Functional constipation is a common disorder of the gut-brain interaction characterized by infrequent bowel movements and hard stools, which substantially affects patients’ quality of life. Supplementation with gut microbiome-targeted prebiotics is a promising non-pharmacological alternative to current treatments. In a randomized, double-blind, placebo-controlled, cross-over trial, we investigated the effect of four-week daily 12 g chicory inulin intake in 39 individuals, with functional constipation according to Rome III criteria. We assessed stool frequency and consistency, constipation-related quality of life (PAC-QOL) and symptoms (PAC-SYM), and microbiota composition through 16S rRNA gene sequencing of fecal samples. After inulin intake, we observed larger changes in stool frequency, abdominal symptoms, and particularly social and emotional well-being related to quality of life, compared to placebo. Additionally, relative abundances of putative butyrate-producing Anaerostipes spp. and Coprococcus 1 spp. were higher. Further investigation, however, pointed to a carry-over whereby half of the participants receiving inulin in the first period had the largest improvements in all outcomes during inulin intake. Moreover, these same participants had higher baseline relative abundances of butyrate-producing Faecalibacterium spp. and Roseburia spp., and lower baseline relative abundances of Bifidobacterium spp. In turn, these participants’ microbiota responded more strongly to inulin intake through a stronger increase in the relative abundance of Bifidobacterium spp. and Anaerostipes spp. To address this apparent carry-over induced bias, we analyzed the first period alone as a parallel trial which supported the observed positive effect of inulin, also affirming its established bifidogenic effect. Daily intake of 12 g inulin improves functional constipation by increasing stool frequency, positively affecting abdominal symptoms and well-being, and modulating the gut microbiota towards higher relative abundances of butyrate-producing genera. Ethical approval was obtained from the Cork Research Ethics Committee of the Cork Teaching Hospitals (Reference ECM 4 (v) 01/09/15), and the trial design was retrospectively registered at ClinicalTrials.gov (NCT05447481; 07/2022).
The inherent and diverse capacity of dietary fibres, nondigestible oligosaccharides (NDOs) and prebiotics to modify the gut microbiota and markedly influence health status of the host has attracted rising interest. Research and collective initiatives to determine the composition and diversity of the human gut microbiota have increased over the past decade due to great advances in high-throughput technologies, particularly the 16S ribosomal RNA (rRNA) sequencing. Here we reviewed the application of 16S rRNA-based molecular technologies, both community wide (sequencing and phylogenetic microarrays) and targeted methodologies (quantitative PCR, fluorescent in situ hybridisation) to study the effect of chicory inulin-type fructans, NDOs and specific added fibres, such as resistant starches, on the human intestinal microbiota. Overall, such technologies facilitated the monitoring of microbiota shifts due to prebiotic/fibre consumption, though there are limited community-wide sequencing studies so far. Molecular studies confirmed the selective bifidogenic effect of fructans and galactooligosaccharides (GOS) in human intervention studies. Fructans only occasionally decreased relative abundance of Bacteroidetes or stimulated other groups. The sequencing studies for various resistant starches, polydextrose and beta-glucan showed broader effects with more and different types of gut microbial species being enhanced, often including phylotypes of Ruminococcaceae. There was substantial variation in terms of magnitude of response and in individual responses to a specific fibre or NDO which may be due to numerous factors, such as initial presence and relative abundance of a microbial type, diet, genetics of the host, and intervention parameters, such as intervention duration and fibre dose. The field will clearly benefit from a more systematic approach that will support defining the impact of prebiotics and fibres on the gut microbiome, identify biomarkers that link gut microbes to health, and address the personalised response of an individual's microbiota to prebiotics and dietary fibres.
