The incidence of obesity related glomerulopathy (ORG) is rising worldwide with very limited treatment methods. Paralleled with the gut-kidney axis theory, beneficial effects of butyrate, one of short-chain fatty acids produced by gut microbiota, on metabolism and certain kidney diseases have gained growing attention. However, the effects of butyrate on ORG and its underlying mechanism are largely unexplored. In this study, a mice model of ORG was established with high-fat diet (HFD) feeding for 16 weeks, and sodium butyrate treatment was initiated at the 8th week. Podocytes injury, oxidative stress, and mitochondria function were evaluated in mice kidney and validated in vitro in palmitic acid (PA) treated-MPC5 cells. Further, the molecular mechanisms of butyrate on podocytes were explored. Compared with controls, sodium butyrate treatment alleviated kidney injuries and renal oxidative stress in HFD-fed mice. In MPC5 cells, butyrate ameliorated PA-induced podocyte damage and helped maintain the structure and function of the mitochondria. Moreover, the effects of butyrate on podocytes were mediated via GPR43-Sirt3 signal pathway, as evidenced by the diminished effects of butyrate with the intervention of GPR43 or Sirt3 inhibitors. In summary, we conclude that butyrate has therapeutic potential for the treatment of ORG. It attenuates HFD-induced ORG and podocytes injuries through the activation of GPR43-Sirt3 signaling pathway.

A majority of Australians consume a limited range of different dietary fibres and insufficient total dietary fibre(1). This contributes to low intestinal microbial diversity and impaired microbial function, such as capability in producing beneficial metabolites like short-chain fatty acids (SCFA). This diet-induced dysbiosis is associated with poor gastrointestinal health and a broad range of non-communicable diseases(2). Our study aimed to determine whether one dietary change, substitution of white bread with a high fibre bread improves faecal microbial diversity and butyrate-producing capability. Twenty-six healthy adults completed a randomised, cross-over, single-blinded intervention. Over the two intervention phases separated with a 4-wk washout, participants consumed either 3 slices of a high fibre bread (Prebiotic Cape Seed Loaf with BARLEYmax®) or control white bread as part of the usual diet, each for 2 weeks. At the beginning and end of each intervention period, participants completed a 24-h diet recall, a gut symptoms rating questionnaire and provided a faecal sample for microbiome analysis. The composition of faecal microbiome was characterised using 16S rRNA amplicon sequencing (V3-V4) and a marker of butyrate synthesis capability, the faecal content of butyryl-CoA:acetate CoA-transferase (BCoAT) gene was assessed using Real-time PCR. The high fibre bread intervention increased the servings of whole grain from 1.5 to 4 per day and increased total dietary fibre intake to 40 g/d which was double the amount of fibre consumed by participants at baseline or during the white bread intervention. Compared to white bread, the high fibre bread increased richness and evenness (Shannon, p = 0.014) of the gut microbiota and increased the relative abundance of SCFA producing taxa Lachnospiracae ND3007 group (p <0.001, FDR = 0.019). In addition, the high-fibre bread tended to increase relative abundance of butyrate-producing genus Roseburia, and microbial BCoAT gene content compared to white bread. In conclusion, the substitution of white bread with high-fibre bread improved the diversity of gut microbiota, specific microbes involved in SCFA production and may enhance the butyrate production capability of gut microbiota in healthy adults.

