Abrams SA et al; Am J Clin Nutr 2005; 82(2): P-471-6

BACKGROUND: Short-term studies in adolescents have generally shown an enhancement of calcium absorption by inulin-type fructans. Results have been inconsistent; however, and no studies have been conducted to determine whether this effect persists with long-term use. OBJECTIVE: The objective was to assess the effects on calcium absorption and bone mineral accretion after 8 wk and 1 y of supplementation with an inulin-type fructan. DESIGN: Pubertal adolescents were randomly assigned to receive 8 g/d of a mixed short and long degree of polymerization inulin-type fructan product (fructan group) or maltodextrin placebo (control group). Bone mineral content and bone mineral density were measured before randomization and after 1 y. Calcium absorption was measured with the use of stable isotopes at baseline and 8 wk and 1 y after supplementation. Polymorphisms of the Fok1 vitamin D receptor gene were determined. RESULTS: Calcium absorption was significantly g reater in the fructan group than in the control group at 8 wk (difference: 8.5 +/- 1.6%; P < 0.001) and at 1 y (difference: 5.9 +/- 2.8%; P = 0.04). An interaction with Fok1 genotype was present such that subjects with an ff genotype had the least initial response to fructan. After 1 y, the fructan group had a greater increment in both whole-body bone mineral content (difference: 35 +/- 16 g; P = 0.03) and whole-body bone mineral density (difference: 0.015 +/- 0.004 g/cm(2); P = 0.01) than did the control group. CONCLUSION: Daily consumption of a combination of prebiotic short- and long-chain inulin-type fructans significantly increases calcium absorption and enhances bone mineralization during pubertal growth. Effects of dietary factors on calcium absorption may be modulated by genetic factors, including specific vitamin D receptor gene polymorphisms.

Chan AT et al; Gastroenterology 2008; 134(1): P-21-8

BACKGROUND & AIMS: Long-term data on the risk of colorectal cancer according to dose, duration, and consistency of aspirin therapy are limited. METHODS: We conducted a prospective study of 47,363 male health professionals who were ages 40-75 years at enrollment in 1986. Biennially, we collected data on aspirin use, other risk factors, and diagnoses of colorectal cancer. We confirmed all reports of colorectal cancer through 2004 by review of medical records. RESULTS: During 18 years of follow-up, we documented 975 cases of colorectal cancer over 761,757 person-years. After adjustment for risk factors, men who regularly used aspirin (>/=2 times per week) had a multivariate relative risk (RR) for colorectal cancer of 0.79 (95% confidence interval, [CI], 0.69-0.90) compared with nonregular users. However, significant risk reduction required at least 6-10 years of use (P for trend = .008) and was no longer evident within 4 years of discontinuing use (multivariat e RR, 1.00; CI, 0.72-1.39). The benefit appeared related to increasing cumulative average dose: compared with men who denied any aspirin use, the multivariate RRs for cancer were 0.94 (CI, 0.75-1.18) for men who used 0.5-1.5 standard aspirin tablets per week, 0.80 (CI, 0.63-1.01) for 2-5 aspirin tablets per week, 0.72 (CI, 0.56-0.92) for 6-14 aspirin tablets per week, and 0.30 (CI, 0.11-0.81) for >14 aspirin tablets per week (P for trend = .004). CONCLUSIONS: Regular, long-term aspirin use reduces risk of colorectal cancer among men. However, the benefit of aspirin necessitates at least 6 years of consistent use, with maximal risk reduction at doses greater than 14 tablets per week. The potential hazards associated with long-term use of such doses should be carefully considered.

Heaney RP; Arq Bras Endocrinol Metabol. 2006; 50(4): P-685

While the fundamental metabolic function of calcium is to serve as a second messenger, coupling intracellular responses to extracellular signals, nutritional deficiency of calcium is manifested at a higher level of organization: 1) depletion of the calcium nutrient reserve; 2) inadequate complexation of digestive byproducts; and 3) collateral effects of hormones produced primarily to compensate for low calcium intake. The first mechanism contributes to the osteoporosis problem, the second to kidney stones and colon cancer, and the third to hypertension, preeclampsia, obesity, and insulin resistance, among others. Adequate calcium intakes (1000-1500 mg/d) in adults have been shown in controlled trials to lower the risk of osteoporotic fractures, kidney stones, obesity, and hypertension. The best source of calcium is dairy foods, largely because the disorders concerned depend upon multiple nutrients, not just calcium, and dairy provides a broad array of essential nu trients in addition to calcium, and at low cost.

