Short chain fatty acids exchange across the gut and liver in humans measured at surgery

  • Johanne G. Bloemen
    Affiliations
    Department of Surgery, Nutrition and Toxicology Research Institute Maastricht, Maastricht University Medical Centre, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands
    Search for articles by this author
  • Koen Venema
    Affiliations
    Ti Food and Nutrition, PO Box 557, 6700 AN, Wageningen, The Netherlands
    Search for articles by this author
  • Marcel C. van de Poll
    Affiliations
    Department of Surgery, Nutrition and Toxicology Research Institute Maastricht, Maastricht University Medical Centre, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands
    Search for articles by this author
  • Steven W. Olde Damink
    Affiliations
    Department of Surgery, Nutrition and Toxicology Research Institute Maastricht, Maastricht University Medical Centre, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands
    Search for articles by this author
  • Wim A. Buurman
    Affiliations
    Department of Surgery, Nutrition and Toxicology Research Institute Maastricht, Maastricht University Medical Centre, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands
    Search for articles by this author
  • Cornelis H. Dejong
    Correspondence
    Correspondence to: Cornelis H. Dejong, University Hospital Maastricht, Department of Surgery, PO Box 5800, 6200 AZ, Maastricht, The Netherlands. Tel.: +31 43 3871494, fax: +31 43 3875473.
    Affiliations
    Department of Surgery, Nutrition and Toxicology Research Institute Maastricht, Maastricht University Medical Centre, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands
    Search for articles by this author

      Summary

      Background & aims

      Short chain fatty acids (SCFAs; acetate, propionate and butyrate) are important energy sources for colonocytes and are assumed to play a key role in gut health. Local effects of SCFAs have been investigated, but less is known about whole body metabolism of these SCFAs. The aim of the present study was to quantify the role of the gut and liver in interorgan exchange of SCFAs in humans in vivo.

      Methods

      Twenty-two patients undergoing major upper abdominal surgery were studied. Blood was sampled from a radial artery, the portal and a hepatic vein. Portal, splanchnic and arterial blood flow was measured using intra-operative Duplex ultrasonography. SCFAs were measured on a liquid chromatography system combined with mass spectrometry.

      Results

      SCFAs were released by the gut, 34.9 (9.1) μmolkg bodyweight−1h−1. SCFAs uptake by the liver was significant for propionate and butyrate; −5.6 (1.3) and −3.8 (1.6) μmolkg bodyweight−1h−1 (p=0.0002 and p=0.03) respectively and counterbalanced gut release. Liver uptake of acetate was not significant, −5.2 (6.6) μmolkg bodyweight−1h−1 (p=0.434). Splanchnic (i.e., gut+liver) SCFAs release was significant for acetate and propionate, 17.3 (7.3) and 1.2 (0.4) μmolkg bodyweight−1h−1 (p=0.027 and p=0.0038), respectively. Splanchnic release of butyrate was not significantly different from zero (1.9 (1.2) μmolkg bodyweight−1h−1, p=0.129). BMI and previous colonic resection did not affect gut release of SCFAs.