Inulin is a soluble dietary fibre, also classified as a prebiotic, extracted from chicory roots. The present study aimed to determine the effect of consumption of native chicory inulin on the stool frequency of middle-aged to older adults (40-75 years old) with uncomfortably but not clinically relevant low stool frequency, specified as two to four days without bowel movements per week. Two randomised, double blind, placebo-controlled crossover trials were conducted using similar protocols in differing populations. Trial A was conducted in Amsterdam, The Netherlands and subsequently Trial B was conducted in Newcastle, United Kingdom. Both trials involved supplementation for 5 weeks with 10 g per day of inulin or placebo, a washout period of 2 weeks, and then crossed over to receive the other treatment. In Trial B, faecal gut microbiota composition was assessed using 16S rRNA gene sequencing. In Trial A, which 10 volunteers completed, the stool frequency was significantly increased to an average 4.9 +/- 0.23 (SEM) times per week during inulin periods versus 3.6 +/- 0.25 in the periods with placebo (p = 0.01). In contrast, in Trial B which 20 volunteers completed, there was no significant effect of the inulin on stool frequency (7.5 +/- 2.1 times per week with inulin, 8.1 +/- 3.0 with placebo, p = 0.35). However, many subjects in Trial B had a stool frequency > 5 per week also for the placebo period, in breach of the inclusion criteria. Combining the data of 16 low stool frequency subjects from Trials A and B showed a significant effect of inulin to increase stool frequency from 4.1 to 5.0 per week (p = 0.032). Regarding secondary outcomes, stool consistency was significantly softer with inulin treatment compared to placebo periods, it increased 0.29 on the Bristol stool scale (p = 0.008) when data from all subjects of Trials A and B were combined. No other differences in bowel habit parameters due to inulin consumption were significant. None of the differences in specific bacterial abundance, alpha or beta diversity were significant, however the trends were in directions consistent with published studies on other types of inulin. We conclude that 10 g per day of native chicory inulin can increase stool frequency in subjects with low stool frequency.
Oligofructose is a prebiotic dietary fibre obtained from chicory root inulin. Oligofructose supplementation may affect satiety, food intake, body weight and/or body composition. The aim was to examine the efficacy of oligofructose-supplemented granola bars on the following weight management outcomes: satiety, energy intake, body weight and body composition in overweight or obese adults. In all, fifty-five adults with overweight or obesity (thirty-six females/nineteen males; age: 41 (sd 12) years; 90·6 (sd 11·8) kg; BMI: 29·4 (sd 2·6) kg/m2) participated in a parallel, triple-blind, placebo-controlled intervention. A total of twenty-nine subjects replaced their snacks twice a day with an equienergetic granola bar supplemented with 8 g of oligofructose (OF-Bar). Subjects in the control group (n 26) replaced their snack with a control granola bar without added oligofructose (Co-Bar). Satiety, 24-h energy intake, body weight and body composition (fat mass and waist circumference) were measured at baseline, weeks 6 and 12. In addition, weekly appetite and gastrointestinal side effects were measured. During the intervention, energy intake, body weight and fat mass remained similar in the Co-Bar and OF-Bar groups (all P>0·05). Both groups lost 0·3 (sd 1·2) kg lean mass (P<0·01) and reduced their waist circumference with -2·2 (sd 3·6) cm (P<0·0001) after 12 weeks. The OF-Bar group reported decreased hunger in later weeks of the intervention (P=0·04), less prospective food consumption (P=0·03) and less thirst (P=0·003). To conclude, replacing daily snacks for 12 weeks with oligofructose-supplemented granola bars does not differentially affect energy intake, body weight and body composition compared with a control bar. However, there was an indication that appetite was lower after oligofructose bar consumption.
Inulin-based prebiotics are non-digestible polysaccharides that influence the composition of the gut microbiota in infants and children, notably eliciting a bifidogenic effect with high short chain fatty acid levels. Inulin, a generic term that comprises β-(2,1)-linked linear fructans, is typically isolated from the chicory plant root, and derivatives such as oligofructose and long chain inulin appear to have different physiological properties. The first 1000 days of a child's life are increasingly recognized as a critical timeframe for health also into adulthood, whereby nutrition plays a key role. There is an ever increasing association between nutrition and gut microbiota composition and development, with life health status of an individual. This review summarizes the latest knowledge in the infant gut microbiota from preterms to healthy newborns, as well as in malnourished children in developing countries. The impact of inulin or mixtures thereof on infants, toddlers and young children with respect to intestinal function and immunity in general, is reviewed. Possible benefits of prebiotics to support the gut microbiome of malnourished infants and children, especially those with infections in the developing world, are considered, as well as for the pregnant mothers health. Importantly, novel insights in metabolic programming are covered, which are being increasing recognized for remarkable impact on long term offspring health, and eventual potential beneficial role of prebiotic inulins. Overall increasing findings prompt the potential for gut microbiota-based therapy to support health or prevent the development of certain diseases from conception to adulthood where inulin prebiotics may play a role.
