Prebiotics: Definition and protective mechanisms Valcheva, Rosica, PhD; Dieleman, Levinus A., PhD, MD
Baillière's best practice & research. Clinical gastroenterology,
02/2016, Letnik:
30, Številka:
1
Journal Article
Recenzirano
Abstract The increase in chronic metabolic and immunologic disorders in the modern society is linked to major changes in the dietary patterns. These chronic conditions are associated with intestinal ...microbiota dysbiosis where important groups of carbohydrate fermenting, short-chain fatty acids-producing bacteria are reduced. Dietary prebiotics are defined as a selectively fermented ingredients that result in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health. Application of prebiotics may then restore the gut microbiota diversity and activity. Unlike the previously accepted prebiotics definition, where a limited number of bacterial species are involved in the prebiotic activity, new data from community-wide microbiome analysis demonstrated a broader affect of the prebiotics on the intestinal microbiota. These new findings require a revision of the current definition. In addition, prebiotics may exert immunomodulatory effects through microbiota-independent mechanisms that will require future investigations involving germ-free animal disease models.
Celiac disease (CeD) is an immune-mediated enteropathy, and unique in that the specific trigger is known: gluten. The current mainstay of therapy is a gluten-free diet (GFD). As novel therapies are ...being developed, complementary strategies are also being studied, such as modulation of the gut microbiome. The gut microbiota is involved in the initiation and perpetuation of intestinal inflammation in several chronic diseases. Intestinal dysbiosis has been reported in CeD patients, untreated or treated with GFD, compared to healthy subjects. Several studies have identified differential bacterial populations associated with CeD patients and healthy subjects. However, it is still not clear if intestinal dysbiosis is the cause or effect of CeD. Probiotics have also been considered as a strategy to modulate the gut microbiome to an anti-inflammatory state. However, there is a paucity of data to support their use in treating CeD. Further studies are needed with therapeutic microbial formulations combined with human trials on the use of probiotics to treat CeD by restoring the gut microbiome to an anti-inflammatory state.
Epidemiological and experimental studies have suggested that diet is one of the environmental factors that contributes to the onset and pathophysiology of ulcerative colitis. Although many patients ...suffering from ulcerative colitis attribute their symptoms or disease relapse to dietary factors, only a few well-designed randomized controlled trials have been done to investigate the role of diet in the management of ulcerative colitis. Here, we review the potential mechanisms of the relationship between diet and pathogenesis of ulcerative colitis and summarize randomized controlled dietary interventions that have been conducted in ulcerative colitis patients.
No previous investigation has summarized findings from prospective cohort studies on the association between dietary intake of fiber, fruit, and vegetables and risk of inflammatory bowel disease ...(IBD). Dietary fiber and its major sources can influence the risk of IBD by modulation of the gut microbiota. This study summarizes findings from published cohort studies on the association between dietary fiber, fruit, and vegetable consumption and risk of IBD. Relevant articles published up to January 2019 were searched via PubMed, MEDLINE, Scopus, Embase, Cochrane Library, and Google Scholar. All prospective cohort studies investigating the association between dietary fiber, fruit, and vegetable intake and risk of IBD were included. Combining 7 effect sizes from 6 studies, no significant association was found between dietary intake of fiber and risk of ulcerative colitis (UC) (RR: 1.09; 95% CI: 0.88, 1.34). However, a significant inverse association was found between dietary fiber intake and risk of Crohn disease (CD) (RR: 0.59; 95% CI: 0.46, 0.74), based on 5 studies with 6 effect sizes. Pooling information from 4 studies, we found a significant protective association between dietary intake of fruit and risk of UC (RR: 0.69; 95% CI: 0.55, 0.86) and CD (RR: 0.47; 95% CI: 0.38, 0.58). We also found a significant inverse association between vegetable consumption and risk of UC (RR: 0.56; 95% CI: 0.48, 0.66) and CD (RR: 0.52; 95% CI: 0.46, 0.59). In conclusion, dietary intake of fruit and vegetables was inversely associated with risk of IBD and its subtypes. Dietary fiber intake was also inversely associated with incidence of IBD and CD, but not with UC. Further studies are warranted to examine the association of other fiber-rich foods with IBD.