Macauba (Acrocomia aculeata) is a palm tree native from Brazil, whose pulp is rich in oil that has a high content of oleic acid and carotenoids. Macauba pulp oil can bring health benefits due to its bioactive compounds; however, its effects on gut health are unknown. Thus, the objective of this study was to evaluate the effect of macauba pulp oil on the intestinal health in mice fed a high-fat (HF) diet. Male C57BL1/6 mice were randomly divided into three groups (10 animals/group): control diet, HF diet and HF diet with 4 % of macauba pulp oil (HFM). Concentration of short-chain fatty acids (SCFA), faecal pH and histomorphometric analysis of the colon were performed. Content of colon samples was used on microbiome analysis using 16S rRNA amplicon sequencing. Animals from the HFM group had higher butyric acid content and goblet cells number, greater circular and longitudinal muscle layer and higher α-diversity compared with the HF group. Moreover, consumption of MPO reduced Desulfobacterota phylum, Ruminococcaceae, Oscillospiraceae, Prevotellaceae, Bifidobacteriaceae family, Faecalibacterium, Prevotella, Ruminococcus and Enterorhabdus genus. Therefore, macauba pulp oil was able to modulate the gut microbiota and enhance intestinal barrier morphology, showing preventive effects on gut dysbiosis in mice fed a HF diet.

Metabolites produced by microbial fermentation in the human intestine, especially short-chain fatty acids (SCFAs), are known to play important roles in colonic and systemic health. Our aim here was to advance our understanding of how and why their concentrations and proportions vary between individuals. We have analysed faecal concentrations of microbial fermentation acids from 10 human volunteer studies, involving 163 subjects, conducted at the Rowett Institute, Aberdeen, UK over a 7-year period. In baseline samples, the % butyrate was significantly higher, whilst % iso-butyrate and % iso-valerate were significantly lower, with increasing total SCFA concentration. The decreasing proportions of iso-butyrate and iso-valerate, derived from amino acid fermentation, suggest that fibre intake was mainly responsible for increased SCFA concentrations. We propose that the increase in % butyrate among faecal SCFA is largely driven by a decrease in colonic pH resulting from higher SCFA concentrations. Consistent with this, both total SCFA and % butyrate increased significantly with decreasing pH across five studies for which faecal pH measurements were available. Colonic pH influences butyrate production through altering the stoichiometry of butyrate formation by butyrate-producing species, resulting in increased acetate uptake and butyrate formation, and facilitating increased relative abundance of butyrate-producing species (notably Roseburia and Eubacterium rectale).

This study aimed to investigate the relationships between diet quality, the relative abundance of butyrate-producing bacteria of the gut microbiome and muscle mass, strength and function. In this cross-sectional study, n = 490 men (64.4 ± 13.5 years) from the Geelong Osteoporosis Study provided food frequency questionnaire data, from which the Australian Recommended Food Score (ARFS) and Dietary Inflammatory Index (DII) score were calculated. Muscle mass (skeletal muscle index from DXA-derived lean mass), muscle strength (handgrip strength) and muscle function (Timed Up-and-Go test) were measured. Participants provided stool samples for 16S rRNA gene sequencing. There was no evidence of associations between alpha or beta diversity and muscle health measures. A healthier ARFS score was positively associated with the relative abundance of butyrate-producing bacteria (β 0.09, 95%CI 0.03, 0.15) and a higher (pro-inflammatory) DII score was associated with lower relative abundance of butyrate-producing bacteria (β −0.60, 95%CI −1.06, −0.15). The relative abundance of butyrate-producing bacteria was positively associated with healthier muscle mass, strength and function; however, these relationships were attenuated in multivariable models. These findings support the role of diet quality in achieving a healthier gut microbiome, however, further evidence is required for a gut-muscle axis in humans.

The health benefits of fruit, vegetables and dietary fibre have been promoted for many years. Much of the supporting evidence is circumstantial or even contradictory and mechanisms underlying health benefits of specific foods are poorly understood. Colorectal cancer shows marked geographical differences in incidence, probably linked with diet, and explanations for this require knowledge of the complex interactions between diet, microbiota and the gut epithelium. Dietary fibres can act as prebiotics, encouraging growth of saccharolytic bacteria, but other mechanisms are also important. Some but not all soluble fibres have a ‘contrabiotic’ effect inhibiting bacterial adherence to the epithelium. This is particularly a property of pectins (galacturonans) whereas dietary fructans, previously regarded as beneficial prebiotics, can have a proinflammatory effect mediated via toxic effects of high butyrate concentrations. This also suggests that ulcerative colitis could in part result from potentially toxic faecal butyrate concentrations in the presence of a damaged mucus layer. Epithelial adherence of lectins, either dietary lectins as found in legumes, or bacterial lectins such as the galactose-binding lectin expressed by colon cancer-associated Fusobacterium nucleatum, may also be important and could be inhibitable by specific dietary glycans. Conversely, emulsifiers in processed foods may increase bacterial translocation and alter the microbiota thus promoting inflammation or cancer. Focusing on one condition is of limited value although in developing public health messages and growing evidence for impacts of dietary components on all-cause mortality is gaining more attention. We are only just starting to understand the complex interactions between food, the microbiota and health.

