Critical evaluation of present knowledge

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Each of the foregoing sections has examined in depth one aspect of the science of gastrointestinal physiology and function in relation to probiotics and prebiotics. The following conclusions are derived from the discussions within each section.

9.1. Intestinal microflora

The intestinal microflora has been studied using traditional methods. A current problem is the presence of non-culturable species, which require new methodologies to be developed for their detection and measurement.

The establishment of the normal human intestinal microflora, its components and metabolic activities, requires further study. Similarly, knowledge is needed on the composition and activities of the flora in different ethnic groups, at different ages and in different countries.

Prebiotics and a few probiotics have already been shown to have the potential to modify significantly the composition of the intestinal microflora. In particular, the stimulatory effect of fructosyl prebiotics on the growth of bifidobacteria is well established. Moreover, prebiotics and probiotics are interesting tools with which to study the physiological consequences of changes in metabolic activities following such modification.

9.2. Mucosal function

There is evidence for a strong interaction between the intestinal microflora, gut mucosa and GALT and the functions and dysfunctions of the gastrointestinal tract. It has been shown that probiotics may change the gut mucosal barrier by stabilizing the intestinal mucosa, normalizing intestinal permeability and improving gut immunology. However, there are differences in the function and activity of different probiotics. Another consequence of intake of prebiotics and probiotics is the prevention of overgrowth of pathogenic bacteria and viruses. Taken together, these modifications have been shown to influence the gut barrier system.

Future human studies should consider intestinal immunity and its modulation by resident probiotic bacteria or prebiotic components in more detail. Local release of cytokines induced by inflammatory reactions may amplify adverse reactions to food components within the intestinal tract and other parts of the body.

9.3. Gastrointestinal physiology

Gut bacteria play a role in bowel functions like faecal mass, stool frequency, regulation of colonic pH, production of SCFA and salvage of energy from non-digestible food components. Any modification of the microflora is likely to influence these functions, but most of the results of human studies with pro- and prebiotics are preliminary and yet to be confirmed. In particular, the interaction of probiotics and prebiotics with the endocrine activity of the gut requires investigation.

9.4. Methodology

There is clearly a need for new methodology to measure and characterize the composition of faecal microflora, in particular in large human nutrition studies.

New biomarkers specifically involved with immune responses need to be defined and validated for nutritional studies. Germ-free animals (gnotobiotic mice) offer a model to clarify the specific effect of a bacterial strain or a food component on a given immune response.

Development of early markers of carcinogenesis is urgently required for human intervention studies.

  1. 5. Human studies on health benefits
  2. 5.1. Prebiotics (Table 9). There are currently few reports of well-designed and well-documented human

Table 9. Established and postulated functional effects of currently available prebiotics in human subjects

Table 10. Postulated clinical effects of probiotics

Areas for future research

Established functional effects

Postulated areas for future research

Non-digestibility and low energy value (<9kJ/g)

Stool bulking effect Modulation of the gut flora, promoting bifidobacteria and repressing Clostridia

Prevention of intestinal disorders (IBS, ulcerative colitis) and infections, including diarrhoea Modulation of immune response Prevention of colon carcinogenesis Reduction in serum levels of triacylglycerols and cholesterol Improved bioavailability of minerals (Ca, Mg)

Research on mechanisms

Regulation of intestinal motility. Modulation of intestinal and systemic immune responses. Reduction and protection of radiotherapy-associated intestinal dysfunction. Prevention of intestinal cancers Intestinal microflora effects, immunomodulation effects, competitive exclusion, cholesterol lowering

IBS, irritable bowel syndrome.

intervention studies with prebiotics. Future studies may indicate differences between the effects of prebiotic components. Thus, it is important that each compound is tested separately or in products designed for a particular function.

9.5.2. Probiotics (Table 10). Alleviation of lactose maldigestion symptoms is well characterized for some probiotics. The ability of certain probiotic strains to shorten the duration of rotavirus diarrhoea has been established in several studies. Immunomodulation has been demonstrated for some probiotic strains and one strain has been documented to reduce the recurrence of superficial bladder cancer in human subjects. Novel methodologies are required to provide further data on the mechanisms of competitive exclusion and microflora modification.

For other areas of interest there are still few well-designed and well-conducted human intervention studies with probiotics. There are indications of significant differences between probiotic bacterial genera and species, and between strains of the same species. Thus, it is important that each strain is tested on its own or in products designed for a particular function. Further research is needed on the immune response, intestinal cancer and the mechanisms that underlie probiotic effects.

  1. 5.3. Diet and colon cancer. The major challenge at present is to demonstrate within intervention studies which specific dietary factors are able to decrease the risk of colon cancer. Recurrence of large adenomas, the step prior to cancer, is a promising tool for use in human studies and could be applied to prebiotics, probiotics and synbiotics using functional food products as test products. Colon cancer-related variables need to be carefully characterized in the diet and among the microflora.
  2. 6. Safety

The human consumption of prebiotics and probiotics, at least lactic-acid bacteria, appears to be safe.

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