg BW · 0.5 h) of butyrate were greater than in the placebo group [-16.6 ± 13.4 μmol/kg BW · 0.5 h (gut release) and 16.0 ± 13.8 μmol/kg BW · 0.5 h (liver uptake); P = 0.01 and P < 0.05, respectively]. As a result, splanchnic butyrate release did not differ between groups.
  
  
  CONCLUSIONS
  After colonic butyrate administration, splanchnic butyrate release was prevented in patients undergoing upper abdominal surgery. These observations imply that therapeutic colonic SCFA administration at this dose is safe. The trial was registered at clinicaltrials.gov as NCT02271802.
authors.affiliation: Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands; Top Institute Food & Nutrition, Wageningen, Netherlands; and k.vanderbeek@maastrichtuniversity.nl.
authors.forename: Christina M
authors.initials: CM
authors.lastname: van der Beek
authors.affiliation: Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands; Top Institute Food & Nutrition, Wageningen, Netherlands; and.
authors.forename: Johanne G
authors.initials: JG
authors.lastname: Bloemen
authors.affiliation: Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands;
authors.forename: Maartje A
authors.initials: MA
authors.lastname: van den Broek
authors.affiliation: Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands; Top Institute Food & Nutrition, Wageningen, Netherlands; and.
authors.forename: Kaatje
authors.initials: K
authors.lastname: Lenaerts
authors.affiliation: Top Institute Food & Nutrition, Wageningen, Netherlands; and Beneficial Microbes Consultancy, Wageningen, Netherlands.
authors.forename: Koen
authors.initials: K
authors.lastname: Venema
authors.affiliation: Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands;
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
authors.affiliation: Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands; Top Institute Food & Nutrition, Wageningen, Netherlands; and.
authors.forename: Cornelis H
authors.initials: CH
authors.lastname: Dejong
mesh_terms: D000085:Acetates / Q000378:metabolism; D000284:Administration, Oral; D000368:Aged; D015992:Body Mass Index; D002087:Butyrates / Q000008:administration & dosage* / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005232:Fatty Acids, Volatile / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011169:Portal Vein / Q000187:drug effects / Q000378:metabolism; D056692:Prebiotics; D011422:Propionates / Q000378:metabolism
chemical_list: D000085:Acetates; D002087:Butyrates; D005232:Fatty Acids, Volatile; D056692:Prebiotics; D011422:Propionates
keywords: butyrate; gut release; interorgan metabolism; liver metabolism; prebiotics; short-chain fatty acids; splanchnic organs