The importance of the use of exogenous butyrate in calves’ diets is due to its role as a factor stimulating the functional development of ruminal epithelium and improving calf performance during the transition from preruminant to ruminant status. Our review will first present results related to effects of the administration of butyrate in calves’ diets on the development of ruminal epithelium toward a more effective absorption and metabolism of fermentation products from the rumen. The introduction of sodium butyrate at a level of about 0.3% of diet dry matter is accompanied by an increase to 35% in butyrate concentration in the rumen of 33-day-old calves. Mutual reliance between an enhanced ruminal concentration of butyrate and the activities of transcription factors, genes and proteins involved in cell proliferation, ketogenesis and the maintenance of cell pH homeostasis in the ruminal epithelial cells has been clearly confirmed in many experiments. Second, the review presents results related to the effects of the introduction of butyrate salts in the diet on calf performance. Of 11 studies a positive effect was found in six; five of these were obtained from the calves that started receiving butyrate supplement at a level of about 0.3% diet dry matter from the age of 3 to 5 days. Results indicate that when a supplement is given to calves soon after birth the functional development of ruminal epithelium in cooperation with the endocrine and digestion systems is transferred into improving the efficiency of rearing. There have been no studies on the effects of greater amounts of butyrate salts in milk replacer; butyrate constitutes about 1.2% of the whole cow’s milk dry matter. In older calves, when butyrate administration is provided as a component of a starter concentrate at the increasing inclusion rate from 0.3% to 3.0%, the practical effect in calf performance relates to the risk of depression of rumen pH below 5.5 and accompanying disruption of the organization of the ruminal epithelial tissue. The higher risk is noted in calves received starter with substantial content of a rapidly degradable starch. At present, the insufficient number of positive results confirming the beneficial effect of butyrate supplements in terms of an improvement in performance does not allow their recommendation for use in the practical feeding of calves.

In the field of animal nutrition, butyrate is used as a zootechnical ingredient and can be used as an unprotected salt or in the form of protected derivatives such as butyrate glycerides or butyrate-loaded matrices. Dietary butyrate supplementation has been shown to improve growth performance and resilience of broiler chickens through distinct mechanisms, operating on both eukaryotic and prokaryotic cells. Firstly, butyrate influences endogenous avian cells in multiple ways: it is an agonist of free-fatty acid receptors, an inhibitor of pro-inflammatory pathways, an epigenetic modulating agent and acts as an energy source. Secondly, butyrate influences the microbiota residing in the avian gastrointestinal tract (GIT) as a result of its bacteriostatic properties. The responses, e.g. changes in growth performance, gut morphology, carcass traits or nutrient digestibility of chickens, to dietary butyrate supplementation are inconsistent with factors such as additive inclusion level, diet composition, age and health status of the bird modulating the effects of butyrate and its derivatives. For many derivatives, the precise GIT segment wherein butyrate is released is unclear. Release location may affect the observed responses to butyrate given the diversity of cell types and pH conditions encountered throughout the gastrointestinal tract of poultry, and the differences in microbiota composition in the different gut segments. As a consequence, our understanding of the mode of action of butyrate is hampered. Characterisation of existing derivatives and development of targeted-release formulations are, therefore, important to gain insight in the different physiological effects butyrate can elicit in broiler chickens.

