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Biomedical subjects

J H Cummings

Publications and source records attributed to J H Cummings.

At least 37 records · Page 2Linked to original sources

Rapidly available glucose in foods: an in vitro measurement that reflects the glycemic response.

BACKGROUND: A chemically based classification of dietary carbohydrates that takes into account the likely site, rate, and extent of digestion is presented. The classification divides dietary carbohydrates into sugars, starch fractions, and nonstarch polysaccharides, and groups them into rapidly available glucose (RAG) and slowly available glucose (SAG) as to the amounts of glucose (from sugar and starch, including maltodextrins) likely to be available for rapid and slow absorption, respectively, in the human small intestine. OBJECTIVE: We hypothesize that RAG is an important food-related determinant of the glycemic response. DESIGN: The measurement of RAG, SAG, and starch fractions by an in vitro technique is described, based on the measurement by HPLC of the glucose released from a test food during timed incubation with digestive enzymes under standardized conditions. Eight healthy adult subjects consumed 8 separate test meals ranging in RAG content from 11 to 49 g. RESULTS: The correlation between glycemic response and RAG was highly significant (P < 0.0001) and a given percentage increase in RAG was associated with the same percentage increase in glycemic response. After subject variation was accounted for, RAG explained 70% of the remaining variance in glycemic response. CONCLUSIONS: We show the significance of in vitro measurements of RAG in relation to glycemic response in human studies. The simple in vitro measurement of RAG and SAG is of physiologic relevance and could serve as a tool for investigating the importance of the amount, type, and form of dietary carbohydrates for health.

Adult↗

Sulfur metabolism in ulcerative colitis: investigation of detoxification enzymes in peripheral blood.

Two enzymes of detoxification were studied in blood samples from 27 patients with ulcerative colitis (UC) and 18 controls to determine whether there is an abnormality in sulfur metabolism in UC. Thiol methyltransferase (TMT) activity was measured in erythrocyte membranes as the extent of conversion of 2-mercaptoethanol to S-methyl-2-mercaptoethanol with [3H]methyl-S-adenosyl methionine as methyl donor. Phenol sulfotransferase (PST) activity was measured in platelet homogenates as the extent of sulfation of p-nitrophenol with 3-phosphoadenosine 5-phospho[35S]sulfate (PAPS) as sulfate donor. TMT activity was significantly higher in UC patients (27.0 vs 17.1 nmol/mg protein/hr; P < 0.005). No difference in PST activity was found. We conclude that TMT may be up-regulated in UC to detoxify excess hydrogen sulfide exposed to the peripheral blood compartment. This may arise from either increased luminal sulfide production or reduced colonic detoxification.

Adult↗

Growth of a human intestinal Desulfovibrio desulfuricans in continuous cultures containing defined populations of saccharolytic and amino acid fermenting bacteria.