Lindsay JO et al; Gut. 2006; 55(3): P-348-55

BACKGROUND AND AIMS: The intestinal microbiota play a pivotal role in the inflammation associated with Crohn's disease through their interaction with the mucosal immune system. Some bifidobacteria species are immunoregulatory and induce increased dendritic cell interleukin 10 (IL-10) release in vitro. Fructo-oligosaccharides (FOS) increase faecal and mucosal bifidobacteria in healthy volunteers. The aim of this study was to assess the effect of FOS administration on disease activity, bifidobacteria concentrations, and mucosal dendritic cell function in patients with moderately active Crohn's disease. PATIENTS AND METHODS: Ten patients with active ileocolonic Crohn's disease received 15 g of FOS for three weeks. Disease activity was measured using the Harvey Bradshaw index. Faecal and mucosal bifidobacteria were quantified by fluorescence in situ hybridisation, and mucosal dendritic cell IL-10 and Toll-like receptor (TLR) expression were assessed by flow cytometry of dissociated rectal biopsies. RESULTS: FOS induced a significant reduction in the Harvey Bradshaw index from 9.8 (SD 3.1) to 6.9 (3.4) (p < 0.01). There was a significant increase in faecal bifidobacteria concentration from 8.8 (0.9) log(10) to 9.4 (0.9) log(10) cells/g dry faeces (p < 0.001). The percentage of IL-10 positive dendritic cells increased from 30 (12)% to 53 (10)% (p=0.06). Finally, the percentage of dendritic cells expressing TLR2 and TLR4 increased from 1.7 (1.7)% to 36.8 (15.9)% (p=0.08) and from 3.6 (3.6)% to 75.4 (3.4)% (p < 0.001), respectively. CONCLUSIONS: FOS supplementation increases faecal bifidobacteria concentrations and modifies mucosal dendritic cell function. This novel therapeutic strategy appears to decrease Crohn's disease activity in a small open label trial and therefore warrants further investigation.

Roediger WE et al; Dig Dis Sci. 1997; 42(8): P-1571-9

A role for colonic sulfide in the pathogenesis and treatment of ulcerative colitis (UC) has emerged based on biochemical, microbiological, nutritional, toxicological, epidemiological, and therapeutic evidence. Metabolism of isolated colonic epithelial cells has indicated that the bacterial short-chain fatty acid n-butyrate maintains the epithelial barrier and that sulfides can inhibit oxidation of n-butyrate analogous to that observed in active UC. Sulfur for fermentation in the colon is essential for n-butyrate formation and sulfidogenesis aids disposal of colonic hydrogen produced by bacteria. The numbers of sulfate-reducing bacteria and sulfidogenesis is greater in UC than control cases. Sulfide is mainly detoxified by methylation in colonic epithelial cells and circulating red blood cells. The enzyme activity of sulfide methylation is higher in red blood cells of UC patients than control cases. Patients with UC ingest more protein and thereby sulfur amino acid s than control subjects. Removing foods rich in sulfur amino acids (milk, eggs, cheese) has proven therapeutic benefits in UC. 5-Amino salicylic acid reduces fermentative production of hydrogen sulfide by colonic bacteria, and aminoglycosides, which inhibit sulfate-reducing bacteria, are of therapeutic benefit in active UC. Methyl-donating agents are a category of drugs of potential therapeutic use in UC. A correlation between sulfide production and mucosal immune responses in UC needs to be undertaken. Control of sulfidogenesis and sulfide detoxification may be important in the disease process of UC, although whether their roles is in an initiating or promoting capacity has yet to be determined.

Coxam V; J Nutr. 2007; 137(11 Suppl): P-2527S

In humans, there is increasing evidence that the colon can absorb nutritionally significant amounts of calcium, and this process may be susceptible to dietary manipulation by fermentable substrates, especially inulin-type fructans. Inulin-type fructans can modulate calcium absorption because they are resistant to hydrolysis by mammalian enzymes and are fermented in the large intestine to produce short-chain fatty acids, which in turn reduce luminal pH and modify calcium speciation, and hence solubility, or exert a direct effect on the mucosal transport pathway. Quite a few intervention studies showed an improvement of calcium absorption in adolescents or young adults by inulin-type fructans. In the same way, a positive effect has been reported in older women.