Probiotics and prebiotics in ulcerative colitis Derikx, Lauranne A.A.P., MD; Dieleman, Levinus A., MD, PhD; Hoentjen, Frank, MD, PhD
Baillière's best practice & research. Clinical gastroenterology,
02/2016, Letnik:
30, Številka:
1
Journal Article
Recenzirano
Abstract The intestinal microbiota is one of the key players in the etiology of ulcerative colitis. Manipulation of this microflora with probiotics and prebiotics is an attractive strategy in the ...management of ulcerative colitis. Several intervention studies for both the induction and maintenance of remission in ulcerative colitis patients have been performed. Most of these studies evaluated VSL#3 or E. Coli Nissle 1917 and in general there is evidence for efficacy of these agents for induction and maintenance of remission. However, studies are frequently underpowered, lack a control group, and are very heterogeneous investigating different probiotic strains in different study populations. The absence of well-powered robust randomized placebo-controlled trials impedes the widespread use of probiotics and prebiotics in ulcerative colitis. However, given the promising results that are currently available, probiotics and prebiotics may find their way to the treatment algorithm for ulcerative colitis in the near future.
Rapid progress has been made to understand the pathophysiology of inflammatory bowel diseases and to identify new treatments. Interaction of the gut microbiota on the host inflammatory response has ...suggested that alternative therapies, such as probiotics, might have a complementary role in treating and preventing disease flares. Multiple probiotics and their formulations have been studied for both the induction and maintenance of remission of ulcerative colitis (UC); however, mainly Escherichia coli Nissle 1917 and VSL#3 have been shown to provide significant benefits for the prevention and treatment of mild to moderate UC. Although these data are promising, there is still a paucity of robust, randomized-controlled trials to suggest that probiotics be utilized as part of a standard treatment regimen. With continued research and a movement toward carefully selected, individualized management based on an individual's specific microbiota composition and function, probiotics may become an integral part of tailored therapy for UC.
The intestinal microbiota is involved in ulcerative colitis (UC) pathogenesis. Prebiotics are hypothesized to improve health through alterations to gut microbiota composition and/or activity. Our aim ...was therefore to determine if inulin-type fructans induce clinical benefits in UC, and identify if benefits are linked to compositional and/or functional shifts of the luminal (fecal) and mucosal (biopsy) bacterial communities. Patients (n = 25) with mild/moderately active UC received 7.5 g (n = 12) or 15 g (n = 13) daily oral oligofructose-enriched inulin (Orafti®Synergy1) for 9 weeks. Total Mayo score, endoscopic activity and fecal calprotectin were assessed. Fecal and mucosal bacterial communities were characterized by 16S rRNA tag sequencing, and short chain fatty acids (SCFA) production were measured in fecal samples. Fructans significantly reduced colitis in the high-dose group, with 77% of patients showing a clinical response versus 33% in the low-dose group (P = 0.04). Fructans increased colonic butyrate production in the 15 g/d dose, and fecal butyrate levels were negatively correlated with Mayo score (r = −0.50; P = 0.036). The high fructan dose led to an increased Bifidobacteriaceae and Lachnospiraceae abundance but these shifts were not correlated with improved disease scores. In summary, this pilot study revealed that 15 g/d dose inulin type fructans in UC produced functional but not compositional shifts of the gut microbiota, suggesting that prebiotic-induced alterations of gut microbiota metabolism are more important than compositional changes for the benefits in UC. The findings warrant future well-powered controlled studies for the use of β-fructans as adjunct therapy in patients with active UC.
Non-digestible oligosaccharides (NDO) were shown to reduce inflammation in experimental colitis, but it remains unclear whether microbiota changes mediate their colitis-modulating effects. This study ...assessed intestinal microbiota and intestinal inflammation after feeding chemically defined AIN-76A or rat chow diets, with or without supplementation with 8 g/kg body weight of fructo-oligosaccharides (FOS) or isomalto-oligosaccharides (IMO). The study used HLA-B27 transgenic rats, a validated model of inflammatory bowel disease (IBD), in a factorial design with 6 treatment groups. Intestinal inflammation and intestinal microbiota were analysed after 12 weeks of treatment. FOS and IMO reduced colitis in animals fed rat chow, but exhibited no anti-inflammatory effect when added to AIN-76A diets. Both NDO induced specific but divergent microbiota changes. Bifidobacteria and Enterobacteriaceae were stimulated by FOS, whereas copy numbers of Clostridium cluster IV were decreased. In addition, higher concentrations of total short-chain fatty acids (SCFA) were observed in cecal contents of rats on rat chow compared to the chemically defined diet. AIN-76A increased the relative proportions of propionate, iso-butyrate, valerate and iso-valerate irrespective of the oligosaccharide treatment. The SCFA composition, particularly the relative concentration of iso-butyrate, valerate and iso-valerate, was associated (P ≤ 0.004 and r ≥ 0.4) with increased colitis and IL-1 β concentration of the cecal mucosa. This study demonstrated that the protective effects of fibres on colitis development depend on the diet. Although diets modified specific cecal microbiota, our study indicates that these changes were not associated with colitis reduction. Intestinal inflammation was positively correlated to protein fermentation and negatively correlated with carbohydrate fermentation in the large intestine.