Sufficient dietary fibre intake reduces the risk of several diseases, but the mechanisms linking fibre structure and health effects remain unclear. To analyse the influence of the amount of methyl groups esterified to the backbone, lemon pectins of different degrees of methyl esterification (30, 56, and 74DM) were studied for immune receptor activating potential and epithelial barrier protection. In reporter assays, the pectins demonstrated TLR/MyD88 dependent activation of NF-κB/AP-1, which increased with increasing pectin DM. To analyse the importance of backbone structure, the pectins were enzymatically digested into oligomers, which abrogated TLR activating potential. The 30 and 74DM pectins induced strong protection of the epithelial barrier measured by T84 transepithelial electrical resistance (TEER). These results indicate that activation of immune cells by lemon pectins is TLR dependent, and the intact polymer backbone is indispensable for activation. In addition, DM is a determining factor in activating potential and epithelial barrier protective effects.
This chapter describes the various compounds that can act as prebiotic fibers: their structure, occurrence, production, and physiological effects (health effects) will be presented. The basis for the description is the latest definitions for dietary fibers and for prebiotics. Using as much as possible data from human studies, both the fiber and the prebiotic properties will be described of a variety of compounds. Based on the presented data the latest developments in the area of prebiotics, fibers and gut and immune health will be discussed in more detail as they show best what the potential impact of prebiotics on health of the human host might be.
Beneficial effects of inulin-type fructans are discussed in view of studies that applied the oligosaccharides in colon cancer, chronic inflammatory diseases, vaccination efficacy, and prevention of infection and allergy. In the present paper, we discuss their immunomodulating effects. It is suggested that immunomodulation is elicited through indirect and direct mechanisms. Indirect mechanisms encompass stimulation of growth and activity of lactic acid bacteria, but can also be caused by fermentation products of these bacteria, i.e., short chain fatty acids. Evidence for direct effects on the immune system generally remains to be confirmed. It is suggested that inulin-type fructans can be detected by gut dendritic cells (DCs), through receptor ligation of pathogen recognition receptors (PRRs) such as Toll-like receptors, nucleotide oligomerization domain containing proteins (NODs), C-type lectin receptors, and galectins, eventually inducing pro- and anti-inflammatory cytokines. DCs may also exert antigen presenting capacity toward effector cells, such as B cells, T cells, and natural killer cells locally, or in the spleen. Inulin-type fructans may also ligate PRRs expressed on gut epithelium, which could influence its barrier function. Inulin-type fructans are potent immunomodulating food components that hold many promises for prevention of disease. However, more studies into the mechanisms, dose-effect relations, and structure-function studies are required.
Dietary fiber intake is associated with lower incidence and mortality from disease, but the underlying mechanisms of these protective effects are unclear. We hypothesized that β2→1-fructan dietary fibers confer protection on intestinal epithelial cell barrier function via Toll-like receptor 2 (TLR2), and we studied whether β2→1-fructan chain-length differences affect this process. T84 human intestinal epithelial cell monolayers were incubated with 4 β2→1-fructan formulations of different chain-length compositions and were stimulated with the proinflammatory phorbol 12-myristate 13-acetate (PMA). Transepithelial electrical resistance (TEER) was analyzed by electric cell substrate impedance sensing (ECIS) as a measure for tight junction-mediated barrier function. To confirm TLR2 involvement in barrier modulation by β2→1-fructans, ECIS experiments were repeated using TLR2 blocking antibody. After preincubation of T84 cells with short-chain β2→1-fructans, the decrease in TEER as induced by PMA (62.3 ± 5.2%, P < 0.001) was strongly attenuated (15.2 ± 8.8%, P < 0.01). However, when PMA was applied first, no effect on recovery was observed during addition of the fructans. By blocking TLR2 on the T84 cells, the protective effect of short-chain β2→1-fructans was substantially inhibited. Stimulation of human embryonic kidney human TLR2 reporter cells with β2→1-fructans induced activation of nuclear factor kappa-light-chain-enhancer of activated B cells, confirming that β2→1-fructans are specific ligands for TLR2. To conclude, β2→1-fructans exert time-dependent and chain length-dependent protective effects on the T84 intestinal epithelial cell barrier mediated via TLR2. These results suggest that TLR2 located on intestinal epithelial cells could be a target of β2→1-fructan-mediated health effects.
