Original ArticleShort chain fatty acids exchange: Is the cirrhotic, dysfunctional liver still able to clear them?
Introduction
Prebiotics, such as plant cell wall material, constitute an important source for substrates that alter gut microbiota and microbial metabolism. Humans lack enzymes to break down undigestible carbohydrates and therefore prebiotics pass the upper gastro-intestinal tract relatively unaffected.1, 2 Colonic bacteria ferment these products to short chain fatty acids (SCFA, notably acetate, propionate and butyrate).3, 4 Supplementing diets with prebiotics (e.g. yoghurts) to improve intestinal health has become increasingly popular since these products are commercially available without a prescription. Although several beneficial effects of prebiotics are proven, the exact mechanisms of action remain largely unknown.5, 6
Following their production, SCFA are absorbed by colonic epithelium and are metabolized at three major sites: the colonic epithelium, the liver and peripheral muscle tissue.7 SCFA are oxidized and used as an energy source by colonic epithelial cells, with butyrate as preferred substrate. Acetate, propionate and the remainder of butyrate are transported to the liver. Here, propionate serves as a substrate for gluconeogenesis and may inhibit cholesterol synthesis, whereas acetate is utilized as a substrate for the synthesis of long chain fatty acids, glutamine, glutamate and betahydroxybutyrate.8 Butyrate is oxidized directly by the hepatocytes preventing high, toxic systemic concentrations.9, 10
Our group recently showed that the liver of patients undergoing major upper abdominal surgery and having normal liver function, is capable of scavenging all SCFA released by the gut.11 The aim of the present study was to investigate to which extent patients with cirrhosis of the liver are still able to metabolize portal derived short chain fatty acids by the liver.
Section snippets
Patients
The study was performed in the Royal Infirmary of Edinburgh (UK). Metabolically stable patients with biopsy proven cirrhosis of the liver, who had previously received a transjugular intrahepatic portosystemic shunt (TIPSS) for the treatment of complications of liver cirrhosis and who subsequently underwent routine portography to check TIPSS patency were studied (Table 1). Exclusion criteria were severe ascites, pitting peripheral oedema, hepatic encephalopathy, recent upper gastro-intestinal
General
Twelve patients were included in the study. All patients had patent TIPSS, placed on average 25.0 ( ± 3.5) months before, for treatment of variceal bleeding (Table 1). During the experiment, there were no unwanted side effects. The mean plasma flows of the group were: portal flow 723 ( ± 100) ml/min and liver flow 609 ( ± 95) ml/min. These flows are comparable with literature data.15, 16, 17
Gut SCFA exchange
To calculate the production of SCFA by the gut, the arterial and portal venous concentrations were measured.
Discussion
The results of the present study show that in patients with stable liver cirrhosis the gut produced significant amounts of acetate, propionate and butyrate after an overnight fast. The liver of patients with stable cirrhosis was able to take up butyrate and propionate, which prevented a rise in their respective systemic concentrations. Acetate was not taken up by the liver, causing a net release from the splanchnic area. Furthermore, hepatic uptake of butyrate was strongly correlated with its
Conclusion
The present data show that the liver of patients with stable cirrhosis is able to take up butyrate and propionate, similar to the situation in healthy individuals. Furthermore, hepatic uptake of butyrate is correlated with arterial butyrate concentration. This indicates a large capacity of the liver to take up butyrate, also evidenced by a low hepatic venous concentration. These findings add valuable information to the existing knowledge about the physiology of SCFA handling in humans and might
Conflict of interest
The authors have no conflict of interest.
Acknowledgements
JG Bloemen analyzed the data and wrote the manuscript, SWM Olde Damink participated in the study design, participated in data collection and advised on data interpretation and critically reviewed the manuscript, K Venema critically reviewed the manuscript, WA Buurman advised on data interpretation and critically reviewed the manuscript, R Jalan participated in the study design, data collection and drafting the manuscript, CHC Dejong participated in the study design, advised on data
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