Ecological and physiological effects of the sulphate-reducing bacterium (SRB) Desulfovibrio desulfuricans on other intestinal organisms were investigated in anaerobic chemostats (dilution rate approximately 0.2 h-1). Reproducible defined bacterial communities were used in these experiments, comprising 14 different saccharolytic and amino acid fermenting species: Bifidobacterium longum, Bif. adolescentis, Bif. pseudolongum, Bif. infantis, Bacteroides thetaiotaomicron, Bact. vulgatus, Lactobacillus acidophilus, Enterococcus faecalis, Ent. faecium, Escherichia coli, Clostridium perfringens, Cl. butyricum, Cl. innocuum, Cl. bifermentans. Lactobacillus and Cl. bifermentans populations never rose above minimum detection limits (log10 2.0 and 4.0, respectively) under the experimental conditions employed in these studies. Inclusion of Des. desulfuricans in bacterial cultures (c. log10 8.4 viable cells ml-1) resulted in marked reductions (i.e. greater than 1 log) in planktonic cell population densities of several species, particularly Bif. longum, Cl. perfringens and Bif. pseudolongum. The two bacteroides species were unaffected by Des. desulfuricans, while numbers of Cl. butyricum increased. Extensive wall growth developed in the SRB culture, consisting mainly of Des. desulfuricans (log10 9.2 viable cells ml-1), Bact. thetaiotaomicron and Bact. vulgatus, with lesser numbers of facultative anaerobes, Cl. perfringens and Bif. longum. Wall growth was associated with a reduction in planktonic cell mass and increased acid production by the cultures. Chemotaxonomic study of chemostat microbiotas, on the basis of cellular fatty acid methyl ester (FAME) analyses, showed the existence of characteristic bacteroides (C15) and bifidobacterial (C18) markers, but desulfovibrio markers (i-C15:0, C16:0, i-C17:1) could be identified. The metabolic activities of saccharolytic organisms were altered in the SRB chemostat, including synthesis of a number of hydrolytic enzymes involved in carbohydrate breakdown, such as alpha-galactosidase, alpha-glucosidase and beta-galactosidase, together with several mucinolytic enzymes. High concentrations of sulphide (8.2 mmol 1-1) were detected in the SRB chemostat, suggesting that this metabolite may have been inhibitory to some species. Saccharolytic organisms growing in the SRB fermenter utilized more starch, but less galactose-containing polymers, which correlated with the observed glycosidase activities. Profound differences were also recorded with respect to fermentation product formation in the chemostats, where a major switch to acetate production occurred in the SRB culture, with concomitant reductions in propionate, butyrate and lactate, which is an important electron donor for desulfovibrios.

Amino Acids↗

Apolipoprotein E genotype modulates the effect of black tea drinking on blood lipids and blood coagulation factors: a pilot study.

Apolipoprotein E (ApoE) genotype was determined in sixty-five subjects who had taken part in a 4-week randomized crossover trial to compare the effect of six mugs of black tea per day v. placebo on blood lipids and blood coagulation factors. Four ApoE genotype variants (seven E2/E3, forty-five E3/E3, twelve E3/E4 and one E4/E4) were found. ApoE allele frequency was within the range typical for Caucasian populations (ApoE-E2 5.4%; ApoE-E3 83.8%; ApoE-E4 10.8%). Individuals bearing at least one E4 allele had substantially higher levels of serum total cholesterol, LDL cholesterol and triacylglycerols. Mean plasminogen activator inhibitor (PAI-1) activity was higher in ApoE-E4 allele-bearing individuals (E3/E4 + E4/E4, 11.89 (SE 1.27) U/ml; E3/E3, 9.19 (SE 0.80) U/ml; E2/E3, 7.21 (SE 1.04) U/ml, P values of E4-group v. E3 and E2 being respectively 0.093 and 0.030). These unexpected findings imply that elevated PAI-1 activity may be a hitherto unrecognized additional factor involved in the increased cardiovascular disease risk associated with apoE-E4 allele. The interactions between tea drinking and genotype were also examined. In the E3/E3 homozygotes, HDL-cholesterol was significantly reduced in the tea period (mean placebo 1.54 mmol/l v. mean tea 1.50 mmol/l, P = 0.027). In the E2/E3 group, triacylglycerol concentration was significantly reduced (mean placebo 1.18 mmol/l v. mean tea 1.09 mmol/l, P = 0.039). Tea also caused a significant decrease of PAI-1 activity in the subjects with E2/E3 genotype (mean placebo 7.21 U/ml v. mean tea 5.88 U/ml, P = 0.007). In the other two genotype groups, there was no significant effect of tea. The results indicate that tea drinking has a beneficial effect on some cardiovascular disease risk-associated factors, especially in E2 allele-bearing individuals. Dietary intervention may be particularly effective in population groups with certain genetic characteristics.

Adult↗

Functional food science and gastrointestinal physiology and function.

