Resistant starch (RS) is starch and products of its small intestinal digestion that enter the large bowel. It occurs for various reasons including chemical structure, cooking of food, chemical modification, and food mastication. Human colonic bacteria ferment RS and nonstarch polysaccharides (NSP; major components of dietary fiber) to short-chain fatty acids (SCFA), mainly acetate, propionate, and butyrate. SCFA stimulate colonic blood flow and fluid and electrolyte uptake. Butyrate is a preferred substrate for colonocytes and appears to promote a normal phenotype in these cells. Fermentation of some RS types favors butyrate production. Measurement of colonic fermentation in humans is difficult, and indirect measures (e.g., fecal samples) or animal models have been used. Of the latter, rodents appear to be of limited value, and pigs or dogs are preferable. RS is less effective than NSP in stool bulking, but epidemiological data suggest that it is more protective against colorectal cancer, possibly via butyrate. RS is a prebiotic, but knowledge of its other interactions with the microflora is limited. The contribution of RS to fermentation and colonic physiology seems to be greater than that of NSP. However, the lack of a generally accepted analytical procedure that accommodates the major influences on RS means this is yet to be established.

Short-Chain Fatty Acids and Human Colonic Function: Roles of Resistant Starch and Nonstarch Polysaccharides

Obesity has become more prevalent in most developed countries over the past few decades, and is increasingly recognized as a major risk factor for several common types of cancer. As the worldwide obesity epidemic has shown no signs of abating, better understanding of the mechanisms underlying obesity-associated cancer is urgently needed. Although several events were proposed to be involved in obesity-associated cancer, the exact molecular mechanisms that integrate these events have remained largely unclear. Here we show that senescence-associated secretory phenotype (SASP) has crucial roles in promoting obesity-associated hepatocellular carcinoma (HCC) development in mice. Dietary or genetic obesity induces alterations of gut microbiota, thereby increasing the levels of deoxycholic acid (DCA), a gut bacterial metabolite known to cause DNA damage. The enterohepatic circulation of DCA provokes SASP phenotype in hepatic stellate cells (HSCs), which in turn secretes various inflammatory and tumour-promoting factors in the liver, thus facilitating HCC development in mice after exposure to chemical carcinogen. Notably, blocking DCA production or reducing gut bacteria efficiently prevents HCC development in obese mice. Similar results were also observed in mice lacking an SASP inducer or depleted of senescent HSCs, indicating that the DCA-SASP axis in HSCs has key roles in obesity-associated HCC development. Moreover, signs of SASP were also observed in the HSCs in the area of HCC arising in patients with non-alcoholic steatohepatitis, indicating that a similar pathway may contribute to at least certain aspects of obesity-associated HCC development in humans as well. These findings provide valuable new insights into the development of obesity-associated cancer and open up new possibilities for its control.

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Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome

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.

/pdf/functional-food-science-and-gastrointestinal-physiology-and-4smhori2o4.pdf

Functional food science and gastrointestinal physiology and function

Background Diabetes has been associated with an increased risk of colorectal cancer in most, but not all, studies. Findings have also been inconclusive with regard to sex and subsite in the colorectum. To resolve these inconsistencies, we conducted a meta-analysis of published data on the association between diabetes and the incidence and mortality of colorectal cancer. Methods We identified studies by a literature search of Medline from January 1, 1966, through July 31, 2005, and by searching the reference lists of pertinent articles. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with a random-effects model. All statistical tests were two-sided. Results Analysis of 15 studies (six case-control and nine cohort studies), including 2 593 935 participants, found that diabetes was associated with an increased risk of colorectal cancer, compared with no diabetes (summary RR of colorectal cancer incidence = 1.30, 95% CI = 1.20 to 1.40), without heterogeneity between studies (P(heterogeneity) = .21). These results were consistent between case-control and cohort studies and between studies conducted in the United States and in Europe. The association between diabetes and colorectal cancer incidence did not differ statistically significantly by sex (summary RR among women = 1.33, 95% CI = 1.23 to 1.44; summary RR among men = 1.29, 95% CI = 1.15 to 1.44; P(heterogeneity) = .26) or by cancer subsite (summary RR for colon = 1.43, 95% CI = 1.28 to 1.60; summary RR for rectum = 1.33, 95% CI = 1.14 to 1.54; P(heterogeneity) = .42). Diabetes was positively associated with colorectal cancer mortality (summary RR = 1.26, 95% CI = 1.05 to 1.50), but there was evidence for heterogeneity between studies (P(heterogeneity) = .04). Conclusions Our findings strongly support a relationship between diabetes and increased risk of colon and rectal cancer in both women and men.

Diabetes Mellitus and Risk of Colorectal Cancer: A Meta-Analysis

A single pass perfusion system was used in anaesthetised, restrained rats to examine the effect of changing the composition of the perfusion fluid on the damage caused to the colonic epithelium by deoxycholic acid. Damage to the colonic surface was monitored with light microscopy, transmission and scanning electron microscopy and with measurements of deoxyribonucleic acid and carbohydrate in the perfusate. New scoring techniques for monitoring alterations in surface epithelium of light microscopy sections were used. The damaging effect of 5 mM deoxycholic acid to the colonic epithelium is inhibited by lowering the pH of the perfusion fluid from 7.9 to 5.5, or by increasing the calcium concentration from 0 to 4 mM. This inhibition is shown to be because of a decreased amount of bile acid in solution. Thus it is not the total concentration of deoxycholic acid in the colon that is responsible for the colonic damage, but the concentration in solution. Although extrapolation to the human situation must be made with caution, the concentration of bile acid in solution in the faecal water may be more relevant to colonic mucosal damage than total bile acid concentration.

https://gut.bmj.com/content/gutjnl/27/11/1320.full.pdf

Effects of calcium and pH on the mucosal damage produced by deoxycholic acid in the rat colon.

Cellular toxicity of fecal water depends on diet

SUMMARY A single passperfusion system was usedinanaesthetised, restrained ratstoexamine theeffect ofchanging thecomposition oftheperfusion fluid on thedamage caused tothecolonic epithelium bydeoxycholic acid. Damagetothecolonic surface was monitored withlight microscopy, transmission andscanning electron microscopy andwithmeasurementsof deoxyribonucleic acid andcarbohydrate intheperfusate. Newscoring techniques formonitoring alterations insurface epithelium oflight microscopy sections were used. Thedamaging effect of 5mM deoxycholic acid tothecolonic epithelium isinhibited bylowering thepHoftheperfusion fluid from7-9to5*5, orbyincreasing thecalcium concentration from 0 to4mM.Thisinhibition is showntobebecause ofa decreased amountofbile acidinsolution. Thusitisnotthetotal concentration ofdeoxycholic acid inthecolon that isresponsible forthecolonic damage, butthe concentration insolution. Although extrapolation tothehumansituation mustbemadewith caution, theconcentration ofbile acidinsolution inthefaecal watermay bemore relevant to colonic mucosal damagethantotal bileacidconcentration.

V. W. S. Eng

Papers

Effects of calcium and pH on the mucosal damage produced by deoxycholic acid in the rat colon.

Cellular toxicity of fecal water depends on diet

Effects ofcalcium andpHon themucosal damage produced bydeoxycholic acid intheratcolon