      Conclusion

      This is the first in vivo study on the role of the gut and liver in SCFAs exchange in humans in vivo. It is shown that intestinal SCFAs release by the gut is equalled by hepatic uptake.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and Personal
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Nutrition
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Macfarlane S.
        • Macfarlane G.T.
        • Cummings J.H.
        Review article: prebiotics in the gastrointestinal tract.
        Aliment Pharmacol Ther. 2006; 24: 701-714
        • Topping D.L.
        • Clifton P.M.
        Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides.
        Physiol Rev. 2001; 81: 1031-1064
        • Knudsen K.E.B.
        Effect of dietary non-digestible carbohydrates on the rate of SCFA delivery to peripheral tissues.
        Food Ingred J Jpn. 2005; 210: 1008-1017
        • Cook S.I.
        • Sellin J.H.
        Review article: short chain fatty acids in health and disease.
        Aliment Pharmacol Ther. 1998; 12: 499-507
        • Kristensen N.B.
        • Harmon D.L.
        Effect of increasing ruminal butyrate absorption on splanchnic metabolism of volatile fatty acids absorbed from the washed reticulorumen of steers.
        J Anim Sci. 2004; 82: 3549-3559
        • Wachtershauser A.
        • Stein J.
        Rationale for the luminal provision of butyrate in intestinal diseases.
        Eur J Nutr. 2000; 39: 164-171
        • Welters C.F.
        • Heineman E.
        • Thunnissen F.B.
        • van den Bogaard A.E.
        • Soeters P.B.
        • Baeten C.G.
        Effect of dietary inulin supplementation on inflammation of pouch mucosa in patients with an ileal pouch-anal anastomosis.
        Dis Colon Rectum. 2002; 45: 621-627
        • Welters C.F.
        • Deutz N.E.
        • Dejong C.H.
        • Soeters P.B.
        • Heineman E.
        Supplementation of enteral nutrition with butyrate leads to increased portal efflux of amino acids in growing pigs with short bowel syndrome.
        J Pediatr Surg. 1996; 31: 526-529
        • Finney M.
        • Smullen J.
        • Foster H.A.
        • Brokx S.
        • Storey D.M.
        Effects of low doses of lactitol on faecal microflora, pH, short chain fatty acids and gastrointestinal symptomology.
        Eur J Nutr. 2007;
        • Tedelind S.
        • Westberg F.
        • Kjerrulf M.
        • Vidal A.
        Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: a study with relevance to inflammatory bowel disease.
        World J Gastroenterol. 2007; 13: 2826-2832
        • Manns J.G.
        • Boda J.M.
        Insulin release by acetate, propionate, butyrate, and glucose in lambs and adult sheep.
        Am J Physiol. 1967; 212: 747-755
        • Feliz B.
        • Witt D.R.
        • Harris B.T.
        Propionic acidemia: a neuropathology case report and review of prior cases.
        Arch Pathol Lab Med. 2003; 127: e325-e328
        • Peters S.G.
        • Pomare E.W.
        • Fisher C.A.
        Portal and peripheral blood short chain fatty acid concentrations after caecal lactulose instillation at surgery.
        Gut. 1992; 33: 1249-1252
        • Cummings J.H.
        • Pomare E.W.
        • Branch W.J.
        • Naylor C.P.
        • Macfarlane G.T.
        Short chain fatty acids in human large intestine, portal, hepatic and venous blood.
        Gut. 1987; 28: 1221-1227
        • Dankert J.
        • Zijlstra J.B.
        • Wolthers B.G.
        Volatile fatty acids in human peripheral and portal blood: quantitative determination vacuum distillation and gas chromatography.
        Clin Chim Acta. 1981; 110: 301-307
        • van de Poll M.C.
        • Siroen M.P.
        • van Leeuwen P.A.
        • Soeters P.B.
        • Melis G.C.
        • Boelens P.G.
        • et al.
        Interorgan amino acid exchange in humans: consequences for arginine and citrulline metabolism.
        Am J Clin Nutr. 2007; 85: 167-172
        • Siroen M.P.
        • van der Sijp J.R.
        • Teerlink T.
        • van Schaik C.
        • Nijveldt R.J.
        • van Leeuwen P.A.
        The human liver clears both asymmetric and symmetric dimethylarginine.
        Hepatology. 2005; 41: 559-565
        • van Eijk H.M.
        • Bloemen J.G.
        • Dejong C.H.
        Application of liquid chromatography-mass spectrometry to measure short chain fatty acids in blood.
        J Chromatogr B Analyt Technol Biomed Life Sci. 2009; 877: 719-724
        • Cummings J.H.
        • Macfarlane G.T.
        • Englyst H.N.
        Prebiotic digestion and fermentation.
        Am J Clin Nutr. 2001; 73: 415S-420S
        • Scheppach W.
        • Christl S.U.
        • Bartram H.P.
        • Richter F.
        • Kasper H.
        Effects of short-chain fatty acids on the inflamed colonic mucosa.
        Scand J Gastroenterol Suppl. 1997; 222: 53-57
        • Kiely E.M.
        • Ajayi N.A.
        • Wheeler R.A.
        • Malone M.
        Diversion procto-colitis: response to treatment with short-chain fatty acids.
        J Pediatr Surg. 2001; 36: 1514-1517
        • Kles K.A.
        • Chang E.B.
        Short-chain fatty acids impact on intestinal adaptation, inflammation, carcinoma, and failure.
        Gastroenterology. 2006; 130: S100-S105
        • Kleessen B.
        • Hartmann L.
        • Blaut M.
        Oligofructose and long-chain inulin: influence on the gut microbial ecology of rats associated with a human faecal flora.
        Br J Nutr. 2001; 86: 291-300
        • Fitch M.D.
        • Fleming S.E.
        Metabolism of short-chain fatty acids by rat colonic mucosa in vivo.
        Am J Physiol. 1999; 277: G31-G40
        • Hamer H.M.
        • Jonkers D.
        • Venema K.
        • Vanhoutvin S.
        • Troost F.J.
        • Brummer R.J.
        Review article: the role of butyrate on colonic function.
        Aliment Pharmacol Ther. 2008; 27: 104-119
        • Bergman E.N.
        • Wolff J.E.
        Metabolism of volatile fatty acids by liver and portal-drained viscera in sheep.
        Am J Physiol. 1971; 221: 586-592
        • Wong J.M.
        • de Souza R.
        • Kendall C.W.
        • Emam A.
        • Jenkins D.J.
        Colonic health: fermentation and short chain fatty acids.
        J Clin Gastroenterol. 2006; 40: 235-243
        • Alvaro E.
        • Andrieux C.
        • Rochet V.
        • Rigottier-Gois L.
        • Lepercq P.
        • Sutren M.
        • et al.
        Composition and metabolism of the intestinal microbiota in consumers and non-consumers of yogurt.
        Br J Nutr. 2007; 97: 126-133
        • Wolever T.M.
        • Josse R.G.
        • Leiter L.A.
        • Chiasson J.L.
        Time of day and glucose tolerance status affect serum short-chain fatty acid concentrations in humans.
        Metabolism. 1997; 46: 805-811
        • O'Keefe S.J.
        Nutrition and colonic health: the critical role of the microbiota.
        Curr Opin Gastroenterol. 2008; 24: 51-58