The mucus layer covering the gastrointestinal mucosa is considered the first line of defense against aggressions arising from the luminal content. It is mainly composed of high molecular weight glycoproteins called mucins. Butyrate, a shortchain fatty acid produced during carbohydrate fermentation, has been shown to increase mucin secretion. The aim of this study was to test 1) whether butyrate regulates the expression of various MUC genes, which are coding for protein backbones of mucins, and 2) whether this effect depends on butyrate status as the major energy source of colonocytes. Butyrate was provided at the apical side of human polarized colonic goblet cell line HT29-Cl.16E in glucose-rich or glucose-deprived medium. In glucose-rich medium, butyrate significantly increased MUC3 and MUC5B expression (1.6-fold basal level for both genes), tended to decrease MUC5AC expression, and had no effect on MUC2 expression. In glucose-deprived medium, i.e., when butyrate was the only energy source available, MUC3 and MUC5B increase persisted, whereas MUC5AC expression was significantly enhanced (3.7-fold basal level) and MUC2 expression was strikingly increased (23-fold basal level). Together, our findings show that butyrate is able to upregulate colonic mucins at the transcriptional level and even better when it is the major energy source of the cells. Thus the metabolism of butyrate in colonocytes is closely linked to some of its gene-regulating effects. The distinct effects of butyrate according to the different MUC genes could influence the composition and properties of the mucus gel and thus its protective function. mucin; short-chain fatty acids; energy source; human colonic cell line THE MUCUS LAYER, COVERING the gastrointestinal mucosa, is considered the first line of defense against mechanical, chemical, or microbiological aggressions arising from the luminal contents (14). Mucus is mostly composed of mucins, i.e., glycoproteins of high molecular weight, whose protein backbones are encoded by MUC genes. So far, at least 15 different MUC genes have been identified in humans (15,32). In the large intestinal mucosa, the main MUC genes are MUC2, and to a lesser extent MUC1, MUC3, and MUC4. MUC2 codes for the main secreted mucin in the colon, whereas MUC1, MUC3, and MUC4 mainly code for membrane-located mucins but also present splicing variants coding for secreted mucins (50). Apart from their gel-forming protective function, some membrane-linked mucins, such as MUC1 (22) and MUC4 (12), exhibit specific functions in adhesion and cell signaling.MUC gene expression is altered in many colonic diseases. MUC2 is overexpressed in mucinous colorectal carcinoma, whereas its expression is particularly low in nonmucinous carcinoma (17, 43). MUC5AC and MUC6 expressions are abnormally induced in colon adenoma (6, 9). Aberrant expression of MUC genes (8) as well as modifications of their transcription (34, 45) have also been observed in inflammatory bowel disease. In addition, the thickness of the mucus layer is reduced in ulce...

Increasing health issues related to immune and gut function such as inflammatory disorders, resistance to infections and metabolic syndrome demand modern analytical approaches to accelerate nutritional research aimed at health promotion and disease prevention. Gut microbial-human mutualism endows the host 'superorganism' with a fitness advantage including nutritional, immune and intestinal health aspects. The gut microbiome enlarges our genome and enhances our metabolic potential. Dietary modulation can significantly alter the microbiota community and metabolic activity, and consequently impacts on nutrient bioavailability and host metabolism. Although in an early stage, microbial metabolites generated during colonic fermentation of food stuffs may have beneficial or deleterious effects on intestinal health and immunity, as summarized in this review. However, current evidence is largely based on in vitro and animal studies while substantiation in humans is lacking. The challenge to establish coherent links between the bioconversion of non-digestible food ingredients, their bioavailability and their downstream effects on the host metabolism may be achieved by metabolomics. In this review, metabolomics studies focusing on microbe-host mutualism have demonstrated that metabolomics is capable of detecting and tracking diverse microbial metabolites from different non-digestible food ingredients, of discriminating between phenotypes with different inherent microbiota and of potentially diagnosing infection and gastrointestinal diseases. Integrative approaches such as the combined analysis of the metabolome in different biofluids together with other -omics technologies will cover exogenous and endogenous effects and hence show promise to generate novel hypotheses for innovative functional foods impacting gut health and immunity.

In the developing world major public health issues such as malnutrition and compromised physical development are intimately linked to altered gut morphology and function with underlying chronic inflammatory responses. In these societies the downward spiral of malnutrition and infections does not seem to be remedied by well-informed nutritional interventions that supplement the identified nutrient deficiencies, suggesting that additional strategies are needed. The aim of this scientific opinion paper is to consider how a child from the developing world might benefit, separately and additively, from interventions targeted to impact hygiene, nutritional status, disease resistance and gut function, if successful interventions could be found. A failure to tackle environmental enteropathy (EE) may be a critical limiting factor that can explain the relative lack of success of interventions focussed on micronutrient supplementation so far. Therefore this paper starts with a summary of the aetiology and consequences of EE on child health and the current recommendations aimed at tackling this problem. Then a number of hypotheses will be considered in terms of research strategy to positively affect nutritional status, intestinal health and growth of children with EE, with the aim of inspiring future innovative strategies, for both the food industry and the public health sector, which could benefit millions of children.

