Simulated gastro-intestinal digestion is widely employed in many fields of food and nutritional sciences, as conducting human trials are often costly, resource intensive, and ethically disputable. As a consequence, in vitro alternatives that determine endpoints such as the bioaccessibility of nutrients and non-nutrients or the digestibility of macronutrients (e.g. lipids, proteins and carbohydrates) are used for screening and building new hypotheses. Various digestion models have been proposed, often impeding the possibility to compare results across research teams. For example, a large variety of enzymes from different sources such as of porcine, rabbit or human origin have been used, differing in their activity and characterization. Differences in pH, mineral type, ionic strength and digestion time, which alter enzyme activity and other phenomena, may also considerably alter results. Other parameters such as the presence of phospholipids, individual enzymes such as gastric lipase and digestive emulsifiers vs. their mixtures (e.g. pancreatin and bile salts), and the ratio of food bolus to digestive fluids, have also been discussed at length. In the present consensus paper, within the COST Infogest network, we propose a general standardised and practical static digestion method based on physiologically relevant conditions that can be applied for various endpoints, which may be amended to accommodate further specific requirements. A frameset of parameters including the oral, gastric and small intestinal digestion are outlined and their relevance discussed in relation to available in vivo data and enzymes. This consensus paper will give a detailed protocol and a line-by-line, guidance, recommendations and justifications but also limitation of the proposed model. This harmonised static, in vitro digestion method for food should aid the production of more comparable data in the future.

/pdf/a-standardised-static-in-vitro-digestion-method-suitable-for-tvm9kgy0s3.pdf

A standardised static in vitro digestion method suitable for food – an international consensus

Background Although tests for occult blood in the feces are widely used to screen for colorectal cancers, there is no conclusive evidence that they reduce mortality from this cause. We evaluated a fecal occult-blood test in a randomized trial and documented its effectiveness. Methods We randomly assigned 46,551 participants 50 to 80 years of age to screening for colorectal cancer once a year, to screening every two years, or to a control group. Participants who were screened submitted six guaiac-impregnated paper slides with two smears from each of three consecutive stools. About 83 percent of the slides were rehydrated. Participants who tested positive underwent a diagnostic evaluation that included colonoscopy. Vital status was ascertained for all participants over 13 years of follow-up. A committee determined causes of death. A single pathologist determined the stage of cancer for each tissue specimen. Differences in mortality from colorectal cancer, the primary study end point, were monitored with the...

Reducing Mortality from Colorectal Cancer by Screening for Fecal Occult Blood

https://www.medpagetoday.com/upload/2008/3/6/CRC.pdf

Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(96)03386-7.pdf

Randomised controlled trial of faecal-occult-blood screening for colorectal cancer

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

Gastrointestinal (GI) pH has been measured in 66 normal subjects using a pH sensitive radiotelemetry capsule passing freely through the gastrointestinal tract. Signals were recorded with a portable solid state receiver and recording system, enabling unconstrained measurements with normal ambulatory activities for up to 48 h during normal GI transit. Capsule position in the gut was monitored by surface location using a directional detector. Gastric pH was highly acidic (range 1.0-2.5) in all subjects. The mean pH in the proximal small intestine was 6.6 (0.5) for the first hour of intestinal recording. By comparison the mean pH in the terminal ileum was 7.5 (0.4) (p less than 0.001). In all subjects there was a sharp fall in pH to a mean of 6.4 (0.4) (p less than 0.001) as the capsule passed into the caecum. Values are means (SD). pH then rose progressively from the right to the left colon with a final mean value of 7.0 (0.7) (p less than 0.001).

https://gut.bmj.com/content/gutjnl/29/8/1035.full.pdf

Measurement of gastrointestinal pH profiles in normal ambulant human subjects.

Randomised, controlled trial of faecal occult blood screening for colorectal cancer. Results for first 107,349 subjects.

Background: Three large randomised trials have shown that screening for colorectal cancer using faecal occult blood (FOB) tests can reduce the mortality from this disease. Two national pilot studies have recently been launched in the UK to investigate the feasibility of population screening for colorectal cancer in the National Health Service. The largest of the randomised trials was conducted in Nottingham and randomised 152 850 individuals between the ages of 45 and 74 years to receive biennial Haemoccult (FOB) test kit (intervention group) or to a control group.

Aims: We have compared the mortality in the intervention group compared with the control group.

Methods: The 152 850 randomised individuals were followed up through local health records and central flagging (Office for National Statistics) over a median follow up period of 11 years.

Results: At a median follow up of 11 years there was a 13% reduction in colorectal cancer mortality (95% confidence interval 3–22%) in the intervention group despite an uptake at first invitation of only approximately 50%. The mortality reduction for those accepting screening was 27%. The reduction in mortality was independent of sex and site of tumour. There was no significant difference in mortality from causes other than colorectal cancer between the intervention and control groups.

Conclusions: Although the reduction in colorectal cancer mortality was sustained, further follow up of this population is required to determine whether a significant reduction in the incidence of colorectal cancer will be achieved.

https://gut.bmj.com/content/gutjnl/50/6/840.full.pdf

Effect of faecal occult blood screening on mortality from colorectal cancer: results from a randomised controlled trial

In a 15 year prospective study of endoscopic surveillance of columnar lined oesophagus, 102 patients with a mean follow up of 54 (12.5) months and total follow up of 462 years have been evaluated. Of all the sets of biopsies taken, 59 in 21 patients were found to exhibit dysplasia or carcinoma. Four male patients had carcinoma of the oesophagus, indicating a 30 times increased risk of development of adenocarcinoma in columnar lined oesophagus. The length of columnar lined oesophagus in subjects with dysplasia was significantly longer as compared with the whole group (p = 0.01) and when compared with the patients without dysplasia (p = 0.005). None of the patients with dysplasia had a columnar lined oesophagus of less than 8 cm. Length of columnar lined oesophagus therefore seems to be a significant risk factor in the development of dysplasia and subsequent carcinoma and intensive follow up of patients with columnar lined oesophagus greater than 8 cm in length is recommended.

https://gut.bmj.com/content/gutjnl/33/9/1155.full.pdf

Jack D. Hardcastle

Papers

Randomised controlled trial of faecal-occult-blood screening for colorectal cancer

Measurement of gastrointestinal pH profiles in normal ambulant human subjects.

Randomised, controlled trial of faecal occult blood screening for colorectal cancer. Results for first 107,349 subjects.

Effect of faecal occult blood screening on mortality from colorectal cancer: results from a randomised controlled trial

Length of Barrett's oesophagus: an important factor in the development of dysplasia and adenocarcinoma.