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

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18 Concise Monograph Seriesbacteria can initiate and/or exacerbate inflammatorybowel conditions. CD and UC may thus result from aninappropriate mucosal immune response to the GImicrobiota in genetically susceptible individuals. There isalso some evidence from clinical studies that the balanceof different groups of commensal bacteria might bealtered in IBD patients.Numerous studies of both probiotics and prebioticsin animal models have shown a positive impact on theprevention or treatment of IBD. Clinical studies in CDsubjects have not been effective in prolonging remissionof CD, but there are promising data indicating thatsome probiotics are useful in maintaining remission inUC. In another inflammatory bowel condition known aspouchitis, which can occur after surgery to treat UC, onemixture of probiotic strains appeared to be effective inhelping maintain remission. The potential for prebioticsand synbiotics to help the management of IBD has beenshown in several small studies with fructans, mainly in thereduction of inflammatory markers, but as yet the datado not allow a final conclusion. Although there are stillinsufficient data to draw firm conclusions on the effect ofpre- or probiotics on IBD, importantly, none of the trialsconducted thus far have raised concerns regarding theirsafety in patients with IBD at the levels of intake tested.Irritable bowel syndromeIrritable bowel syndrome (IBS) is a distressing conditionthat is characterised by an array of symptoms such asabdominal pain, bloating and altered bowel habits thatmay often alternate between constipation and diarrhoea.As similar symptoms can be observed from time to time inthe general population, a specific set of criteria (known asthe Rome criteria) was developed to improve consistencyof diagnosis of IBS. In industrialised countries, IBS affectsbetween about 5 and 20% of the adult population, withrates higher in women and older people. Recently, therehas been interest in the role of inflammatory processes asa potential cause of IBS. In addition, in a certain subset ofsubjects, it appears that previous gut infections play a rolein onset of IBS (post-infectious IBS). Furthermore, in somestudies, lower levels of bifidobacteria have been observedin subjects with IBS compared with healthy subjects.Because of the lack of good therapy for IBS and theidentification of abnormal microbiota in IBS subjects, bothprobiotics and prebiotics have been investigated for theirability to help subjects manage this condition. A coupleof probiotic preparations have been shown to providereduction in a global symptom score (the sum of a numberof different symptom scores) and in reducing abdominalpain; however, no change in diarrhoea, constipation orbloating was confirmed. In other studies, some strainshad no effect or resulted in worsening of symptoms. Forsome prebiotics, studies showed that low doses led toan improvement in the condition, whereas a larger loadled to an enhancement of the perceived symptoms.Thus, additional research will be required to determine ifconsistent benefits can be observed by those experiencingIBS if they use prebiotics and probiotics.Impact on the GI tract specific toprebioticsColon cancerColon cancer has been linked to diets low in dietary fibreand thus the potential for prebiotics to reduce coloncancer risk has also been investigated, mainly usingin vitro techniques and animal models. Results fromanimal studies with endpoints such as DNA damage,aberrant crypt foci as well as tumours in the colonsuggest that prebiotics may reduce the risk of coloncancer. This is supported by ample in vitro evidence.Synbiotics were investigated in a few animal studies andwere found to be more effective than either prebioticsor probiotics alone. One synbiotic study (SYNCAN
Probiotics, Prebiotics and the Gut Microbiota 19project) in humans found a reduction in DNA damageand a reduction in cell proliferation in colon biopsies.Potential mechanisms for a prebiotic effect on coloncancer risk have been identified in animal studies andinclude changes in gut bacterial enzyme activities, whichmodify the fermentation products, and up-regulation ofapoptosis (programmed cell death – in this case of thepre-cancerous cells). However, definitive evidence thatcertain prebiotics might reduce the risk of colon cancerin human subjects is lacking and requires more robust,multi-centre, prospective human trials.Prebiotics in early life nutritionOligosaccharides with fucosyl, galactosyl and sialylstructures are found in human breast milk and arethought to promote healthy microbiota. Interventionstudies show that infant formula supplemented with GOSand fructans, alone or in combination, help stimulate thebifidobacteria that are characteristic of breast-fed infantsin a dose-dependent manner. Further, infants fed formulawith oligosaccharides have microbiota, a stool pH and aSCFA pattern similar to those of breast-fed infants. Thestool consistency and stool frequency of prebiotic-fedinfants (softer and more frequent) is also closer to thatseen for breast-fed infants than for those fed standardformula. The use of specific GOS and fructan prebioticsin infant formula is widespread practice and acceptedas safe. The range of the resulting benefits of theseprebiotics as well as of other prebiotic candidates is stillan active area of research by experts in the field.Mineral absorptionOne specific, well-established effect of prebiotics is onmineral absorption. There is a wealth of data showingthat prebiotics increase calcium absorption and increasegrowth and skeletal mass in rats. In addition, thereare some studies showing enhanced absorption ofmagnesium and iron. Further evidence for an improvedmineral absorption is available from pigs, which areconsidered a better model for the human than are rodents.Numerous human intervention studies consistently showan increase in calcium absorption. So far, there is onelong-term human intervention study that assessed theeffects of prebiotics on bone health. The study was inadolescents and used a combination of FOS and longchaininulin (50/50). After one year, bone mineral densityand bone mineral content were significantly higher atcertain bone sites in the supplemented group. Whetherthis effect is common to all prebiotics or unique to theparticular formulation requires further substance-specificresearch.Gut hormones and food intakeNumerous studies in rodents, mainly with fructans,show a consistent effect of feeding prebiotic fibres inreducing food intake and decreasing fat mass, thoughnot necessarily body weight. Additional data from thesestudies suggests that the mechanism for this is likelyto be SCFA-stimulated secretion of gut peptides suchas glucagon-like peptide (GLP)-1, peptide YY (PYY)and oxytomodulin and reduced secretion of ghrelin,all of which are secreted by endocrine-type cells inthe mucosa. These peptides are known to affect foodintake in animals and humans. Overall, evidence froman increasing number of studies in human subjects,mainly with fructans, supports an effect of daily prebioticconsumption in reducing appetite, lowering body weightor fat mass, altering gut peptide levels in blood andimproving glucose tolerance. Some, but not all, of thesestudies examined the composition of the gut microbiota;where examined, shifts in the microbiota were confirmed.The impact of SCFA on glucose and lipid metabolismmay also be important.
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