The mucus layer covering the epithelium is one of the main lines of defense of the colonic barrier. Both mucus gel and mucin expressions are altered during colonic inflammation and could be involved in epithelial repair. We postulated that modulating colonic mucus and mucins by probiotic supplementation could contribute to healing inflammatory mucosa. Our aim in this study was to determine whether probiotics could repair dextran-sodium sulfate (DSS)-induced chronic colitis in mice, and whether modifications of the colonic mucins could be involved. For that purpose, the VSL#3 probiotic mixture of 8 lactic acid bacteria probiotic strains was administered daily for 2 wk to mice with a mucosa impaired by a mild DSS treatment, and to mice with a normal mucosa. Probiotic strains survived in the gastrointestinal tract, increased the cecal concentrations of bifidobacteria, and modified cecal microflora metabolic activity in both DSS-treated and healthy mice. However, probiotic supplementation did not reverse the inflammation induced by DSS at either the macroscopic or histological level. Concurrently, probiotics did not modify the colonic mucus barrier, in terms of either mucin gene expression or adherent mucus layer thickness. In conclusion, the modification of microflora by supplementation with the VSL#3 probiotic mixture did not help to repair the colonic barrier breakdown caused by DSS treatment. The potential healing roles of mucins were neither confirmed nor invalidated by this study.

The present study aimed to determine the prebiotic effect of fruit and vegetable shots containing inulin derived from Jerusalem artichoke (JA). A three-arm parallel, placebo-controlled, double-blind study was carried out with sixty-six healthy human volunteers (thirty-three men and thirty-three women, age range: 18-50 years). Subjects were randomised into three groups (n 22) assigned to consume either the test shots, pear-carrot-sea buckthorn (PCS) or plum-pear-beetroot (PPB), containing JA inulin (5 g/d) or the placebo. Fluorescent in situ hybridisation was used to monitor populations of total bacteria, bacteroides, bifidobacteria, Clostridium perfringens/histolyticum subgroup, Eubacterium rectale/ Clostridium coccoides group, Lactobacillus/Enterococcus spp., Atopobium spp., Faecalibacterium prausnitzii and propionibacteria. Bifidobacteria levels were significantly higher on consumption of both the PCS and PPB shots (10·0 (SD 0·24) and 9·8 (SD 0·22) log 10 cells/g faeces, respectively) compared with placebo (9·3 (SD 0·42) log 10 cells/g faeces) (P, 0·0001). A small though significant increase in Lactobacillus/Enterococcus group was also observed for both the PCS and PPB shots (8·3 (SD 0·49) and 8·3 (SD 0·36) log 10 cells/g faeces, respectively) compared with placebo (8·1 (SD 0·37) log 10 cells/g faeces) (P¼ 0·042). Other bacterial groups and faecal SCFA concentrations remained unaffected. No extremities were seen in the adverse events, medication or bowel habits. A slight significant increase in flatulence was reported in the subjects consuming the PCS and PPB shots compared with placebo, but overall flatulence levels remained mild. A very high level of compliance (. 90 %) to the product was observed. The present study confirms the prebiotic efficacy of fruit and vegetable shots containing JA inulin.

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Colonic mucosal protection is provided by mucous gel, mainly composed of secreted (Muc2) and membrane-bound (Muc1, Muc3, Muc4) mucins. Our aim was to determine the expression profile of secreted and membrane-bound mucins in experimental dextran sulfate sodium (DSS)-induced colitis. Acute colitis was induced in Balb/C mice by oral administration of 1.0% DSS (5 days) and chronic colitis was maintained by subsequent 0.15% DSS treatment (28 days). Clinical symptoms (mortality, weight gain), stool scores, and MPO activity confirmed the inflammatory state in the two phases of colitis. Muc2 gene expression was not modified by colitis, whereas Muc3 gene expression was increased (x2) only in the cecum and the distal colon of mice after acute colitis. Muc1 and Muc4 mRNA levels were more significantly increased in the cecum (x8-10) than in colonic segments (x4) after acute colitis. TFF3 involved in mucosal repair was up-regulated during colitis induction. These results indicate that Muc and TFF3 genes are regulated early in inflammation and suggest that their mRNA levels could be used as early markers of inflammation.

Colonic mucosal protection is provided by the mucus gel, mainly composed of mucins. Several factors can modulate the formation and the secretion of mucins, and among them butyrate, an endproduct of carbohydrate fermentation. However, the specific effect of butyrate on the various colonic mucins, and the consequences in terms of the mucus layer thickness are not known. Our aim was to determine whether butyrate modulates colonic MUC genes expression in vivo and whether this results in changes in mucus synthesis and mucus layer thickness. Mice received daily for 7 days rectal enemas of butyrate (100 mM) versus saline. We demonstrated that butyrate stimulated the gene expression of both secreted (Muc2) and membrane-linked (Muc1, Muc3, Muc4) mucins. Butyrate especially induced a 6-fold increase in Muc2 gene expression in proximal colon. However, butyrate enemas did not modify the number of epithelial cells containing the protein Muc2, and caused a 2-fold decrease in the thickness of adherent mucus layer. Further studies should help understanding whether this last phenomenon, i.e. the decrease in adherent mucus gel thickness, results in a diminished protective function or not.