Does digestibility of meat protein help explain large bowel cancer risk?

Silvester, K R; Cummings, John H.

doi:10.1080/01635589509514417

Cited by 99 publications

(57 citation statements)

References 46 publications

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“…Anaerobic degradation of undigested or endogenous protein in the colon by the resident microbiota, a process also called putrefaction, is generally presumed to be detrimental for the host's health [1][2][3][4][5]. Protein fermentation results in the production of a wide range of metabolites that are in direct contact with the colonic mucosa and can directly interact with the mucosal cells.…”

Section: Introductionmentioning

confidence: 99%

Relevance of protein fermentation to gut health

Windey

Preter

Verbeke

2011

Molecular Nutrition Food Res

515

349

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It is generally accepted that carbohydrate fermentation results in beneficial effects for the host because of the generation of short chain fatty acids, whereas protein fermentation is considered detrimental for the host's health. Protein fermentation mainly occurs in the distal colon, when carbohydrates get depleted and results in the production of potentially toxic metabolites such as ammonia, amines, phenols and sulfides. However, the effectivity of these metabolites has been established mainly in in vitro studies. In addition, some important bowel diseases such as colorectal cancer (CRC) and ulcerative colitis appear most often in the distal colon, which is the primary site of protein fermentation. Finally, epidemiological studies revealed that diets rich in meat are associated with the prevalence of CRC, as is the case in Western society. Importantly, meat intake not only increases fermentation of proteins but also induces increased intake of fat, heme and heterocyclic amines, which may also play a role in the development of CRC. Despite these indications, the relationship between gut health and protein fermentation has not been thoroughly investigated. In this review, the existing evidence about the potential toxicity of protein fermentation from in vitro animal and human studies will be summarized.

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Section: Introductionmentioning

confidence: 99%

Relevance of protein fermentation to gut health

Windey

Preter

Verbeke

2011

Molecular Nutrition Food Res

515

349

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“…Conditions for bacterial growth and metabolism in the human large intestine vary with diet and with location in the colon (8,9,25,38,52). We have little reliable information, however, on the likely impact of dietary and environmental factors on the microbial community of the human colon.…”

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confidence: 99%

pH and Peptide Supply Can Radically Alter Bacterial Populations and Short-Chain Fatty Acid Ratios within Microbial Communities from the Human Colon

Walker¹,

Duncan²,

Leitch³

et al. 2005

Appl Environ Microbiol

635

518

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The effects of changes in the gut environment upon the human colonic microbiota are poorly understood. The response of human fecal microbial communities from two donors to alterations in pH (5.5 or 6.5) and peptides (0.6 or 0.1%) was studied here in anaerobic continuous cultures supplied with a mixed carbohydrate source. Final butyrate concentrations were markedly higher at pH 5.5 (0.6% peptide mean, 24.9 mM; 0.1% peptide mean, 13.8 mM) than at pH 6.5 (0.6% peptide mean, 5.3 mM; 0.1% peptide mean, 7.6 mM). At pH 5.5 and 0.6% peptide input, a high butyrate production coincided with decreasing acetate concentrations. The highest propionate concentrations (mean, 20.6 mM) occurred at pH 6.5 and 0.6% peptide input. In parallel, major bacterial groups were monitored by using fluorescence in situ hybridization with a panel of specific 16S rRNA probes. Bacteroides levels increased from ca. 20 to 75% of total eubacteria after a shift from pH 5.5 to 6.5, at 0.6% peptide, coinciding with high propionate formation. Conversely, populations of the butyrate-producing Roseburia group were highest (11 to 19%) at pH 5.5 but fell at pH 6.5, a finding that correlates with butyrate formation. When tested in batch culture, three Bacteroides species grew well at pH 6.7 but poorly at pH 5.5, which is consistent with the behavior observed for the mixed community. Two Roseburia isolates grew equally well at pH 6.7 and 5.5. These findings suggest that a lowering of pH resulting from substrate fermentation in the colon may boost butyrate production and populations of butyrate-producing bacteria, while at the same time curtailing the growth of Bacteroides spp.Microbial metabolism in the colon has an important impact on health and is strongly influenced by the amount and type of dietary components that survive small intestinal digestion. Short-chain fatty acids (SCFA) arising from microbial fermentation provide energy sources for the colonic epithelium, and butyrate in particular exerts important effects on cell differentiation and gut health (2,6,30,44,48,50). Products of microbial fermentation, however, can also be toxic or carcinogenic (21). Shifts in microbial community structure caused by diet (32) also have the potential to influence interactions between gut microbes, gut epithelial cells, and the immune system (10,28,40).Conditions for bacterial growth and metabolism in the human large intestine vary with diet and with location in the colon (8, 9, 25, 38, 52). We have little reliable information, however, on the likely impact of dietary and environmental factors on the microbial community of the human colon. The pH of the gut lumen is likely to be a key factor. Several reports indicate that a slightly acidic pH can occur in the proximal colon, increasing distally (4, 38, 46). A major factor tending to reduce colonic pH is the production of SCFA by microbial fermentation of dietary carbohydrate energy sources, including prebiotics, that are digestible by gut microorganisms but not by host enzymes (4,18,20). Another key factor that must...