Epidemiological studies have identified increased colorectal cancer (CRC) risk with high red meat (HRM) intakes, whereas dietary fibre intake appears to be protective. In the present study, we examined whether a HRM diet increased rectal O6-methyl-2-deoxyguanosine (O6MeG) adduct levels in healthy human subjects, and whether butyrylated high-amylose maize starch (HAMSB) was protective. A group of twenty-three individuals consumed 300 g/d of cooked red meat without (HRM diet) or with 40 g/d of HAMSB (HRM+HAMSB diet) over 4-week periods separated by a 4-week washout in a randomised cross-over design. Stool and rectal biopsy samples were collected for biochemical, microbial and immunohistochemical analyses at baseline and at the end of each 4-week intervention period. The HRM diet increased rectal O6MeG adducts relative to its baseline by 21 % (P< 0·01), whereas the addition of HAMSB to the HRM diet prevented this increase. Epithelial proliferation increased with both the HRM (P< 0·001) and HRM+HAMSB (P< 0·05) diets when compared with their respective baseline levels, but was lower following the HRM+HAMSB diet compared with the HRM diet (P< 0·05). Relative to its baseline, the HRM+HAMSB diet increased the excretion of SCFA by over 20 % (P< 0·05) and increased the absolute abundances of the Clostridium coccoides group (P< 0·05), the Clostridiumleptum group (P< 0·05), Lactobacillus spp. (P< 0·01), Parabacteroides distasonis (P< 0·001) and Ruminococcus bromii (P< 0·05), but lowered Ruminococcus torques (P< 0·05) and the proportions of Ruminococcus gnavus, Ruminococcus torques and Escherichia coli (P< 0·01). HRM consumption could increase the risk of CRC through increased formation of colorectal epithelial O6MeG adducts. HAMSB consumption prevented red meat-induced adduct formation, which may be associated with increased stool SCFA levels and/or changes in the microbiota composition.

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.

The gut microbiota and its metabolic products interact with the host in many different ways, influencing gut homoeostasis and health outcomes. The species composition of the gut microbiota has been shown to respond to dietary change, determined by competition for substrates and by tolerance of gut conditions. Meanwhile, the metabolic outputs of the microbiota, such as SCFA, are influenced both by the supply of dietary components and via diet-mediated changes in microbiota composition. There has been significant progress in identifying the phylogenetic distribution of pathways responsible for formation of particular metabolites among human colonic bacteria, based on combining cultural microbiology and sequence-based approaches. Formation of butyrate and propionate from hexose sugars, for example, can be ascribed to different bacterial groups, although propionate can be formed via alternative pathways from deoxy-sugars and from lactate by a few species. Lactate, which is produced by many gut bacteria in pure culture, can also be utilised by certain Firmicutes to form butyrate, and its consumption may be important for maintaining a stable community. Predicting the impact of diet upon such a complex and interactive system as the human gut microbiota not only requires more information on the component groups involved but, increasingly, the integration of such information through modelling approaches.

The global prevalence of Fe deficiency is high and a common corrective strategy is oral Fe supplementation, which may affect the commensal gut microbiota and gastrointestinal health. The aim of the present study was to investigate the impact of different dietary Fe concentrations on the gut microbiota and gut health of rats inoculated with human faecal microbiota. Rats (8 weeks old, n 40) were divided into five (n 8 each) groups and fed diets differing only in Fe concentration during an Fe-depletion period (12 weeks) and an Fe-repletion period (4 weeks) as follows: (1) Fe-sufficient diet throughout the study period; (2) Fe-sufficient diet followed by 70 mg Fe/kg diet; (3) Fe-depleted diet throughout the study period; (4) Fe-depleted diet followed by 35 mg Fe/kg diet; (5) Fe-depleted diet followed by 70 mg Fe/kg diet. Faecal and caecal samples were analysed for gut microbiota composition (quantitative PCR and pyrosequencing) and bacterial metabolites (HPLC), and intestinal tissue samples were investigated histologically. Fe depletion did not significantly alter dominant populations of the gut microbiota and did not induce Fe-deficiency anaemia in the studied rats. Provision of the 35 mg Fe/kg diet after feeding an Fe-deficient diet significantly increased the abundance of dominant bacterial groups such as Bacteroides spp. and Clostridium cluster IV members compared with that of an Fe-deficient diet. Fe supplementation increased gut microbial butyrate concentration 6-fold compared with Fe depletion and did not affect histological colitis scores. The present results suggest that Fe supplementation enhances the concentration of beneficial gut microbiota metabolites and thus may contribute to gut health.