The gut is an obvious target for the development of functional foods, acting as it does as the interface between diet and the metabolic events which sustain life. The key processes in digestive physiology which can be regulated by modifying diet are satiety, the rate and extent of macronutrient breakdown and absorption from the small bowel, sterol metabolism, the colonic microflora, fermentation, mucosal function and bowel habit, and the gut immune system. The intestinal microflora is the main focus of many current functional foods. Probiotics are foods which contain live bacteria which are beneficial to health whilst prebiotics, such as certain non-digestible oligosaccharides which selectively stimulate the growth of bifidobacteria in the colon, are already on the market. Their claimed benefits are to alleviate lactose maldigestion, increase resistance to invasion by pathogenic species of bacteria in the gut, stimulate the immune system and possibly protect against cancer. There are very few reports of well-designed human intervention studies with prebiotics as yet. Certain probiotic species have been shown to shorten the duration of rotavirus diarrhoea in children but much more work is needed on the mechanism of immunomodulation and of competitive exclusion and microflora modification. The development of functional foods for the gut is in its infancy and will be successful only if more fundamental research is done on digestive physiology, the gut microflora, immune system and mucosal function.

Bacteria↗

Dietary carbohydrates and the colonic microflora.

The world of the colonic microflora has lain dormant in recent years, but is coming alive now with the advent of new chemical and molecular technologies for identifying bacteria, and the emergence of the concepts of biofilms, pro- and prebiotics. That bacteria play an essential role in barrier resistance to infection, ulcerative colitis and colorectal cancer is slowly becoming clear. New potential therapeutic avenues using bacteria should soon start to open up. Scientifically we lack an understanding of the mechanisms at work.

Animals↗

Quantitation of DNA from exfoliated colonocytes isolated from human stool surface as a novel noninvasive screening test for colorectal cancer.

The only widely used screening test for early detection of colorectal cancer, the fecal occult blood test, lacks both sensitivity and specificity because it relies upon incidental bleeding rather than the neoplastic process. With the purpose of developing a new noninvasive diagnostic approach, we quantified DNA extracted from cells isolated from the surface of human stools by a novel procedure. Stools collected from 28 healthy individuals, 17 colorectal cancer patients, and 11 colorectal polyp patients were analyzed. A stool DNA index (SDNAI), expressed as DNA amount in nanograms per gram of stool, had a remarkable 4.5-fold difference in mean values between colorectal cancer patients and healthy people of comparable age. SDNAI was 2133 +/- 407 in the cancer group versus 469 +/- 65 in healthy people of the older (> 50 years) age group (P = 0.0005). The difference was independent of tumor location and size. If 700 ng of DNA/g of stool was taken as a cutoff SDNAI value in discrimination between older healthy people and cancer patients, sensitivity and specificity values reached 1.00 and 0.81, respectively. Age dependence of SDNAI was demonstrated by substantially lower SDNAI values (mean, 227 +/- 41) in younger healthy individuals. Polyp patients sometimes displayed elevated SDNAI values, but considerable variation was observed (mean, 1215 +/- 548). These preliminary findings indicate that SDNAI provides a novel, simple, and powerful noninvasive test for colorectal cancer early detection and screening. The fundamental advantage of the SDNAI is that it directly characterizes colonic epithelium involved in carcinogenesis.

Adult↗

Nutritional aspects of dissimilatory sulfate reduction in the human large intestine.

In contrast to other anaerobic ecosystems, such as marine and estuarine sediments, there is a lack of information on the nutritional requirements of human gut sulfate-reducing bacteria (SRB). Various substrates stimulated sulfate reduction in mixed culture, including short-chain fatty acids and other organic acids, alcohols, and amino acids (but not sugars or aromatic compounds). However, the use of sodium molybdate as a specific inhibitor of sulfate reduction caused an accumulation of ethanol and malonate only, and reduced the rate of utilization of lactate. This indicates the importance of these electron donors for sulfate reduction. Since ethanol and lactate are primarily utilized by members of the Desulfovibrio genus, the results suggest a physiologically important role for this group. Experiments with two strains of Desulfovibrio desulfuricans isolated from human feces demonstrated that both were able to reduce sulfite, thiosulfate or nitrate in the absence of sulfate. In addition, one strain (DsvUC1) was able to grow by fermentative metabolism, although the second strain (DsvFD1) showed more restricted fermentative growth. The data indicate that desulfovibrios are ecologically the most significant group of SRB in the human colon, and that colonic isolates belonging to this genus are versatile, in terms of both the electron acceptors and donors that they are able to utilize.