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“…The amount of N entering the large bowel (mainly in the form of protein, peptides and amino acids) can be increased by increasing protein intake (Silvester & Cummings, 1995). There are many different types of proteolytic bacteria found in the large bowel which, depending on pH and substrate availability, may respond to active carbohydrate fermentation in the right colon, or to protein released from bacterial cell lysis in the left colon when readily-fermented carbohydrates, such as pectin, are exhausted (Macfarlane & Cummings, 1991).…”

Section: Meat and Nitrogen Metabolism In The Colonmentioning

confidence: 99%

High-meat diets and cancer risk

Bingham

1999

Proc. Nutr. Soc.

118

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Up to 80 % of breast, bowel and prostate cancers are attributed to dietary practices, and international comparisons show strong positive associations with meat consumption. Estimates of relative risk obtained from cohort investigations are in the same direction, although generally weak, and red and processed meats rather than white meat seem to be associated with elevated risk of colon cancer. In breast cancer, there are consistent associations with total meat intake and there is evidence of a dose response. Despite these associations with meat, existing studies suggest that vegetarians do not have reduced risk of breast, bowel or prostate cancer, but there are no quantitative estimates of amounts of meat consumed by meat eaters in these cohort studies. Possible mechanisms underlying epidemiological associations include the formation of heterocyclic amines in meat when it is cooked. These heterocyclic amines require acetylation by P450 enzymes, and individuals with the fast-acetylating genotype who eat high amounts of meat may be at increased risk of large-bowel cancer. NH 3 and N-nitroso compounds (NOC) formed from residues by bacteria in the large bowel are probably also important. NH 3 is a promotor of large-bowel tumours chemically induced by NOC, and some of the chromosomal mutations found in human colo-rectal cancer are consistent with effects of NOC and heterocyclic amines. However, the type, amount, and cooking method of meat or protein associated with increased risk are not certain. The effects of high levels of meat on NH 3 and NOC output are not reduced by increasing the amount of fermentable carbohydrate in the diet, but interaction between meat, NSP and vegetable intakes on the risk of cancer has not been studied comprehensively. The interaction between dietary low-penetrance genetic polymorphic and somatic mutation factors has also been investigated to a limited extent. Current Department of Health (1998) recommendations are that meat consumption should not rise, and that consumers at the top end of the distribution should consider a reduction in intakes.

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Does digestibility of meat protein help explain large bowel cancer risk?

Cited by 99 publications

References 46 publications

Relevance of protein fermentation to gut health

Relevance of protein fermentation to gut health

pH and Peptide Supply Can Radically Alter Bacterial Populations and Short-Chain Fatty Acid Ratios within Microbial Communities from the Human Colon

High-meat diets and cancer risk

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