Floch MH, Narayan R; J Clin Gastroenterol 2002; 35(1 Suppl): P-S45-52

Patients with irritable bowel syndrome (IBS) often request dietary recommendations. They must eat, and they want to know what to eat. Present national guidelines recommend dietary treatment with fiber for IBS patients with constipation. Diet recommendations are made based on symptoms. There may be different dietary recommendations for constipation, diarrhea, and pain or bloating. This article reviews the relationship of foods to IBS and issues of food intolerances and hypersensitivities, and recommendations for diet therapy. The role of dietary fiber, both soluble and insoluble, is reviewed. Although there are few studies to substantiate exact diets, broad dietary plans are recommended for the different symptoms of IBS. In addition, the recent literature on probiotics and prebiotics pertinent to IBS is reviewed.

Kim YS, Milner JA; J Nutr. 2007; 137(11 Suppl): P-2576S

Colon cancer remains a significant global health concern. The impact of specific dietary components on colon tissue likely depends on a host of genomic processes that influence the growth, development, and differentiation of the epithelial cells at the colon crypt surface, where the balance between proliferation and differentiation is maintained possibly through the Wnt (beta-catenin/T-cell factor) signaling pathway. A loss of balance caused by either genetic mutations or environmental factors such as dietary habits can modulate the risk for the formation of aberrant crypt foci and ultimately the development of colon cancer. Evidence exists that butyrate reduces the number and the size of aberrant crypt foci in the colon. Butyrate is a natural histone deacetylase inhibitor as well as a molecule involved with enhanced TGF-beta-induced SMAD3 phosphorylation, increased IFN-gamma-mediated apoptosis, and altered expression of the intestinal muc2 gene that is responsibl e for mucin synthesis. Other dietary components, such as vitamin D and (n-3) fatty acids, may regulate proliferative properties of colon progenitor cells as well as the differentiation of subcellular lineages. Although these findings are intriguing, there are uncertainties that remain to be resolved including the optimal exposure needed to bring about an effect, the appropriate timing of administration, and if nutrient-nutrient and nutrient-gene interactions determine the overall response. The expanded use of high-throughput technologies, knowledge about the expression of genes and protein fingerprints, and metabolomic profiling will assist in addressing these issues and ultimately in determining the physiological significance of bioactive food components as cancer protectants.

Scholz-Ahrens KE et al; Am J Clin Nutr. 2001; 73(2 Suppl): P-459S

Nondigestible oligosaccharides (NDOs) have been found to stimulate absorption of several minerals and to improve mineralization of bone. Hence, these substances are potential ingredients for "functional foods." In addition to a nutritional effect, functional foods have physiologic and psychological benefits that result in improved health or reduced risk of chronic disease. Most of the scientific evidence for the functional effects of NDOs is based on animal experiments in which NDOs increased the availability of calcium, magnesium, zinc, and iron. This stimulatory effect of some NDOs is assumed to be mainly due to their prebiotic character. A prebiotic is defined as a substrate or food ingredient that is nondigestible for the host but is fermented selectively by some of the intestinal microflora. Thus, it stimulates the growth and activity of bacteria with beneficial consequences for the host's health. Recently, these findings were confirmed in human studies for s ome NDOs. The effects seem to be specific for the type of carbohydrate and are likely related to the rate of fermentation by the intestinal flora and appear to depend on the ingested dose. Contradictory results of the effect of prebiotics in literature may be due to the experimental design because the effect of NDOs depends on the dose, the time of administration, the content of calcium in the diet, the part of the skeleton investigated, and the age of the subjects studied.

Hedin C et al; Proc Nutr Soc. 2007; 66(3): P-307-15

Human subjects and their enteric microbiota have evolved together to reach a state of mutual tolerance. Mounting evidence from both animal models and human studies suggests that inflammatory bowel disease (IBD) represents a malfunction of this relationship. The enteric microecology therefore represents an attractive therapeutic target with few side effects. Probiotics and prebiotics have been investigated in clinical trials as treatments for IBD, with conflicting results. The evidence for the use of probiotics in the management of pouchitis is persuasive and several studies indicate their effectiveness in ulcerative colitis. Trials of probiotics and prebiotics in Crohn's disease are less convincing. However, methodologies vary widely and a range of probiotic, prebiotic and combination (synbiotic) treatments have been tested in a variety of patient groups with an assortment of end points. Conclusions about any one treatment in a specific patient group can therefore only be drawn on evidence from relatively small numbers of patients. The present article reviews the role of the intestinal microbiota in the pathogenesis of IBD and addresses the clinical evidence for the therapeutic manipulation of bowel microbiota using probiotics, prebiotics and synbiotics in IBD.