Dietary fiber intake is associated with lower incidence and mortality from disease, but the underlying mechanisms of these protective effects are unclear. We hypothesized that b 2 / 1-fructan dietary fibers confer protection on intestinal epithelial cell barrier function via Toll-like receptor 2 (TLR2), and we studied whether b 2 / 1-fructan chain-length differences affect this process. T84 human intestinal epithelial cell monolayers were incubated with 4 b 2 / 1-fructan formulations of different chain-length compositions and were stimulated with the proinflammatory phorbol 12-myristate 13-acetate (PMA). Transepithelial electrical resistance (TEER) was analyzed by electric cell substrate impedance sensing (ECIS) as a measure for tight junction–mediated barrier function. To confirm TLR2 involvement in barrier modulation by b 2 / 1-fructans, ECIS experiments were repeated using TLR2 blocking antibody. After preincubation of T84 cells with short-chain b 2 / 1-fructans, the decrease in TEER as induced by PMA (62.3 6 5.2%, P < 0.001) was strongly attenuated (15.2 6 8.8%, P < 0.01). However, when PMA was applied first, no effect on recovery was observed during addition of the fructans. By blocking TLR2 on the T84 cells, the protective effect of short-chain b 2 / 1-fructans was substantially inhibited. Stimulation of human embryonic kidney human TLR2 reporter cells with b 2 / 1-fructans induced activation of nuclear factor kappa-light-chain-enhancer of activated B cells, confirming that b 2 / 1-fructansare specific ligands for TLR2. To conclude, b 2 / 1-fructans exert time-dependent and chain length–dependent protective effects on the T84 intestinal epithelial cell barrier mediated via TLR2. These results suggest that TLR2 located on intestinal epithelial cells could be a target of b 2 / 1-fructan–mediated health effects. J. Nutr. 144: 1002–1008, 2014.
The impact of oligofructose (OF) intake on stool frequency has not been clearly substantiated, while significant gastrointestinal (GI) symptoms have been reported in some individuals. The aim of the present study was to determine the effects of OF on stool frequency and GI symptoms in healthy adults. In an 8-week, randomised, double-blind, parallel-arm study, ninety-eight participants were provided with 16 g OF in yogurt and snack bars (twenty male and thirty female) or matching control foods (seventeen male and thirty-one female), to incorporate, by replacement, into their usual diets. Participants completed a daily online questionnaire recording stool frequency and rating four symptoms: bloating, flatulence, abdominal cramping and noise, each on a Likert scale from '0' for none (no symptoms) to '6' for very severe, with a maximum symptom intensity score of 24 (sum of severities from all four symptoms). Online 24 h dietary recalls were completed during pre-baseline and weeks 4, 6 and 8 to determine fibre intake. When provided with OF foods, fibre intake increased to 24·3 (sem 0·5) g/d from pre-baseline (12·1 (sem 0·5) g/d; P < 0·001). Stool frequency increased with OF from 1·3 (sem 0·2) to 1·8 (sem 0·2) stools per d in males and 1·0 (sem 0·1) to 1·4 (sem 0·1) stools per d in females during intervention weeks compared with pre-baseline (P < 0·05),but did not change for control participants (males: 1·6 (sem 0·2) to 1·8 (sem 0·2); females: 1·3 (sem 0·1) to 1·4 (sem 0·1)). Flatulence was the most commonly reported symptom. Mean GI symptom intensity score was higher for the OF group (3·2 (sem 0·3)) v. control (1·7 (sem 0·1)) (P < 0·01), with few participants reporting above moderate symptoms. No change in symptom intensity occurred over time. Consuming yogurt and snack bars with 16 g OF improves regularity in young healthy adults. However, GI symptoms, resulting from an increase in oligofructose intake, may not diminish with time.
