The gut microbiome is impacted by certain types of dietary fibre. However, the type, duration, and dose needed to elicit gut microbial changes, and whether these changes also influence microbial metabolites, remains unclear. This study investigated the effects of supplementing healthy participants with two types of non-digestible carbohydrates (resistant starch (RS) and polydextrose (PD)), on the stool microbiota and microbial metabolite concentrations in plasma, stool, and urine, as secondary outcomes in the Dietary Intervention Stem Cells and Colorectal Cancer (DISC) Study.

The DISC Study was a double-blind, randomised controlled trial that supplemented healthy participants with RS and/or PD or placebo for 50 days in a 2*2 factorial design. DNA was extracted from stool samples collected pre- and post-intervention, and V4 16S rRNA gene sequencing was used to profile the gut microbiota. Metabolite concentrations were measured in stool, plasma, and urine by high-performance liquid chromatography.

A total of 58 participants with paired samples available were included. After 50 days, no effects of RS or PD were detected on composition of the gut microbiota diversity (alpha- and beta-diversity), on genus relative abundance, or on metabolite concentrations. However, Drichlet’s multinomial mixture clustering-based approach suggests that some participants changed microbial enterotype post-intervention.

The gut microbiome and faecal, plasma, and urinary microbial metabolites were stable in response to a 50-day fibre intervention in middle aged adults. Larger and longer studies, including those which explore the effects of specific fibre sub-types, may be required to determine the relationships between fibre intake, the gut microbiome, and host-health.

There is strong evidence that foods containing dietary fibre protect against colorectal cancer, resulting at least in part from its anti-proliferative properties. This study aimed to investigate the effects of supplementation with two non-digestible carbohydrates, resistant starch (RS) and polydextrose (PD), on crypt cell proliferative state (CCPS) in the macroscopically normal rectal mucosa of healthy individuals. We also investigated relationships between expression of regulators of apoptosis and of the cell cycle on markers of CCPS. Seventy-five healthy participants were supplemented with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design in a randomised, double-blind, placebo-controlled trial (the Dietary Intervention, Stem cells and Colorectal Cancer (DISC) Study). CCPS was assessed, and the expression of regulators of the cell cycle and of apoptosis was measured by quantitative PCR in rectal mucosal biopsies. SCFA concentrations were quantified in faecal samples collected pre- and post-intervention. Supplementation with RS increased the total number of mitotic cells within the crypt by 60 % (P = 0·001) compared with placebo. This effect was limited to older participants (aged ≥50 years). No other differences were observed for the treatments with PD or RS as compared with their respective controls. PD did not influence any of the measured variables. RS, however, increased cell proliferation in the crypts of the macroscopically-normal rectum of older adults. Our findings suggest that the effects of RS on CCPS are not only dose, type of RS and health status-specific but are also influenced by age.

Alterations in the composition and metabolic activity of the gut microbiota appear to contribute to the development of obesity and associated metabolic diseases. However, the extent of this relationship remains unknown. Modulating the gut microbiota with non-digestible carbohydrates (NDC) may exert anti-obesogenic effects through various metabolic pathways including changes to appetite regulation, glucose and lipid metabolism and inflammation. The NDC vary in physicochemical structure and this may govern their physical properties and fermentation by specific gut bacterial populations. Much research in this area has focused on established prebiotics, especially fructans (i.e. inulin and fructo-oligosaccharides); however, there is increasing interest in the metabolic effects of other NDC, such as resistant dextrin. Data presented in this review provide evidence from mechanistic and intervention studies that certain fermentable NDC, including resistant dextrin, are able to modulate the gut microbiota and may alter metabolic process associated with obesity, including appetite regulation, energy and lipid metabolism and inflammation. To confirm these effects and elucidate the responsible mechanisms, further well-controlled human intervention studies are required to investigate the impact of NDC on the composition and function of the gut microbiota and at the same time determine concomitant effects on host metabolism and physiology.

Epidemiological and experimental evidence suggests that non-digestible carbohydrates (NDC) including resistant starch are protective against colorectal cancer. These anti-neoplastic effects are presumed to result from the production of the SCFA, butyrate, by colonic fermentation, which binds to the G-protein-coupled receptor GPR43 to regulate inflammation and other cancer-related processes. The WNT pathway is central to the maintenance of homeostasis within the large bowel through regulation of processes such as cell proliferation and migration and is frequently aberrantly hyperactivated in colorectal cancers. Abnormal WNT signalling can lead to irregular crypt cell proliferation that favours a hyperproliferative state. Butyrate has been shown to modulate the WNT pathway positively, affecting functional outcomes such as apoptosis and proliferation. Butyrate's ability to regulate gene expression results from epigenetic mechanisms, including its role as a histone deacetylase inhibitor and through modulating DNA methylation and the expression of microRNA. We conclude that genetic and epigenetic modulation of the WNT signalling pathway may be an important mechanism through which butyrate from fermentation of resistant starch and other NDC exert their chemoprotective effects.