Flint HJ et al; Environ Microbiol. 2007; 9(5): P-1101

The microbiota of the human intestinal tract play an important role in health, in particular by mediating many of the effects of diet upon gut health. Surveys of 16S rRNA sequence diversity in the human colon have emphasized the low proportion of sequences that match cultured bacterial species. This may reflect limited recent effort on cultivation rather than inherent unculturability, however, as anaerobic isolation methods can apparently recover a wide range of the diversity found. A combination of information from representative cultures, molecular tools for enumeration and tracking of bacterial metabolites offers the most powerful route to understanding the roles played by different groups of bacteria in the gut ecosystem. Progress is being made for example in defining key functional groups including primary colonizers of insoluble dietary substrates, and major contributors to metabolites such as butyrate that influence the health of the gut mucosa. There is in creasing evidence that bacterial populations in the large intestine respond to changes in diet, in particular to the type and quantity of dietary carbohydrate. A general consequence of increased carbohydrate consumption is to reduce the pH of the gut lumen, which is likely to play a major role in determining bacterial metabolism and competition. Oligosaccharides used as dietary prebiotics must inevitably have complex effects upon the bacterial community that include non-target organisms and the consequences of metabolic cross-feeding and changes in the gut environment.

Katharina E. Scholz-Ahrens, Jürgen Schrezenmeir ; J Nutr. 2007; 137: 2513S

Nondigestible oligosaccharides have been shown to increase the absorption of several minerals (calcium, magnesium, in some cases phosphorus) and trace elements (mainly copper, iron, zinc). Inulin-type fructans including oligofructose and fructooligosaccharides derived from sucrose by enzymatic transfructosylation are the best investigated food ingredients in this respect. The stimulation of absorption was more pronounced when the demand for calcium was high, i.e., in animals in the rapid growing stage and in animals with impaired calcium absorption because of either ovariectomy or gastrectomy. Even a small stimulation of calcium absorption increased the mineral accumulation in the skeleton because of its persisting effect over months. Inulin-type fructans stimulated mineral absorption and bone mineral accretion when combined with probiotic lactobacilli and in the presence of antibiotics. Direct comparison of different inulin-type fructans revealed a more pronounced effect by inulin or a mixture of long-chain inulin and oligofructose than by oligofructose alone. Mechanisms on how inulin-type fructans mediate this effect include acidification of the intestinal lumen by short-chain fatty acids increasing solubility of minerals in the gut, enlargement of the absorption surface, increased expression of calcium-binding proteins mainly in the large intestine, modulated expression of bone-relevant cytokines, suppression of bone resorption, increased bioavailability of phytoestrogens, and, via stimulation of beneficial commensal microorganisms, increase of calcium uptake by enterocytes. Under certain conditions, inulin-type fructans may improve mineral absorption by their impact on the amelioration of gut health including stabilization of the intestinal flora and reduction of inflammation. The abundance of reports indicate that inulin-type fructans are promising substances that could help to improve the supply with available calcium in human nutrition and by this contribute to bone health.

Leenen CH, Dieleman LA; J Nutr. 2007; 137(11 Suppl): P-2572S

Crohn's disease and ulcerative colitis, also called chronic inflammatory bowel diseases (IBD), affect up to 500 per 100,000 persons in the Western world. Recent studies in the etiology of IBD suggest that these diseases are caused by a combination of genetic, environmental, and immunological factors. Results from humans and especially animal models of colitis reported by our group and others have indicated that these diseases result from a lack of tolerance to resident intestinal bacteria in genetically susceptible hosts. Probiotic bacteria have health-promoting effects for the host when ingested and have also shown efficacy in ulcerative colitis and refractory pouchitis. In light of the efficacy of providing probiotic bacteria to patients with IBD, there has been interest in the prophylactic and therapeutic potential of inulin, oligofructose, and other prebiotics for patients with or at risk of IBD. Prebiotics are nondigestible dietary oligosaccharides that affec t the host by selectively stimulating growth, activity, or both of selective intestinal (probiotic) bacteria. Prebiotics are easy to administer and, in contrast to probiotic therapy, do not require administration of large amounts of (live) bacteria and are therefore easier to administer. Studies using prebiotics, especially beta-fructan oligosaccharides, for the treatment of chronic intestinal inflammation have shown benefit in animal models of colitis. Studies using these prebiotics alone or in combination with probiotics are emerging and have shown promise. These dietary therapies could lead to novel treatments for these chronic debilitating diseases.

