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Biomedical subjects

J H Cummings

Publications and source records attributed to J H Cummings.

At least 19 recordsLinked to original sources
PubMed1992

Fecal weight, colon cancer risk, and dietary intake of nonstarch polysaccharides (dietary fiber)

Low fecal weight and slow bowel transit time are thought to be associated with bowel cancer risk, but few published data defining bowel habits in different communities exist. Therefore, data on stool weight were collected from 20 populations in 12 countries to define this risk more accurately, and the relationship between stool weight and dietary intake of nonstarch polysaccharides (NSP) (dietary fiber) was quantified. In 220 healthy U.K. adults undertaking careful fecal collections, median daily stool weight was 106 g/day (men, 104 g/day; women, 99 g/day; P = 0.02) and whole-gut transit time was 60 hours (men, 55 hours; women, 72 hours; P = 0.05); 17% of women, but only 1% of men, passed < 50 g stool/day. Data from other populations of the world show average stool weight to vary from 72 to 470 g/day and to be inversely related to colon cancer risk (r = -0.78). Meta-analysis of 11 studies in which daily fecal weight was measured accurately in 26 groups of people (n = 206) on controlled diets of known NSP content shows a significant correlation between fiber intake and mean daily stool weight (r = 0.84). Stool weight in many Westernized populations is low (80-120 g/day), and this is associated with increased colon cancer risk. Fecal output is increased by dietary NSP. Diets characterized by high NSP intake (approximately 18 g/day) are associated with stool weights of 150 g/day and should reduce the risk of bowel cancer.

Adolescent↗
PubMed1992

Determination of dietary fibre as non-starch polysaccharides by gas-liquid chromatography.

An improved method is described for the measurement of total, soluble and insoluble dietary fibre as non-starch polysaccharides (NSP). An established procedure is modified to allow more rapid removal of starch and hydrolysis of NSP. In its present form the procedure is simpler and more robust than those previously published. In the modified method starch is removed enzymically within 50 min and NSP is precipitated with ethanol and then hydrolysed by treatment with sulfuric acid for 2 h. The constituent sugars can in turn be measured by gas-liquid chromatography, high-performance liquid chromatography or more rapidly by colorimetry. The improved procedure described here for the removal of starch and hydrolysis of NSP applies to all three techniques, but only the method for measurement of sugars by gas-liquid chromatography is described here in full.

Chromatography, Gas↗
PubMed1992

Novel detection by magnetic microcapsules in the human gastrointestinal tract of cross-linking agents and diet-dependent reactive oxygen species.

Semi-permeable magnetic microcapsules previously shown able to trap gastrointestinal carcinogens and containing polyethyleneimine (PEI) were covalently labelled with [14CH3], and administered for the first time to humans (six healthy volunteers, 1.3 microCi/dose) in gelatin capsules together with radio-opaque gut transit markers (ROM), in order both to seek human endogenous cross-linking or bifunctional alkylating agents and assess gut transit features. No ill-effects were reported. Faecal ROM and 14C excretions were well correlated (r = 0.96), and net 14C recovery in faeces was 83-96%. Microcapsules were separated magnetically from faeces and 29-81% of specific labelling of microcapsules (nCi/10(6)) was found to have been removed during GI transit. Label cleavage out of these microcapsules was also found following in vitro anaerobic incubation with faecal slurries from two volunteers. On treatment with H2O2, label was removed selectively from the Fe-containing core in a dose-dependent manner. Therefore, label cleavage in vivo (not observed in rats consuming chow but found notably on consumption of low-fibre and/or high-beef human diets) is likely to arise from low mol. wt substances that give Fenton reaction producing hydroxyl radicals and oxidative demethylation. After GI transit, extensive core to membrane cross-linking in the microcapsules was found and was inversely related to faecal output. Cross-linking also was obtained to a greater extent during in vitro anaerobic incubation with faecal slurries. The GI mucosa would also be exposed to both types of agents, and several features of this microcapsule monitoring are in accord with putative risk-modulating effects. This first use of microcapsules for biomonitoring of the human GI tract thus seemed to be without hazard, and revealed extensive levels of agents likely to cause DNA damage.

Animals↗
PubMed1992

Comparison of fermentation reactions in different regions of the human colon.