Acetates↗

A new look at dietary carbohydrate: chemistry, physiology and health. Paris Carbohydrate Group.

The current view of dietary carbohydrates as simply providing us with energy is outdated. Because of their varied chemistry and physical form the rate and extent to which the different types are digested in and absorbed from the small intestine varies. This in turn leads to affects on satiety, blood glucose and insulin, protein glycosylation, lipids and bile acids. Some carbohydrates reach the colon where they are fermented and affect many aspects of large bowel function, colonocyte and hepatic metabolism. A new framework for classifying and measuring food carbohydrates is needed to allow a greater understanding of the role of individual species in health and to inform the public of their importance. A classification based primarily on molecular size (degree of polymerisation) into sugars, oligosaccharides and polysaccharides, is suggested, with sub-groups identified by the nature of the monosaccharides. Greater knowledge of the chemical and physical properties of carbohydrates allow a more precise relation with physiology and health to be drawn. The Carbohydrate Group met in Paris in December 1995 at the invitation of Gerard Pascal, Director of CNERNA. Financial support for the meeting was provided by CNERNA.

Carbohydrates↗

Diet and haemostasis: time for nutrition science to get more involved.

Abnormal haemostasis, and specifically a pre-thrombotic state characterized by hypercoagulability, increased platelet aggregation and impaired fibrinolysis, is associated with increased atheroma and thrombosis. The recent literature clearly indicates that diet may prevent or be used to treat some abnormal haemostatic states. There are reports on effects of energy intake and expenditure, alcohol consumption, intakes of total fat, different fatty acids, fish oil, NSP and vitamins on markers of coagulation, platelet function and fibrinolysis. Some of the confusion and controversy in this field has arisen because the wrong markers of haemostasis have been measured in dietary trials. Moreover, many of the studies have lacked good dietary control. It is suggested that more sensitive, functional markers of the balance between the different facets of the haemostatic system should be measured. It is also important to test hypotheses developed from known observations and to propose mechanisms of action of the various dietary factors, based on our improved understanding of the haemostatic system.

Alcohol Drinking↗

Effect of black tea drinking on blood lipids, blood pressure and aspects of bowel habit.

Thirty-one men (47 (SD 14) years) and thirty-four women (35 (SD 13) years) took part in a 4-week randomized cross-over trial to compare the effect of six mugs of black tea daily v. placebo (water, caffeine, milk and sugar) on blood lipids, bowel habit and blood pressure, measured during a run-in period and at the end of weeks 2, 3 and 4 of the test periods. Compliance was established by adding a known amount of p-aminobenzoic acid (PABA) to selected tea bags, and then measuring its excretion in urine. Mean serum cholesterol values during run-in, placebo and on tea drinking were 5.67 (SD 1.05), 5.76 (SD 1.11) and 5.69 (SD 1.09) mmol/l (P = 0.16). There were also no significant changes in diet, LDL-cholesterol, HDL-cholesterol, triacylglycerols, and blood pressure in the tea intervention period compared with placebo. Compared with placebo, stool consistency was softened with tea (P = 0.04), and no other differences were found in bowel habit. Results were unchanged when fifteen 'non-compliers', whose PABA excretion indicated that fewer than six tea bags had been used, were excluded from the analysis, and when differences between run-in and tea periods were considered separately for those who were given tea first or second.

4-Aminobenzoic Acid↗

Effect of meat and resistant starch on fecal excretion of apparent N-nitroso compounds and ammonia from the human large bowel.