Stephanie Seifert and Bernhard Watzl; J Nutr. 2007; 137: 2563S

Diet modulates immune functions in different ways and affects host resistance to infections. In addition to the essential nutrients in food, nonessential food constituents such as nondigestible carbohydrates also affect the immune system. First results from human intervention studies suggest that the intake of inulin (IN) and oligofructose (OF) has beneficial effects on the gut-associated lymphoid tissue. At the level of the systemic immune system, however, only minor effects have been observed in healthy adult human subjects. In contrast, data from studies with infants suggest that supplementation with a prebiotic mixture positively affects postnatal immune development and increases fecal secretory IgA. Animal studies confirm the observations from human trials and give more insight into the immune tissue- specific effects of IN/OF. A clear outcome of the animal studies is that the intestinal immune system and especially the immune cells associated with the Peyer's patches are responsive to a dietary supplement of IN/OF and/or their metabolites. The mechanisms of IN/OF include indirect effects such as a shift in the composition of the intestinal flora and the enhanced production of immunoregulatory SCFA and perhaps other bacterial metabolites. Few data suggest direct effects of IN/OF via carbohydrate receptors on intestinal epithelial cells and immune cells. In conclusion, prebiotic IN/OF clearly modulate immunological processes at the level of the gut-associated lymphoid tissue, which may be associated with significant health benefits in infants and patients with intestinal inflammatory diseases.

Blaut M, Clavel T; J Nutr. 2007; 137(3 Suppl 2): P-751S-5S

The bacteria colonizing the human intestinal tract exhibit a high phylogenetic diversity that reflects their immense metabolic potential. By virtue of their catalytic activity, the human gut micro-organisms have an impact on gastrointestinal function and host health. All dietary components that escape digestion in the small intestine are potential substrates of the bacteria in the colon. The bacterial conversion of carbohydrates, proteins and nonnutritive compounds such as polyphenolic substances leads to the formation of a large number of compounds that may have beneficial or adverse effects on human health.

O'keefe SJ; Curr Opin Gastroenterol. 2008; 24(1): P-51

PURPOSE OF REVIEW: To highlight mechanisms whereby diet affects colonic function and disease patterns. RECENT FINDINGS: Topical nutrients are preferentially used by the gut mucosa to maintain structure and function. With the colon, topical nutrients are generated by the colonic microbiota to maintain mucosal health. Most importantly, short chain fatty acids control proliferation and differentiation, thereby reducing colon cancer risk. In patients with massive loss of small intestine, short chain fatty acid production supports survival by releasing up to 1000 kcal energy/day. Human studies show that the microbiota synthesizes a large pool of utilizable folate which may support survival in impoverished populations. Unfortunately, the microbiota may also elaborate toxic products from food residues such as genotoxic hydrogen sulfide by sulfur-reducing bacteria in response to a high-meat diet. The employment of culture-free techniques based on 16S regions of DNA has re vealed that our colons harbor over 800 bacterial species and 7000 different strains. Evidence suggests that the diet directly influences the diversity of the microbiota, providing the link between diet, colonic disease, and colon cancer. The microbiota, however, can determine the efficiency of food absorption and risk of obesity. SUMMARY: Our investigations have focused on a small number of bacterial species: characterization of microbiota and its metabolism can be expected to provide the key to colonic health and disease.

Sofia Kolida, Glenn R. Gibson; J Nutr. 2007; 137: 2503S

The human gut microbiota plays a significant role in human health through its ability to digest food ingredients and manufacture metabolites. This can be positive or negative for host welfare. Moreover, the microflora plays an active role in host defense whereby colonization resistance affords protection against pathogens. Prebiotics are nondigestible food ingredients that target beneficial components of the gut microflora (mainly colonic), particularly the bifidobacteria. In vitro and in vivo evidence has accumulated to confirm the prebiotic effects of inulin-derived fructans.