Colonic contents were obtained from two human sudden-death victims within 3 h of death. One of the subjects (1) was methanogenic, the other (2) was a non-CH4 producer. Measurements of bacterial fermentation products showed that in both individuals short-chain fatty acids, lactate and ethanol concentrations were highest in the caecum and ascending colon. In contrast, products of protein fermentation, such as ammonia, branched chain fatty acids and phenolic compounds, progressively increased from the right to the left colon, as did the pH of gut contents. In Subject 1, cell population densities of methanogenic bacteria (MB) increased distally through the gut and methanogenic activity was lower in the right (0.78-1.18 mumol CH4 produced/h/g dry wt contents) than in the left colon (1.34 mumol CH4 produced/h/g dry wt contents). Methane production rates did not correlate with MB numbers. Sulphate-reducing bacteria (SRB) were not found and dissimilatory sulphate reduction was not detected in any region of the colon. Methanogenic bacteria did not occur in subject 2, but high numbers of SRB were present throughout the gut (ca 10(9)/g dry wt contents). Sulphate reduction rates were maximal in the ascending and transverse colons (0.24 and 0.22 mumol 35SO4(2-) reduced/h/g dry wt contents, respectively). Short-chain fatty acid production by caecal contents was up to eight-fold higher than contents from the sigmoid/rectum. These findings demonstrate significant differences in fermentation reactions in different regions of the large gut.

Adult↗
PubMed1992

Role of dietary sulphate in the regulation of methanogenesis in the human large intestine.

Hydrogen produced during colonic fermentation may be excreted, or removed by H2 consuming bacteria such as methanogenic and sulphate reducing bacteria. In vitro, sulphate reducing bacteria compete with methanogenic bacteria for hydrogen when sulphate is present. In this study the hypothesis that sulphate in the diet could alter CH4 production in vivo has been tested. Six methane excreting volunteers were fed a low sulphate diet (1.6 mmol/d) for 34 days with the addition of 15 mmol sodium sulphate from days 11-20. Breath methane was measured and viable counts and metabolic activities of methanogenic bacteria and sulphate reducing bacteria determined in faeces. Whole gut transit time and daily stool weight were also measured. When sulphate was added to the diet, breath methane excretion decreased in three of the subjects while faecal sulphate reduction rates rose from 7.5 (0.5) to 20.3 (4.3) nmol SO4 reduced/h/g faeces. Sulphate reducing bacteria, which were not detected during the control diet, were found and viable counts of methanogenic bacteria fell from 10(7)-10(9)/g faeces to 10(6)/g. Methanogenic counts and breath CH4 recovered after sulphate addition was stopped. No change was found in the other three subjects. Faecal weights and transit times were not different between study periods. It is concluded that methanogenesis is regulated by dietary sulphate if sulphate reducing bacteria are present. Dietary sulphate may allow growth of sulphate reducing bacteria which inhibit the growth of methanogenic bacteria. This may explain the absence of CH4 in the breath of many people in western populations.

Adult↗
PubMed1992

Classification and measurement of nutritionally important starch fractions.

For nutritional purposes, starch in foods may be classified into rapidly digestible starch (RDS), slowly digestible starch (SDS) and resistant starch (RS). RS may be further divided into three categories according to the reason for resistance to digestion. A method is reported for the measurement of total starch, RDS, SDS, RS and three RS fractions in starchy foods, using controlled enzymic hydrolysis with pancreatin and amyloglucosidase. The released glucose is measured by colorimetry, using a glucose oxidase kit. Values for RDS and SDS in foods obtained by the method reflect the rate of starch digestion in vivo. Values for RS are similar to the amounts of starch escaping digestion in the small intestine of ileostomates, and are a guide to the amounts of starch likely to enter the colon for fermentation. Results are given for a number of starchy foods.

Dietary Fiber↗
PubMed1992

Production, metabolism, and excretion of hydrogen in the large intestine.

Hydrogen is produced during fermentation in the large intestine and may be excreted in breath and flatus or further metabolized by the flora. However, there is little information about total H2 excretion from different substrates or the extent to which it is metabolized in the colon. We have therefore measured total H2 and methane excretion in 10 healthy subjects using a whole body calorimeter. Breath gases were measured simultaneously with total excretion in response to lactulose, pectin, and banana starch. Metabolic activities of the predominant H2 consuming anaerobes (methanogenic, sulfate reducing, and acetogenic bacteria) were measured in fecal samples. Total H2 excretion on a starch and fiber-free diet was 35 +/- 6.1 mL/24 h +/- SEM. H2 from 7.5 g, 15 g, and 22.5 g lactulose was 88.1 +/- 22.4 mL, 227.0 +/- 60.7 mL, and 321.8 +/- 79.2 mL. Four of the subjects also excreted CH4, which was 51.3 +/- 5.5 mL, 97.3 +/- 18.4 mL, and 157.5 +/- 36.3 mL for the respective lactulose doses. H2 excretion was less in methanogenic subjects (7.9 mL/g lactulose) than in nonmethanogenic (17.3 mL/g), but total H2 excreted as, hydrogen + methane, was 34.9 mL/g. H2 from pectin (20 g) was 14.1% +/- 3.2% and from starch (22.2 g) 38.6% +/- 9.2% of an equivalent lactulose dose. Sixty-five percent of total H2 and CH4 was expired in breath at total excretion rates up to 200 mL/24 h. Over this the proportion decreased to 25% with an overall average of 58%. Only subjects with CH4 excretion in vivo showed methanogenesis in feces, whereas nonmethanogenic subjects showed high sulfate-reducing activity in feces (58.7 +/- 5.6 nmol 35SO4 reduced.h-1.g-1 wet wt vs. 7.9 +/- 2.0 nmol.h-1.g-1 in methanogens). Acetogenesis rates were very low in both groups. It was concluded that H2 excretion varies with different substrates. The proportion of H2 that is exhaled in breath is higher than currently accepted and varies with total excretion rate. Substantial amounts of H2 are consumed by methanogenic and sulfate-reducing bacteria.