Fibre has been shown to exert a number of benefits on gastrointestinal (GI) health, yet its intake is low. Addition of novel fibres to food products may increase fibre intake and improve gut health. The objective of the present study was to evaluate the influence of three novel fibres on GI outcomes in healthy human subjects. A total of twenty healthy participants (ten men and ten women) with normal BMI (23 (sem 2) kg/m2) participated in the present randomised, double-blind, cross-over study with five treatment periods. Participants consumed a maltodextrin control or 20–25 g/d fibre from soluble maize fibre (SCF) or resistant starch (RS), alone or in combination with pullulan (SCF+P and RS+P). The treatment periods were 7 d with a 3-week washout between the periods. Stool samples were collected on day 7 of each period, and GI tolerance was assessed via a questionnaire on days 1 and 6. There were no treatment differences in stool weight or consistency. SCF significantly reduced stool pH and increased total SCFA production compared with RS and control. RS+P significantly increased the percentage of butyrate compared with all the other treatments. Overall, GI symptoms were minimal. SCF+P led to the highest GI score on day 1, while RS+P had the highest score on day 6. Both SCF treatments caused a significant shift in the gut microbial community. These functional fibres are generally well tolerated, have minimal effects on laxation and may lead to beneficial changes in SCFA production in healthy adults.

The present study was conducted to determine the effect of dietary supplementation of organic acids combined with synergistic components, using a commercial product Lumance™ (Innovad NV, Belgium) containing esterified butyrins, propionic acid and sorbic acid, with medium chain fatty acids (capric, caprylic, and lauric acid) and plant extracts, on the productive performance and mortality of growing broiler chickens. A total of 492, one day old broiler chicks (Ross 308) were randomly allocated to four experimental treatments either with an unsupplemented control or 0.05, 0.1 or 0.15% organic acid mixture in a pelleted corn/soyabean meal diet, which were offered ad libitum until 35 days of age. Results showed that birds in the 0.1% supplemented diet group gave significantly higher (P < 0.05) body weights during the first two weeks of age and increased weight gain during the first three weeks of age. The inclusion had no effect on broiler mortality.

Tributyrin (TBT) is a TAG composed of three butyric acids that has beneficial effects on ulcerative colitis due to its trophic, anti-inflammatory, pro-apoptotic and anti-carcinogenic properties. The goal of the present study was to evaluate the efficacy and mechanisms of action of TBT supplementation in the prevention of mucosal damage in experimental colitis. Mice received either a control diet or a TBT-supplemented diet for 15 d. Colitis was induced by dextran sodium sulphate administration during the last 7 d. Mucosal damage and the activation of immune cells and cytokines were determined by histological score, flow cytometry and ELISA. Leucocyte rolling and adhesion were assessed by intravital microscopy. Oxidative stress was determined by monitoring hydroperoxide concentration and evaluating superoxide dismutase (SOD) and catalase activities. Intestinal permeability was analysed using diethylenetriaminepentaacetate acid (99mTcDTPA). Compared with the colitis group, the animals in the colitis+TBT group had reduced mucosal damage and neutrophil and eosinophil mucosal infiltration, which were associated with a higher percentage of regulatory T cells (Treg) and higher levels of transforming growth factor β and IL-10 in the lamina propria. The level of in vivo leucocyte adhesion in the colon microvasculature was reduced after TBT supplementation. A lower level of hydroperoxide and higher levels of SOD and catalase activities were associated with TBT supplementation. TBT-supplemented mice showed reduced intestinal permeability to the levels intermediate between the control and colitis groups. In conclusion, the present results show that TBT has positive effects on colonic restructuring in experimental colitis. Additionally, TBT supplementation changes the immune response by controlling inflammation and regulating the expression of anti-inflammatory cytokines and Treg.