Guarner F; Br J Nutr. 2007; 137(Suppl 1): P-S85-9

In genetically susceptible individuals, an altered mucosal immune response against some commensal bacteria of the gut ecosystem appears to be the principal mechanism leading to intestinal lesions in inflammatory bowel disease (IBD). The information currently available does not provide an exact explanation about the origin of this important dysfunction of the interaction between host and commensal bacteria, but an altered microbial composition has been detected in the gut ecosystem of patients with Crohn's disease or ulcerative colitis. Prebiotics are food ingredients not digested nor absorbed in the upper intestinal tract that are fermented by intestinal bacteria in a selective way promoting changes in the gut ecosystem. Experimental and human studies have shown that inulin and oligofructose stimulate saccharolysis in the colonic lumen and favour the growth of indigenous lactobacilli and bifidobacteria. These effects are associated with reduced mucosal inflammatio n in animal models of IBD. Strong experimental evidence supports the hypothesis that inulin and oligofructose can offer an opportunity to prevent or mitigate intestinal inflammatory lesions in human Crohn's disease, ulcerative colitis, and pouchitis. Encouraging results have been obtained in preliminary clinical trials.

Katharina E. Scholz-Ahrens et al; J Nutr. 2007; 137: 838S

Several studies in animals and humans have shown positive effects of nondigestible oligosaccharides (NDO) on mineral absorption and metabolism and bone composition and architecture. These include inulin, oligofructose, fructooligosaccharides, galactooligosaccharides, soybean oligosaccharide, and also resistant starches, sugar alcohols, and difructose anhydride. A positive outcome of dietary prebiotics is promoted by a high dietary calcium content up to a threshold level and an optimum amount and composition of supplemented prebiotics. There might be an optimum composition of fructooligosaccharides with different chain lengths (synergy products). The efficacy of dietary prebiotics depends on chronological age, physiological age, menopausal status, and calcium absorption capacity. There is evidence for an independent probiotic effect on facilitating mineral absorption. Synbiotics, i.e., a combination of prebiotics and prebiotics, can induce additional effects. Whether a low content of habitual NDO would augment the effect of dietary prebiotics or synbiotics remains to be studied. The underlying mechanisms are manifold: increased solubility of minerals because of increased bacterial production of short-chain fatty acids, which is promoted by the greater supply of substrate; an enlargement of the absorption surface by promoting proliferation of enterocytes mediated by bacterial fermentation products, predominantly lactate and butyrate; increased expression of calcium-binding proteins; improvement of gut health; degradation of mineral complexing phytic acid; release of bone-modulating factors such as phytoestrogens from foods; stabilization of the intestinal flora and ecology, also in the presence of antibiotics; stabilization of the intestinal mucus; and impact of modulating growth factors such as polyamines. In conclusion, prebiotics are the most promising but also best investigated substances with respect to a bone-health-promoting potential, compared with probiotics and synbiotics. The results are more prominent in animal models, where more studies have been performed, than in human studies, where experimental conditions are more difficult to control.

Marcel Roberfroid ; J Nutr. 2007; 137: 830S

A prebiotic is "a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well-being and health." Today, only 2 dietary nondigestible oligosaccharides fulfill all the criteria for prebiotic classification. The daily dose of the prebiotic is not a determinant of the prebiotic effect, which is mainly influenced by the number of bifidobacteria/g in feces before supplementation of the diet with the prebiotic begins. The ingested prebiotic stimulates the whole indigenous population of bifidobacteria to growth, and the larger that population, the larger is the number of new bacterial cells appearing in feces. The "dose argument" is thus not supported by the scientific data: it is misleading for consumers and should not be allowed. A prebiotic index is proposed, defined as "the increase in the absolute number of bifidobacteria expressed divided by the daily dose of prebiotic ingested."