INTRODUCTION:β2→1-fructans are dietary fibers. Main objectives of this study were 1) to demonstrate direct signalling of β2→1-fructans on immune cells, 2) to study whether this is mediated by the pattern recognition receptors Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain-containing proteins (NODs), and 3) to relate the observed effects to the chain length differences in β2→1-fructans.METHODS:Four different β2→1-fructan formulations were characterised for their chain length profile. Human peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with β2→1-fructans, and production of IL-1Ra, IL-1β, IL-6, IL-10, IL-12p70, and TNF-α was analysed. Reporter cells for TLRs and NODs were incubated with β2→1-fructans and analysed for NF-κB/AP-1 activation.RESULTS:Cytokine production in human PBMCs was dose- and chain length-dependent. Strikingly, short chain enriched β2→1-fructans induced a regulatory cytokine balance compared to long chain enriched β2→1-fructans as measured by IL-10/IL-12 ratios. Activation of reporter cells showed that signalling was highly dependent on TLRs and their adapter, myeloid differentiation primary response protein 88 (MyD88). In human embryonic kidney reporter cells, TLR2 was prominently activated, while TLR4, 5, 7, 8, and NOD2 were mildly activated.CONCLUSIONS:β2→1-fructans possess direct signalling capacity on human immune cells. By activating primarily TLR2, and to a lesser extent TLR4, 5, 7, 8, and NOD2, β2→1-fructan stimulation results in NF-κB/AP-1 activation. Chain length of β2→1-fructans is important for the induced activation pattern and IL-10/IL-12 ratios.
Inulins, the β-(2,1)-fructans extracted on industrial scale from chicory roots [1] and present in many other plants [2], are interesting carbohydrates that exhibit a variety of physiological e¬ects and potential health bene…ts. Being nondigestible-the β(2,1)-bond cannot be hydrolyzed in our digestive system-these ingredients are dietary …bers with the associated physiological e¬ects. ´is means that they have a positive e¬ect on bowel habits, as they improve frequency of defecation and stool consistency, and that they may lower serum lipids as other soluble …bers will also do. In addition, they have a low glycemic and insulinemic response and a low caloric value, and may increase feelings of satiety with a possible e¬ect on food and energy intake. Inulin and oligofructose share these important features with many other dietary …bers [3-5]. ´ere is still discussion whether fermentation in the colon is a bene…cial physiological e¬ect, but it becomes now accepted that it is important for colonic health and thus should be considered as a bene…cial e¬ect of …bers [6,7].
Two hundred years ago, Henri Braconnot described a polysaccharide containing a substantial percent of nitrogen, later to be called chitin: that discovery stemmed from investigations on the composition of edible mushrooms and their nutritional value. The present interdisciplinary article reviews the major research topics explored by Braconnot, and assesses their importance in the light of our most advanced knowledge. Thus, the value of fungi, seafoods and insects is described in connection with the significance of the presence of chitin itself in foods, and chitinases in the human digestive system. The capacity of chitin/chitosan to depress the development of microbial pathogens, is discussed in terms of crop protection and food preservation. Other topics cherished by Braconnot, such as the isolation of pectin from a large number of plants, and inulin from the Helianthus tubers, are presented in up-to-date terms. Acids isolated from plants at that early time, led to enormous scientific advancements, in particular the glyoxylic acid and levulinic acid used for the preparation of soluble chitosan derivatives that paved the way to a number of applications. An opportunity to trace the origins of the carbohydrate polymers science, and to appreciate the European scientific heritage. (C) 2011 Elsevier Ltd. All rights reserved.
In this review we will describe the application of inulin for texture improvement in a variety of dairy applications as this is one of the most important application areas. The effects of inulin in these systems as a fat replacer, i.e. how it can be used to mimic the features of fat for mouthfeel and creaminess, and how these effects may be related to changes in rheology of the food system will be described for liquid, semi-solid and solid dairy products.