Colorectal cancer (CRC) is a leading cause of preventable cancer deaths worldwide, with dietary factors being recognised as key risk modifiers. Foods containing dietary fibre are protective to a degree that the World Cancer Research Fund classifies the evidence supporting their consumption as ‘convincing’. The mechanisms by which fibre components protect against CRC remain poorly understood, especially their interactions with the gut microbiome. Fibre is a composite of indigestible plant polysaccharides and it is emerging that fermentable fibres, including resistant starch (RS), are particularly important. RS fermentation induces SCFA production, in particular, relatively high butyrate levels, and in vitro studies have shown that this acid has strong anti-tumorigenic properties. Butyrate inhibits proliferation and induces apoptosis of CRC cell lines at physiological concentrations. These effects are attributed to butyrate's ability to alter gene transcription by inhibiting histone deacetylase activity. However, the more recent discovery of G-protein coupled receptors that bind butyrate and other SCFA and data obtained from proteomic and genomic experiments suggest that alternative pathways are involved. Here, we review the mechanisms involved in butyrate-induced apoptosis in CRC cells and, additionally, the potential role this SCFA may play in mediating key processes in tumorigenesis including genomic instability, inflammation and cell energy metabolism. This discussion may help to inform the development of strategies to lower CRC risk at the individual and population levels.

The effects of age on microbiota composition, gut fermentation end-product formation and peripheral lymphocyte numbers were compared between old and young adult Beagle dogs fed four kibble diets differing in yeast cell wall contents. The experiment had a double 4 × 4 Latin square design, one with four mature dogs (4 years old) and the other with four old dogs (10 years old), with four replicates (diets) per dog. In each period a 15 d adaptation period preceded a 5 d total collection of faeces for the digestibility trial. On day 21, fresh faecal samples were collected for the determination of bacterial enumeration, pH, biogenic amine and short-chain fatty acid. Flow cytometry was used for immunophenotypic evaluation. Dogs were fed four kibble diets with similar composition with 0, 0·15, 0·30 and 0·45 % of yeast cell wall (as-fed), respectively. Data were evaluated using general linear models of Statistical Analysis Systems statistical software (P < 0·05). No evidence of a difference in faecal bacteria counts between ages was found (total aerobes, total anaerobes, Bifidobacterium, Lactobacillus, Clostridium and Escherichia coli: P>0·15). Faecal concentrations of butyrate, histamine, agmatine and spermine were lower (P ≤ 0·05) and faecal pH was higher (P = 0·03) in older dogs than in mature adult dogs, suggesting an alteration in bacterial metabolic activity, or in the rate of intestinal absorption of these compounds. Concentrations of T-lymphocytes, T-cytotoxic lymphocytes and B-lymphocytes were also lower (P ≤ 0·01) in older dogs than in mature adult dogs. The study confirmed alterations in peripheral lymphocytes and revealed a reduced concentration of some fermentation end products in the colon of old dogs.