Fedorak RN, Madsen KL; Curr Opin Gastroenterol. 2004; 20(2): P-146-55

PURPOSE OF REVIEW: This review summarizes the clinical efficacy of probiotics and prebiotics in gastrointestinal disorders and examines the mechanisms of action related to their therapeutic effect. RECENT FINDINGS: The demonstration that immune and epithelial cells can discriminate between different microbial species has extended the known mechanism(s) of action of probiotics beyond simple barrier and antimicrobial effects. It has also confirmed that probiotic bacteria modulate mucosal and systemic immune activity and epithelial function. The progressive unraveling of these mechanisms of action has led to new credence for the use of probiotics and prebiotics in clinical medicine. Level I evidence now exists for the therapeutic use of probiotics in infectious diarrhea in children, recurrent Clostridium difficile-induced infections and postoperative pouchitis. Level II evidence is emerging for the use of probiotics in other gastrointestinal infections, prevention of postoperative bacterial translocation, irritable bowel syndrome, and in both ulcerative colitis and Crohn disease. Nevertheless, one consistent feature has emerged over the past year: Not all probiotic bacteria have similar therapeutic effects. Future clinical trials will need to incorporate this fact into trial planning and design. SUMMARY: The use of probiotics and prebiotics as therapeutic agents for gastrointestinal disorders is rapidly moving into the "mainstream." Mechanisms of action explain the therapeutic effects and randomized; controlled trials provide the necessary evidence for their incorporation into the therapeutic armamentarium.

Michael de Vrese, Philippe R. Marteau; J Nutr. 2007; 137: 803S

Probiotics have preventive as well as curative effects on several types of diarrhea of different etiologies. Prevention and therapy (or alleviation) of diarrhea have been successfully investigated for numerous dietary probiotics to establish probiotic properties and to justify health claims (the medicinal use of probiotic food and the therapy of gastrointestinal diseases itself may not be advertised under current food laws). Other probiotic microorganisms (e.g., Lactobacillus rhamnosus GG, L. reuteri, certain strains of L. casei, L. acidophilus, Escherichia coli strain Nissle 1917, and certain bifidobacteria and enterococci (Enterococcus faecium SF68) as well as the probiotic yeast Saccharomyces boulardii have been investigated with regard to their medicinal use, either as single strains or in mixed-culture probiotics. However, the effects on humans have been assessed mainly in smaller (n < 100) randomized, controlled clinical studies or in open label trials, but large intervention studies and epidemiological investigations of long-term probiotic effects are largely missing. Perhaps with the exception of nosocomial diarrhea or antibiotic-associated diarrhea, the results of these studies are not yet sufficient to give specific recommendations for the clinical use of probiotics in the treatment of diarrhea.

Geier MS et al; Cancer Biol Ther. 2006; 5(10): P-1265-9

Colorectal cancer (CRC) is the third most common form of cancer. Current treatments including chemotherapy, radiotherapy and surgery are all associated with a high risk of complications and are not always successful, highlighting the need to develop new treatment strategies. The ingestion of probiotics, prebiotics or combinations of both (synbiotics) represents a novel new therapeutic option. Probiotics and prebiotics act to alter the intestinal microflora by increasing concentrations of beneficial bacteria such as lactobacillus and bifidobacteria, and reducing the levels of pathogenic micro-organisms. This strategy has the potential to inhibit the development and progression of neoplasia via mechanisms including; decreased intestinal inflammation, enhanced immune function and anti-tumorigenic activity, binding to potential food carcinogens including toxins found in meat products, and a reduction in bacterial enzymes which hydrolyse precarcinogenic compounds, such as beta-glucuronidase. There is substantial experimental evidence to suggest that probiotics and prebiotics may be beneficial in the prevention and treatment of colon cancer, however to date there have been few conclusive human trials. Probiotics and prebiotics have the potential to impact significantly on the development, progression and treatment of colorectal cancer and may have a valuable role in cancer prevention.

Macfarlane S et al; Aliment Pharmacol Ther. 2006; 24(5): P-701-14

BACKGROUND: Prebiotics are short-chain carbohydrates that alter the composition, or metabolism, of the gut microbiota in a beneficial manner. It is therefore expected that prebiotics will improve health in a way similar to probiotics, whilst at the same time being cheaper, and carrying less risk and being easier to incorporate into the diet than probiotics. AIM: To review published evidence for prebiotic effects on gut function and human health. METHODS: We searched the Science Citation Index with the terms prebiotic, microbiota, gut bacteria, large intestine, mucosa, bowel habit, constipation, diarrhoea, inflammatory bowel disease, Crohn's disease, ulcerative colitis, pouchitis, calcium and cancer, focussing principally on studies in humans and reports in the English language. Search of the Cochrane Library did not identify any clinical study or meta-analysis on this topic. RESULTS: Three (Sources of Prebiotics), oligofructose, galacto-oligosaccharides and lactulose, clearly alter the balance of the large bowel microbiota by increasing bifidobacteria and Lactobacillus numbers. These carbohydrates are fermented and give rise to short-chain fatty acid and intestinal gas; however, effects on bowel habit are relatively small. Randomized-controlled trials of their effect in a clinical context are few, although animal studies show anti-inflammatory effects in inflammatory bowel disease, while calcium absorption is increased. CONCLUSIONS: It is still early days for prebiotics, but they offer the potential to modify the gut microbial balance in such a way as to bring direct health benefits cheaply and safely.