N-nitroso compounds are produced in the human large intestine, but little is known about the dietary modulation of their synthesis at this site. The effects of meat and resistant starch on the fecal excretion of N-nitroso compounds, measured as apparent total N-nitroso compounds (ATNC), were therefore investigated in a crossover study involving eight healthy men. Three controlled diets that differed in the amount of meat (40 or 600 g) and resistant starch (37 g added to 600 g meat diet) were fed in random order, and fecal ATNC, as well as fecal ammonia and parameters of bowel function, were measured after 19 days of dietary adaptation. Mean ATNC excretion during the high-meat period was 114 micrograms/day, three times that during the low-meat period of 35 micrograms/day (p = 0.02); ammonia excretion was twice that during the low-meat period: 2.9 vs. 1.4 mmol/day (p = 0.03). The fecal ATNC were dissolved in the fecal water, and 45% had a molecular weight < 3,000. The addition of readily fermentable resistant starch to the high-meat diet significantly increased stool output from 118 to 153 g/day and decreased fecal pH from 7.2 to 6.6 but had no significant effect on fecal ATNC (151 micrograms/day), ammonia (3.7 mmol/day), whole gut transit time, urinary nitrate, or plasma urea. ATNC produced in the large bowel in association with a high-meat intake could represent an important source of DNA-damaging alkylating agents in the human large bowel.

Adult↗

Digestion and physiological properties of resistant starch in the human large bowel.

The digestion of four sources of resistant starch (RS) has been studied in twelve healthy volunteers who ate controlled diets for 15 d periods. RS from potato, banana, wheat and maize (17-30 g/d) was compared with a starch-free diet, a diet containing wheat starch that was fully digested in the small intestine, and with 18.4 g NSP from brand/d. RS increased stool wet weight by 1.6 g/d per g RS fed for potato, 1.7 for banana, 2.5 for wheat and 2.7 for maize, but this was significantly less than bran NSP at 4.9 g/g. RS was extensively digested in twenty-seven of thirty-four diet periods but five subjects were unable to break down one or two of the RS sources. Faecal N and energy excretion were increased. RS decreased NSP breakdown and RS2 (resistant starch granules) tended to prolong transit time. All forms of RS increased faecal total short-chain fatty acid excretion. RS2 (from potato and banana) gave greater proportions of acetate in faeces, and RS3 (retrograded starch from wheat and maize) more propionate. We have concluded that RS2 and RS3 are broken down in the human gut, probably in the colon although in 26% of cases this breakdown was impaired. RS exerts mild laxative properties, predominantly through stimulation of biomass excretion but also through some sparing of NSP breakdown.

Adult↗

Measurement of resistant starch in vitro and in vivo.

The digestibility of the starch in plant foods is highly variable, and is dependent on a number of factors, including the physical structure of both the starch and the food matrix. An in vitro technique has been developed to categorize starch in plant foods according to its likely rate and extent of digestion in the human small intestine. The in vitro method provides values for rapidly digestible starch, slowly digestible starch and resistant starch (RS). In the present study values for the RS content of foods, as measured by the analytical technique, were compared with the recovery of starch from these foods when fed to healthy ileostomates. Nine ileostomy subjects were given a polysaccharide-free diet with a breakfast supplement, on eac of 2 d (two subjects) or 3 d (seven subjects), of biscuits made from wheat, potato or banana flours or from moist-heat-processed wheat or maize flours. RS intakes measured in vitro ranged from 8.5 to 15.0 g/d for the test biscuits, and mean starch recoveries in ileostomy effluent were 100.4 (n5, range 91-106)% of those values, but there was substantial variation between individuals. It is proposed that RS is defined as 'the sum of starch and starch-degradation products that, on average, reach the human large intestine'. The analytical method for the measurement of RS in vitro based on this definition is shown to provide an accurate prediction of the average amount of starch that is likely to escape complete digestion and absorption in the human small intestine.

Adult↗