Dietary non-digestible carbohydrates reduce the development of cows' milk allergy in mice. In the present study, the contribution of CD25+ regulatory T-cells (Treg) was investigated using in vivo Treg depletion and adoptive transfer studies. Mice were orally sensitised with casein and fed a diet containing 2 % short-chain galacto-, long-chain fructo- and acidic oligosaccharides (GFA) or a control diet. Donor splenocytes of mice sensitised with casein and fed the GFA or control diet were adoptively transferred to naive recipient mice, which were casein- or sham-sensitised and fed the control diet. In addition, in vivo or ex vivo CD25+ Treg depletion was performed using anti-CD25 (PC61). The acute allergic skin response upon intradermal casein challenge and casein-specific Ig were determined. Furthermore, T-helper (TH) 1 and TH2 cell numbers were analysed in the mesenteric lymph nodes. The oligosaccharide diet strongly reduced the development of the acute allergic skin response, which was abrogated by the in vivo anti-CD25 treatment. The diet enhanced the percentage of TH1 cells and tended to reduce the percentage of TH2 cells in casein-sensitised mice. Recipient mice were protected against the development of an acute allergic skin response when transferred with splenocytes from casein-sensitised GFA-fed donor mice before sensitisation. Ex vivo depletion of CD25+ Treg abrogated this transfer of tolerance. Splenocytes from sham-sensitised GFA-fed donor mice did not suppress the allergic response in recipient mice. In conclusion, CD25+ Treg contribute to the suppression of the allergic effector response in casein-sensitised mice induced by dietary intervention with non-digestible carbohydrates.

The present experiment aimed to study the influence of six sources of non-digestible carbohydrates (NDC) on the mucous layer in the colon of rats. The NDC sources used were as follows: cellulose (C); pectin (P); inulin; resistant starch (RS); barley hulls. The diets contained 108–140 g NDC/kg DM. A fibre-free (FF) diet served as a control. The diets were fed to forty-eight rats for 34–41 d. The thickness of the total mucous layer in the colon was increased (P < 0·05) in rats fed C, P and RS when compared with rats fed a FF diet. In the colon, positive correlations were observed between the total thickness of the mucous layer and the area of neutral mucins, the pool of SCFA and the pool of acetic acid, while it was negatively correlated with the proportion of butyrate. The total thickness of the mucous layer was not correlated with the MUC gene transcription. The transcription of the gene MUC2 was negatively correlated (P = 0·04), whereas the transcription of MUC3 was positively correlated (P = 0·05) with the butyrate pool in the caecum. No correlations between the MUC2 or MUC3 transcription and SCFA were found in the colon. Hence, the regulation of the MUC genes differs between the compartments of the hindgut and, within compartments, the MUC genes may be regulated differently. In conclusion, a diet providing a large pool of SCFA with a low proportion of butyrate in the colon stimulates the formation of a thick mucous layer, which probably benefits intestinal health.

Dietary non-digestible carbohydrates (NDC) play an important role in large-bowel health and one form of NDC, resistant starch (RS), can promote low levels of DNA damage and other markers of colonic health. The objective of the present study was to determine whether the ability of dietary RS or other NDC to influence colonic health, particularly DNA damage, is dependent on the type of dietary oil. We compared the effects of diets containing 10 % of NDC from cellulose, wheat bran, high-amylose maize starch (HAS, a rich source of RS type 2) or a retrograded HAS (RHAS, a rich source of RS type 3) on DNA damage, SCFA production and bacterial changes in the large bowel of rats. Each carbohydrate source was combined with 10 % fish oil (FO) or Sunola™ oil (SO; rich in oleic acid). There was a significant interaction between NDC and oil treatments on single-strand DNA breaks in colonocytes isolated from the colon. The damage in rats consuming RHAS was greater for FO consumption than for SO consumption. There was a significant interaction between NDC and oils on caecum weights and treatment effects of NDC and oils were observed for the weights and lengths of other gut tissues. Significant differences were found in colonic SCFA pools and caecal numbers of lactobacilli, bifidobacteria, Escherichia coli and Bacteroides fragilis with the various NDC and oil treatments. The present results demonstrate that the effects of NDC and oils, particularly on colonic DNA damage, can depend on how they are combined within the diet.