Guamer F; Nutr Hosp. 2007; 22 Suppl 2: P-14

The terms intestinal "microflora" or "microbiota refer to the microbial ecosystem colonizing the gastrointestinal tract. Recently developed molecular biology instruments suggest that a substantial part of bacterial communities within the human gut still have to be described. The relevance and impact of resident bacteria on the host physiology and pathology are, however, well documented. The main functions of intestinal microflora include (1) metabolic activities translating into energy and nutrients uptake, and (2) host protection against invasion by foreign microorganisms. Intestinal bacteria play an essential role in the development and homeostasis of the immune system. Lymphoid follicles within the intestinal mucosa are the main areas for immune system induction and regulation. On the other hand, there is evidence implicating intestinal microbiota in certain pathological processes including multi-organ failure, colon cancer, and inflammatory bowel disease.

Kassinen A et al; Gastroenterology. 2007; 133(1): P-340-2

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a significant gastrointestinal disorder with unknown etiology. The symptoms can greatly weaken patients' quality of life and account for notable economical costs for society. Contribution of the gastrointestinal microbiota in IBS has been suggested. Our objective was to characterize putative differences in gastrointestinal microbiota between patients with IBS and control subjects. These differences could potentially have a causal relationship with the syndrome. METHODS: Microbial genomes from fecal samples of 24 patients with IBS and 23 controls were collected, pooled in a groupwise manner, and fractionated according to their guanine cytosine content. Selected fractions were analyzed by extensive high-throughput 16S ribosomal RNA gene cloning and sequencing of 3753 clones. Some of the revealed phylogenetic differences were further confirmed by quantitative polymerase chain reaction assays on individual sampl es. RESULTS: The coverage of the clone libraries of IBS subtypes and control subjects differed significantly (P < .0253). The samples were also distinguishable by the Bayesian analysis of bacterial population structure. Moreover, significant (P < .05) differences between the clone libraries were found in several bacterial genera, which could be verified by quantitative polymerase chain reaction assays of phylotypes belonging to the genera Coprococcus, Collinsella, and Coprobacillus. CONCLUSIONS: The study showed that fecal microbiota is significantly altered in IBS. Further studies on molecular mechanisms underlying these alterations are needed to elucidate the exact role of intestinal bacteria in IBS.

Hou JK, et al.
Am J Gastroenterol 2011 Apr;106(4):563-73.
Conclusions: High dietary intakes of total fats, PUFAs (polyunsaturated fatty acids), omega-6 fatty acids, and meat were associated with an increased risk of CD (Crohn’s Disease) and UC (Ulcerative Colitis).  High fiber and fruit intakes were associated with decreased CD risk, and high vegetable intake was associated with decreased UC risk.

Swidskinski A, et al.
Inflamm Bowel Dis 2009 Mar; 15(3):359-64.
Conclusions: The emulsifier carboxy methyl cellulose (CMC) induces bacterial overgrowth and small bowel inflammation in susceptible animals.  Because of its ubiquity in products and its unrestricted use in food of the industrial world, CMC is an ideal suspect to account for the rise of IBD (inflammatory bowel disease) in the 20th century.

Roberts CL, et al.
Gut, 2010 Oct;59(10):1331-9 Epub 2010 Sep 2
Conclusions: Translocation of E coli (bacteria) across M-cells (intestinal mucous cells) is reduced by soluble plant fibres, such as inulin and oligofructose (Prebiotin), particularly plantain (bananas) and broccoli, but increased by the emulsifier Polysorbate-80.  These effects occur at relevant concentrations (meaning concentrations that are used in the typical prepared foods) and may contribute to the impact of dietary factors or Crohn’s disease pathogenesis.