probiotics, prebiotics and the gut microbiota - International Life ...

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16 Concise Monograph SeriesHEALTH EFFECTSOF PREBIOTICS ANDPROBIOTICSResearch challengesIn order to demonstrate that probiotics and prebioticshave beneficial effects on human health, evidence shouldbe provided by nutritional intervention studies in humansubjects. Supportive evidence may be gathered fromanimal feeding studies (in vivo studies) as well as fromlaboratory studies that examine blood or tissue samplestaken from humans or animals (ex vivo studies), or byexamining isolated cells that are grown in culture in thelaboratory and subject to various experimental conditions(in vitro studies). These non-human studies can provideinsights into mechanisms of action, but are not suitableper se to substantiate a human health benefit.One of the factors that has hampered progress in researchinto the health impact of functional foods, includingprobiotics and prebiotics, is the lack of generally acceptedbiomarkers of GI health and immune function. In thiscontext, biomarkers are surrogate markers of healthendpoints just as blood cholesterol level is a well-acceptedrisk factor of disease. Accepted markers of GI functioninclude stool bulk and the transit time through the GItract, and these can be used to demonstrate the benefitof prebiotics and probiotics. There are numerous markersused in relation to the immune system but knowledge islacking about the predictive value of single markers offunction, such as immune cell function, cytokine levels,or antibody production, in overall immune health. Therelevance of these immune markers remains to beestablished, even when more than one marker is used. Theabsence of agreed markers means that clinical endpointssuch as reduced susceptibility to an infection, enhancedresponse to a vaccine or reduction in the duration ofvalidated symptoms are still more widely accepted asevidence of benefit than are changes in a biomarker.Another challenge that is common to all research in humansis inter-individual variation, i.e. the variability in resultsobserved for a specific endpoint in different subjects. Interindividualvariability depends on a wide range of factorsincluding host genetics, diet, microbiota, age, nutritionalstatus and other lifestyle factors. Researchers try to controlfor these differences but must include sufficient subjectnumbers to allow for variation. In addition, the effects ofan intervention may be more evident in people at high riskof, or diagnosed with, a disease than they are in healthysubjects. This often poses a question as to whether theeffect would be observed in healthy people.In all cases, it is clear that prebiotics and probiotics mustbe consumed regularly in order to confer a benefit.Impact on the GI tract of prebioticsand probioticsGut microbiotaAn increased proportion of bifidobacteria and lactobacilli isthought to represent a “healthier” microbial composition.This is partly based on evidence from infants, which isdiscussed later in this section as well as in the section onmechanisms. These bacteria are more likely to fermentcarbohydrates and produce acids, and they generally lackpotential toxicity.There is ample evidence in human subjects, includinginfants, as well as in animal and in vitro studies thatestablished prebiotics increase the proportion ofbifidobacteria and sometimes lactobacilli present in thegut microbiota while having no measurable effects onother groups of bacteria.
Probiotics, Prebiotics and the Gut Microbiota 17In the case of probiotics, the consumption of adequatedoses of Lactobacillus strains often results in a measurableincrease in the lactobacilli in the faeces, and in somecases there may be a decrease in unfavourable organismssuch as staphylococci. For pre-term infants, who usuallyharbour reduced numbers of bifidobacteria, there isgood evidence that the ingestion of bifidobacteria notonly increases their numbers but may also reduce thenumbers of clostridia. In practice, the effect of prebioticsand probiotics on the microbiota is somewhat variablebut also difficult to measure because of the factorsdiscussed in the section “Techniques for exploring theGI microbiota”.In addition to considering an increase in the number orproportion of certain microbes, it is also important toconsider their functional capacity, which may be changedby prebiotic or probiotic consumption in the absence ofan alteration in number or proportion. Recent humandata on probiotics using new techniques have enabledmeasures of components that reflect the genes thatare being actively expressed at any given time. The linkbetween gene expression and health outcomes will nodoubt be the subject of future research.Transit time and stool bulkingThere is strong evidence that prebiotics and probioticscan influence gut function. This effect for prebiotics isthought to be due to their fermentation in the colon,resulting in increased bacterial mass and osmotic waterbindingcapacity that contribute to increased stoolweight, increased stool frequency and softer stools.There is also some evidence that SCFA, especiallybutyrate, have a positive effect on the endotheliumand on peristalsis, which improves transit. Becausethere is an inverse link between stool mass and transittime, prebiotics may also decrease transit time. In somestudies, prebiotics are reported to reduce symptoms ofintestinal discomfort, such as bloating, abdominal painand flatulence. Studies on certain strains of probioticbacteria have demonstrated an impact on gut function,as revealed by normalisation of transit time and reductionof self-reported minor digestive discomfort symptoms.An improved transit time may reduce putrefactive activityin the left colon, as indicated by some studies that havefound reduced levels of polyamines and metabolitessuch as cresol and indoles.These stool-regulating effects are considered to bebeneficial to gut health by decreasing the risk ofconstipation. An improvement of stool function is likely tobe important with respect to the general population sincedietary fibre intakes in developed countries are almostuniversally lower than recommended and the number ofpeople reporting digestive problems is extremely high(more than 80% in some surveys of women). As withall dietary fibre, too-high an intake of prebiotics mayneed to be avoided by certain individuals because overconsumptioncould lead to bloating and, in severe cases,to watery stools. However, this subsides if consumptionis reduced or stopped.Chronic inflammatory gut conditionsThe inflammatory bowel diseases (IBD) are seriousconditions with an as-yet unknown cause. They includeCrohn’s disease (CD), which can affect the whole gutthough mainly affects the small intestine, and ulcerativecolitis (UC), which is usually restricted to the large bowel.IBD is associated with a breakdown of the normal barrierfunction provided by the gut epithelial lining and itsassociated mucus. Whether the inflammation causes thebreakdown of the barrier or if a breakdown of the barrierallows inflammation to develop is not clear. It is knownfrom studies on germ-free animals compared to normalanimals that germ-free animals are less susceptible toexperimental IBD and that the presence of commensal
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