Intestinal microbiota mediate toxicity of irinotecan (CPT-11) cancer therapies and cause systemic infection after CPT-11-induced loss of barrier function. The intestinal microbiota and their ...functions are thus potential targets for treatment to mitigate CPT-11 toxicity. However, microbiota changes during CPT-11 therapy remain poorly described. This study analysed changes in intestinal microbiota induced by CPT-11 chemotherapy. Qualitative and quantitative taxonomic analyses, and functional analyses were combined to characterize intestinal microbiota during CPT-11-based chemotherapy, and in presence or absence of oral glutamine, a treatment known to reduce CPT-11 toxicity. In the first set of experiments tumour-bearing rats received a dose-intensive CPT-11 regimen (125 mg kg(-1)×3 days), with or without oral glutamine bolus (0.75 g kg(-1)). In a subsequent more clinically-oriented chemotherapy regimen, rats received two cycles of CPT-11 (50 mg kg(-1)) followed by 5-flurouracil (50 mg kg(-1)). The analysis of fecal samples over time demonstrated that tumours changed the composition of intestinal microbiota, increasing the abundance of clostrridial clusters I, XI, and Enterobacteriaceae. CPT-11 chemotherapy increased cecal Clostridium cluster XI and Enterobacteriaceae, particularly after the dose-intensive therapy. Glutamine treatment prevented the reduced abundance of major bacterial groups after CPT-11 administration; i.e. total bacteria, Clostridium cluster VI, and the Bacteroides-group. Virulence factor/toxin genes of pathogenic Escherichia coli and Clostridium difficile were not detected in the cecal microbiota. In conclusion, both colon cancer implantation and CPT-11-based chemotherapies disrupted the intestinal microbiota. Oral glutamine partially mitigated CPT-11 toxicity and induced temporary changes of the intestinal microbiota.
A relationship between ulcerative colitis (UC) and diet has been shown in epidemiological and experimental studies. In a 6-month, open-label, randomized, placebo-controlled trial, adult UC patients ...in clinical remission were randomized to either an “Anti-inflammatory Diet (AID)” or “Canada’s Food Guide (CFG)”. Menu plans in the AID were designed to increase the dietary intake of dietary fiber, probiotics, antioxidants, and omega-3 fatty acids and to decrease the intake of red meat, processed meat, and added sugar. Stool was collected for fecal calprotectin (FCP) and microbial analysis. Metabolomic analysis was performed on urine, serum, and stool samples at the baseline and study endpoint. In this study, 53 patients were randomized. Five (19.2%) patients in the AID and 8 (29.6%) patients in the CFG experienced a clinical relapse. The subclinical response to the intervention (defined as FCP < 150 µg/g at the endpoint) was significantly higher in the AID group (69.2 vs. 37.0%, p = 0.02). The patients in the AID group had an increased intake of zinc, phosphorus, selenium, yogurt, and seafood versus the control group. Adherence to the AID was associated with significant changes in the metabolome, with decreased fecal acetone and xanthine levels along with increased fecal taurine and urinary carnosine and p-hydroxybenzoic acid levels. The AID subjects also had increases in fecal Bifidobacteriaceae, Lachnospiraceae, and Ruminococcaceae. In this study, we found thatdietary modifications involving the increased intake of anti-inflammatory foods combined with a decreased intake of pro-inflammatory foods were associated with metabolic and microbial changes in UC patients in clinical remission and were effective in preventing subclinical inflammation.
PDF
