A ddcnbrooke's Hospital, C(ambridge SUMMARY Evidence for the occurrence of microbial breakdown of carbohydrate in the human colon has been sought by measuring short chain fatty acid (SCFA) concentrations in the contents of all regions of the large intestine and in portal, hepatic and peripheral venous blood obtained at autopsy of sudden death victims within four hours of death. Total SCFA concentration (mmol/kg) was low in the terminal ileum at 13±6 but high in all regions of the colon ranging from 131±9 in the caecum to 80± 11 in the descending colon. The presence of branched chain fatty acids was also noted. A significant trend from high to low concentrations was found on passing distally from caecum to descending colon. pH also changed with region from 5-6±0-2 in the caecum to 6-6±0 1 in the descending colon. pH and SCFA concentrations were inversely related. Total SCFA (~imol/l) in blood was, portal 375±70, hepatic 148±42 and peripheral 79±22. In all samples acetate was the principal anion but molar ratios of the three principal SCFA changed on going from colonic contents to portal blood to hepatic vein indicating greater uptake of butyrate by the colonic epithelium and propionate by the liver. These data indicate that substantial carbohydrate, and possibly protein, fermentation is occurring in the human large intestine, principally in the caecum and ascending colon and that the large bowel may have a greater role to play in digestion than has previously been ascribed to it.There is now much evidence' that dietary polysaccharides, both starch and non-starch polysaccharides (dietary fibre), escape digestion in the human small intestine

There is now substantial evidence that some dietary polysaccharides, notably dietary fiber, escape absorption in the small bowel and are then broken down in the large intestine of man. The main end products of this colonic digestive process, which is anerobic, are short chain fatty acids (SCFA), and acetic, propionic, and butyric acids. Although these acids are known to be absorbed from the colon, their subsequent fate and significance is unknown. We have measured venous blood SCFA levels in healthy subjects after a 16-h fast, and then following oral doses of either 50 mmol SCFA,5,10, or liter. Pectin fermentation was much slower, with blood acetate levels starting to rise after 6 h and remaining elevated at about twice fasting levels for the subsequent 18 h. However, areas under the blood acetate curves were closely related (r = 0.97; n = 5), whatever the source of acetate. These studies show that the large intestine makes an important contribution to blood acetate levels in man and that fermentation may influence metabolic processes well beyond the wall of this organ.

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The major end products of fermentation, short chain fatty acids (acetate, propionate, butyrate) were measured in portal and peripheral venous blood after the caecal instiliation of lactulose at surgery in patients undergoing elective cholecystectomy. Blood samples for short chain fatty acid measurement were taken before and at 15 minute intervals up to 60 minutes after caecal instillation of either 20 ml sterile saline or 6.7 g or 10 g lactulose. Fasting concentrations (n=28) The principal end products of fermentation are the short chain fatty acids acetate, propionate and butyrate and the gases carbon dioxide, methane and hydrogen.' In ruminants and other herbivores short chain fatty acids contribute substantially to basal energy requirements,2 while in man there have been few studies investigating the fate of these acids.3There are many lines of evidence now which suggest that fermentation occurs in the human colon and that absorption of the resultant short chain fatty acids is rapid and contributes significantly to portal and peripheral blood short chain fatty acid concentrations.' 3 The major short chain fatty acid, acetate, is also an important metabolic fuel and in species such as the rat, falling portal blood levels trigger active liver production of acetate.4 5Studies of the fermentation process in man and the fate of its short chain fatty acid end products have been limited by the inaccessibility of both the large bowel and the portal venous system. We have therefore attempted to establish in the present study not only that fermentation occurs in the human caecum but that short chain fatty acids are rapidly absorbed into the portal venous circulation and beyond by measuring short chain fatty acids in portal and peripheral blood after the caecal instillation of the fermentable carbohydrate lactulose in patients undergoing elective cholecystectomy. Methods PATIENTSTwenty eight patients (23 female, five male) in normal health, average age 47.6 (15.7) years (range 23-74) undergoing elective cholecystectomy for gall stones were randomly allocated to three groups. In two groups lactulose was injected into the caecum at surgery and in the third group sterile saline. Patients were maintained on polysaccharide free food for 24 hours before operation and none had taken antibiotics in the three months before surgery.

1. To test the hypothesis that the colon contributes significantly to venous plasma acetate concentrations, experiments were carried out in healthy volunteers and ileostomy patients. 2. Fasting plasma acetate levels were measured in 10 ileostomy patients and compared with those in 21 control subjects. Values in ileostomy patients (21.3 +/- 0.8 mumol/l) were significantly lower than in control subjects (48.0 +/- 4.2 mumol/l). 3. Plasma acetate concentration was estimated in eight healthy volunteers during 108 h of continuous fasting. Acetate concentrations rose significantly from 12 h (43.9 +/- 4.4 mumol/l) to 108 h of starvation (114.0 +/- 15.6 mumol/l) and fell back to normal fasting values on refeeding and another 12 h fast (44.3 +/- 4.7 mumol/l). 4. When colonic fermentation was stimulated after oral ingestion of 10 g of lactulose, the plasma acetate concentration increased significantly (from 44.0 +/- 7.4 to 114.4 +/- 16.2 mumol/l) in seven healthy control subjects. This rise was not affected by concomitant dosage of metronidazole. 5. These data suggest that there are at least two major sources of acetate in man, an endogenous source and the colon which probably becomes more important when fermentation of carbohydrate is occurring.