Epidemiological studies have suggested that dietary fibre lowers the risk of colorectal cancer, which may be due to increased butyrate production from colonic fermentation of a type of fibre, resistant starch (RS). The present study investigated the effects of dietary RS and butyrylated RS on the faecal microbiota of rats treated with azoxymethane. A total of four groups of nine rats were fed diets containing either standard maize starch (low-amylose maize starch (LAMS), low RS), LAMS with 3 % tributyrin (LAMST), cooked 10 % high-amylose maize starch (HAMS, high RS) or cooked 10 % butyrylated HAMS (HAMSB). Faecal samples were examined by denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S rRNA gene fragments. Multivariate analysis demonstrated no differences between faecal microbiota before treatment but revealed differences in DGGE patterns between diet groups, with the exception of the two low-RS groups (LAMS and LAMST). Subsequent analysis identified eleven DGGE bands contributing significantly to the differentiation between diets. These phylotypes belonged to Clostridiales (five), Lactobacillus (one) and Bacteroidetes (five) lineages. Rats fed HAMS had increased concentration of propionate in their distal colonic digesta and developed faecal populations containing Ruminococcus bromii-like bacteria. HAMSB increased propionate and butyrate concentrations in distal colonic digesta and was associated with the appearance of two non-butyrate-producing bacteria, Lactobacillus gasseri and Parabacteroides distasonis. In conclusion, supplementation with specific dietary RS leads to changes in faecal microbiota profiles that may be associated with improved bowel health.

There is strong epidemiological evidence that more physical activity is associated with reduced risk of colon cancer, but the amount or type of activity necessary to invoke this protection is disputed, and the mechanism that is responsible has not been elucidated. The present study compared the effects of two contrasting exercise regimens on intestinal tumourigenesis in Min mice, and investigated two novel mechanistic factors: colonic butyrate and sleep. From 5 weeks of age, Min mice were exercised by running on a treadmill (TR; ≤ 21 m/min, 30–60 min/d, 5 d/week, ≤ 12 weeks). Additional groups of mice were provided with an exercise wheel (WH) or no exercise (CON). Mice had free access to a Western-style, high-fat diet. WH mice ran 3·97 km (females) and 1·92 km (males) daily (P = 0·002). There were no differences in body weight gain or body composition between treatment groups. Treadmill running reduced the numbers of larger ( ≥ 2 mm diameter) tumours (P = 0·042), and tended to reduce tumour multiplicity in the colon (P = 0·049). TR mice had a higher molar proportion of butyrate in colonic digesta than CON mice (P = 0·030), and when treatment groups were combined, there was a weak negative correlation (r − 0·174, P = 0·061) between butyrate molar proportion and total tumour number. In a subset of animals in which non-exercise physical activity was monitored, there were strong positive correlations between sleep duration and both tumour multiplicity (P < 0·001) and tumour burden (P = 0·001). More studies of the effects of sleep and of colonic butyrate in mediating the effects of physical activity on intestinal tumourigenesis are warranted.

The purpose of this research was to test the hypothesis that starch-entrapped microspheres would produce favourable fermentation profiles and microbial shifts during in vitro fermentation with the faecal microbiota from patients with inflammatory bowel disease (IBD). In vitro fermentation was carried out using a validated, dynamic, computer-controlled model of the human colon (Toegepast Natuurwetenschappelijk Onderzoek gastro-intestinal model-2) after inoculation with pooled faeces from healthy individuals, patients with inactive IBD (Crohn's disease (CD)) or patients with active IBD (ulcerative colitis (UC)). Starch-entrapped microspheres fermented more slowly and produced more butyrate than fructo-oligosaccharides (FOS) when fermented with the faecal microbiota from patients with active UC. When fermented with the microbiota from patients with inactive CD, starch-entrapped microspheres also fermented more slowly but produced similar amounts of butyrate compared with FOS. Starch-entrapped microspheres showed a greater ability to maintain a low pH during simulated-distal colon conditions compared with FOS. After fermentation with the microbiota from inactive CD patients, starch-entrapped microspheres resulted in lower concentrations of some potentially harmful gut bacteria, included in Bacteroides, Enterococcus, Fusobacterium and Veillonella, compared with FOS. These findings suggest that slow fermenting starch-entrapped microspheres may induce a favourable colonic environment in patients with IBD through high butyrate production, maintenance of low pH in the distal colon and inhibition of the growth of potentially harmful bacteria.