In rats, oligofructose has been shown to stimulate satiety hormone secretion, reduce energy intake and promote weight loss. The present study aimed to examine the effect of oligofructose supplementation on appetite profiles, satiety hormone concentrations and energy intake in human subjects. A total of thirty-one healthy subjects (ten men and twenty-one women) aged 28 (sem 3) years with a BMI of 24·8 (sem 0·3) kg/m2 were included in a randomised double-blind, cross-over study. The subjects received 10 g oligofructose, 16 g oligofructose or 16 g placebo (maltodextrin) daily for 13 d, with a 2-week washout period between treatments. Appetite profile, active glucagon-like peptide 1 (GLP-1) and peptide YY3-36 (PYY) concentrations and energy intake were assessed on days 0 and 13 of the treatment period. Time × treatment interaction revealed a trend of reduction in energy intake over days 0–13 by oligofructose (P = 0·068). Energy intake was significantly reduced (11 %) over time on day 13 compared with day 0 with 16 g/d oligofructose (2801 (sem 301) v. 3217 (sem 320) kJ, P < 0·05). Moreover, energy intake was significantly lower with 16 g/d oligofructose compared with 10 g/d oligofructose on day 13 (2801 (sem 301) v. 3177 (sem 276) kJ, P < 0·05). Area under the curve (AUC) for GLP-1 on day 13 was significantly higher with 16 g/d oligofructose compared with 10 g/d oligofructose (45 (sem 4) v. 41 (sem 3) pmol/l × h, P < 0·05). In the morning until lunch, AUC0–230 min for PYY on day 13 was significantly higher with 16 g/d oligofructose compared with 10 g/d oligofructose and placebo (409 (sem 35) v. 222 (sem 19) and 211 (sem 20) pg/ml × h, P < 0·01). In conclusion, 16 g/d and not 10 g/d oligofructose may be an effective dose to reduce energy intake, possibly supported by higher GLP-1 and PYY concentrations.
In the present study, the effect of oligofructose (OF) on the modulation of food intake, blood levels and intestinal gene expression of satiety hormones, in combination with a low-and a high-fat diet, was determined in rats. Rats were fed a low (40 g/kg) or a high (200 g/kg) fat purified diet for three weeks. These diets contained either 1% or 6% OF. Food intake was measured daily, while bodyweight of the animals was measured every other day. Postprandial blood levels of glucagon-like peptide-1 (GLP-1), and peptide tyrosine-tyrosine (PYY) were determined by enzyme linked immunosorbent assay (ELISA) and radioimmunoassay (RIA). Colonic gene expression of these hormones was determined by polymerase chain reaction (PCR). OF decreased food and energy intake and attenuated body weight gain. Interestingly, OF attenuated the hyperphagia and the higher body weight gain caused by the high-fat diet. OF increased postprandial plasma concentrations of the satiety hormone PYY, and elevated the expression of both GLP-1 and PYY in the proximal colon. This study indicates that OF decreases energy intake in rats and modulates the plasma concentrations and colonic gene expression of gut hormones involved in satiety regulation.
Inflammation is a stereotypical physiological response to infections and tissue injury; it initiates pathogen killing as well as tissue repair processes and helps to restore homeostasis at infected or damaged sites. Acute inflammatory reactions are usually self-limiting and resolve rapidly, due to the involvement of negative feedback mechanisms. Thus, regulated inflammatory responses are essential to remain healthy and maintain homeostasis. However, inflammatory responses that fail to regulate themselves can become chronic and contribute to the perpetuation and progression of disease. Characteristics typical of chronic inflammatory responses underlying the pathophysiology of several disorders include loss of barrier function, responsiveness to a normally benign stimulus, infiltration of inflammatory cells into compartments where they are not normally found in such high numbers, and overproduction of oxidants, cytokines, chemokines, eicosanoids and matrix metalloproteinases. The levels of these mediators amplify the inflammatory response, are destructive and contribute to the clinical symptoms. Various dietary components including long chain omega-3 fatty acids, antioxidant vitamins, plant flavonoids, prebiotics and probiotics have the potential to modulate predisposition to chronic inflammatory conditions and may have a role in their therapy. These components act through a variety of mechanisms including decreasing inflammatory mediator production through effects on cell signaling and gene expression omega-3 fatty acids, vitamin E, plant flavonoids), reducing the production of damaging oxidants (vitamin E and other antioxidants), and promoting gut barrier function and anti-inflammatory responses (prebiotics and probiotics). However, in general really strong evidence of benefit to human health through anti-inflammatory actions is lacking for most of these dietary components. Thus, further studies addressing efficacy in humans linked to studies providing greater understanding of the mechanisms of action involved are required.