Adolescent↗
PubMed1992

para-amino benzoic acid in the assessment of completeness of 24-hour urine collections from hospital outpatients and the effect of impaired renal function.

Eighteen (29%) of 24-h urine collections made by 63 hospital outpatients attending a gastroenterology clinic were incomplete, as judged by 24 h urine recovery of an oral marker, para-amino benzoic acid (PABA), despite more than the usual efforts to obtain complete collections. Incomplete collections contained significantly less sodium, urea and total nitrogen than full collections. Average outputs were 134 mmol and 103 mmol per day for sodium (P less than 0.02); 301 mmol and 223 mmol for urea (P less than 0.001); and 10.1 g and 8.3 g nitrogen (P less than 0.01) in the complete and incomplete collections respectively. In renal outpatients with a plasma creatinine in excess of 125 mumol per litre, urine recoveries of PABA were reduced, but within the expected range in renal patients whose plasma creatinine was normal.

4-Aminobenzoic Acid↗
PubMed1991

The contribution of the large intestine to blood acetate in man.

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.

Acetates↗
PubMed1991

Metabolism of dietary sulphate: absorption and excretion in humans.

Dietary sulphate may affect colonic pathophysiology because sulphate availability determines in part the activity of sulphate reducing bacteria in the bowel. The main product of sulphate reducing bacterial oxidative metabolism, hydrogen sulphide, is potentially toxic. Although it is generally believed that the sulphate ion is poorly absorbed, there are no available data on how much sulphate reaches the colon nor on the relative contributions from diet and endogenous sources. To resolve these questions, balance studies were performed on six healthy ileostomists and three normal subjects chosen because they did not have detectable sulphate reducing bacteria in their faeces. The subjects were fed diets which varied in sulphate content from 1.6-16.6 mmol/day. Sulphate was measured in diets, faeces (ileal effluent in ileostomists), and urine by anion exchange chromatography with conductivity detection. Overall there was net absorption of dietary sulphate, with the absorptive capacity of the gastrointestinal tract plateauing at 5 mmol/day in the ileostomists and exceeding 16 mmol/day in the normal subjects. Endogenous secretion of sulphate in the upper gastrointestinal tract was from 0.96-2.6 mmol/day. The dietary contribution to the colonic sulphate pool ranged up to 9 mmol/day, there being linear identity between diet and upper gastrointestinal losses for intakes above 7 mmol/day. Faecal losses of sulphate were trivial (less than 0.5 mmol/day) in the normal subjects at all doses. It is concluded that diet and intestinal absorption are the principal factors affecting the amounts of sulphate reaching the colon. Endogenous secretion of sulphate by colonic mucosa may also be important in determining amounts of sulphate in the colon.

Aged↗
PubMed1991

Measurement of starch fermentation in the human large intestine.

Starch, not fibre, is probably the major substrate for fermentation in the human colon. However, quantitating the amount of starch that resists pancreatic amylase and thus escapes digestion in the small bowel is difficult. A number of techniques have been employed in man and are reviewed here, including direct intubation of the ileum, the ileostomy model, and breath studies. The results of a series of studies of the digestion of starch from potato and banana are reported. When fed to ileostomy patients, 3% of hot potato starch and 12% of cold potato starch were resistant to digestion, as was 75% of banana starch. In feeding experiments with healthy volunteers none of the starch was recoverable in faces, indicating its complete fermentation in the colon. Breath H2 measurements after test meals of these starches indicated that only 2-5% of potato starch and 7-12% of banana starch was fermented. A single blood acetate measurement timed to coincide with peak breath H2 was not useful. However, a number of problems with breath H2 studies are discussed, and it is suggested that either ileal intubation or the ileostomy model are the most reliable techniques presently available, with serial blood acetate determinations also potentially valuable. Overall on Western diets, approximately 10% of all starch is probably resistant starch.

Acetates↗
PubMed1990

The effect of dietary nitrate on nitrate and nitrite excretion in man.

Dietary nitrate and nitrite may affect colonic pathophysiology. These anions influence fermentation, and nitrite has been shown to augment sodium absorption by the colon and participate in the formation of N-nitroso compounds. There is, however, no general agreement as to how much dietary nitrate and nitrite reaches the colon. To help resolve this question, balance studies were performed on six healthy ileostomy subjects who were given diets that varied in nitrate content from 0.83 to 5.20 mmol/d. Nitrate and nitrite excretion in ileal effluent and urine were measured by anion-exchange chromatography with conductivity detection. There was no significant nitrite in the diets, urine or ileal effluent. Dietary nitrate was largely excreted in urine (1.31-4.25 mmol/d). The urinary excretion findings indicated net synthesis of nitrate at low dietary intakes and net catabolism of nitrate at high intakes. Nitrate losses in ileal effluent were very low (0.03-0.05 mmol/d, 0.03-0.06 mmol/kg) and unrelated to intake for all the diets. It is concluded that dietary nitrate and nitrite do not enter the colon from the small intestine in amounts that would affect fermentation and mucosal metabolism in man. The possibility of significant amounts of nitrate reaching the colon via blood in normal subjects has not been excluded.

Aged↗
PubMed1990

Non-invasive method for delivery of tracer substances or small quantities of other materials to the colon.

A miniature osmotic pump has been developed (Osmet) with ALZA, Palo Alto, USA, which can be swallowed, will pass through the stomach and small intestine and then deliver its contents (240 microliters) over eight hours in the large bowel. In vitro studies showed the pumps started to discharge after four to five hours and emptied at a reasonably constant rate of 20.4 microliters/h from 9-16 h (9.6%/h). In vivo studies using gamma-scintigraphy in seven healthy subjects show that the pumps left the fasting stomach at 1.2 h (range 0-3) and arrived in the caecum by 6.4 h (range 5-9). Mean start-up time was 5.3 (0.2) h and the rate of discharge was 15.9 microliters/h for pumps studied from 6-12 h and 17.2 microliters/h for those studied from 10-20 h. This device is simple, safe and effective for the delivery of tracer substances to the caecum and colon without interfering with patients' normal lifestyle.

Adult↗
PubMed1990

Alternative pathways for hydrogen disposal during fermentation in the human colon.

Hydrogen gas, which is produced during fermentation in the human colon, is either excreted in breath or metabolised by gut bacteria through a variety of pathways. These may include methanogenesis, dissimilatory sulphate reduction, and acetogenesis. To determine which of these routes predominates in the large intestine, stools were taken from 30 healthy subjects and incubated as 5% (w/v) slurries with Lintner's starch. In 23 of 30 subjects, methane production was the main method of hydrogen disposal. In the remaining seven, high rates of sulphate reduction were recorded together with raised production of H2S. All samples showed relatively low rates of hydrogen evolution and of acetate formation from CO2 and H2. Sulphate reduction and methanogenesis seem to be mutually exclusive in the colon and this is probably linked to sulphate availability. Sulphate reduction, methanogenesis, and acetogenesis were strongly influenced by pH. Sulphate reduction was optimal at alkaline pH values whereas methane production was maximal at a neutral pH and acetogenesis favoured acidic conditions. Faecal H2S values were related to carriage of sulphate reducing bacteria. These data show that a number of competing pathways for hydrogen disposal are possible in the large gut and that a variety of factors such as colonic pH and sulphate availability can determine which of these mechanisms predominates.

Acetates↗
PubMed1990

Effects of dietary propionate on carbohydrate and lipid metabolism in healthy volunteers.

Propionate produced in the colon from the fermentation of alpha-amylase-resistant starch and non-starch polysaccharides, is cholesterol lowering and gluconeogenic in animal models. In humans, little is known about the effect of propionate on metabolism. In a double-blind, paired-comparison, placebo-controlled study, the diet of 10 healthy female volunteers, aged 20-22 yr, was supplemented for a period of 7 wk with 7.5 g sodium propionate daily in capsule form, while the diet of the 10 control group members was supplemented with dibasic calcium phosphate in identical capsules as placebo. Propionate supplementation did not lower total serum cholesterol (TC), but increased HDLC (9.5%) (p less than 0.05) and triglyceride levels (16.7%, p less than 0.02) and decreased fasting serum glucose and maximum insulin increments during glucose tolerance tests (p less than 0.05). The results suggest that the improvement in glucose tolerance and insulin sensitivity and the known beneficial effect of dietary fiber on HDL metabolism may in part be mediated through effects of propionate on hepatic carbohydrate metabolism.

Adult↗