The purpose of the present study was to establish the prebiotic effect of a new xylo-oligosaccharide (XOS) and of an inulin-and-XOS mixture (INU -XOS) and to determine their effect on endotoxaemia (lipopolysaccharides (LPS)) and immune parameters. In this randomised, parallel, placebo-controlled, double-blind study, sixty healthy volunteers were randomly assigned to three groups, receiving either 5 g XOS, INU-XOS (3 g inulin þ 1 g XOS) or an equivalent weight of wheat maltodextrin (placebo) during 4 weeks. Faecal samples were collected to assess the effects of these products on microbiota, as well as SCFA composition, enzymatic activities and secretory IgA production. Circulating LPS was measured in plasma samples, and whole blood was incubated with LPS to measure cytokine expression. Consumption of XOS alone increased the faecal concentrations of Bifidobacterium and butyrate and activities of a-glucosidase and b-glucuronidase, while decreasing the concentrations of acetate and p-cresol. Consumption of XOS in combination with inulin did not decrease the concentrations of acetate and p-cresol, but increased in addition the faecal concentrations of total SCFA and propionate. Furthermore, consumption of XOS in combination with inulin decreased LPS concentrations in blood and attenuated LPS-induced increases in gene expression in IL-1b and LPS-induced decreases in gene expression in IL-13 in blood. In conclusion, consumption of XOS alone or in combination with inulin results in beneficial albeit different changes in the intestinal microbiome on a high-fat diet. In addition, consumption of XOS in combination with inulin attenuates the proinflammatory effects of a high-fat diet in the blood of healthy subjects.Key words: Xylo-oligosaccharides: Immunonutrition: Prebiotics: Lipopolysaccharides: CytokinesThe complex role of the human intestinal microbiota is emerging and its functions are now more and more established when considering energy metabolism, nutrient digestion, vitamin synthesis, epithelial defences and immune responses (1) . The composition and function of the humanassociated microbiota are considered as a partner of the host in order to fight infection and to improve inflammatory processes and conditions. There is an increasing body of evidence linking the physiopathology of metabolic diseases such as obesity or inflammatory bowel disease and the gut microbiota (2) .Through resistance to digestion in the upper gastrointestinal tract, non-digestible carbohydrates reach the colon intact to undergo a complete or partial fermentation in the large intestine. If they selectively stimulate the growth and/or the activity of the beneficial, health-promoting members of the gut microbiota, they meet the criteria of prebiotics (3 -6) . b(2 ! 1)-Fructans, which include inulin and fructo-oligosaccharides (FOS), are considered to be prebiotics, while xylo-oligosaccharides (XOS) are considered as candidate prebiotics (7) .Mice fed a high-fat diet exhibited a significant increase in plasma lipopolysaccharides (LPS)...

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Increasing evidence indicates that chlorpyrifos (CPF), an organophosphorus insecticide, is involved in metabolic disorders. We assess the hypothesis whether supplementation with prebiotics from gestation to adulthood, through a modulation of microbiota composition and fermentative activity, alleviates CPF induced metabolic disorders of 60 days old offspring. 5 groups of Wistar rats, from gestation until weaning, received two doses of CPF pesticide: 1 mg/kg/day (CPF1) or 3.5 mg/kg/day (CPF3.5) with free access to inulin (10g/L in drinking water). Then male pups received the same treatment as dams. Metabolic profile, leptin sensitivity, insulin receptor (IR) expression in liver, gut microbiota composition and short chain fatty acid composition (SCFAs) in the colon, were analyzed at postnatal day 60 in the offspring (PND 60). CPF3.5 increased offspring’s birth body weight (BW) but decreased BW at PND60. Inulin supplementation restored the BW at PND 60 to control levels. Hyperinsulinemia and decrease in insulin receptor β in liver were seen in CPF1 exposed rats. In contrast, hyperglycemia and decrease in insulin level were found in CPF3.5 rats. Inulin restored the levels of some metabolic parameters in CPF groups to ranges comparable with the controls. The total bacterial population, short chain fatty acid (SCFA) production and butyrate levels were enhanced in CPF groups receiving inulin. Our data indicate that developmental exposure to CPF interferes with metabolism with dose related effects evident at adulthood. By modulating microbiota population and fermentative activity, inulin corrected adult metabolic disorders of rats exposed to CPF during development. Prebiotics supply may be thus considered as a novel nutritional strategy to counteract insulin resistance and diabetes induced by a continuous pesticide exposure.

The presence of pesticide residues in food is a public health problem. Exposure to these substances in daily life could have serious effects on the intestine—the first organ to come into contact with food contaminants. The present study investigated the impact of a low dose (1 mg/day in oil) of the pesticide chlorpyrifos (CPF) on the community structure, diversity and metabolic response of the human gut microbiota using the SHIME® model (six reactors, representing the different parts of the gastrointestinal tract). The last three reactors (representing the colon) were inoculated with a mixture of feces from human adults. Three time points were studied: immediately before the first dose of CPF, and then after 15 and 30 days of CPF-oil administration. By using conventional bacterial culture and molecular biology methods, we showed that CPF in oil can affect the gut microbiota. It had the greatest effects on counts of culturable bacteria (with an increase in Enterobacteria, Bacteroides spp. and clostridia counts, and a decrease in bifidobacterial counts) and fermentative activity, which were colon-segment-dependent. Our results suggest that: (i) CPF in oil treatment affects the gut microbiota (although there was some discordance between the culture-dependent and culture-independent analyses); (ii) the changes are “SHIME®-compartment” specific; and (iii) the changes are associated with minor alterations in the production of short-chain fatty acids and lactate.

Dietary exposure to the organophosphorothionate pesticide chlorpyrifos (CPF) has been linked to dysbiosis of the gut microbiota. We therefore sought to investigate whether (i) CPF's impact extends to the intestinal barrier and (ii) the prebiotic inulin could prevent such an effect. In vitro models mimicking the intestinal environment (the SHIME®) and the intestinal mucosa (Caco-2/TC7 cells) were exposed to CPF. After the SHIME® had been exposed to CPF and/or inulin, we assessed the system's bacterial and metabolic profiles. Extracts from the SHIME®'s colon reactors were then transferred to Caco-2/TC7 cultures, and epithelial barrier integrity and function were assessed. We found that inulin co-treatment partially reversed CPF-induced dysbiosis and increased short-chain fatty acid production in the SHIME®. Furthermore, co-treatment impacted tight junction gene expression and inhibited pro-inflammatory signaling in the Caco-2/TC7 intestinal cell line. Whereas, an isolated in vitro assessment of CPF and inulin effects provides useful information on the mechanism of dysbiosis, combining two in vitro models increases the in vivo relevance.

High temperatures (HTs) during grain fi lling adversely impact grain yield and its end-use quality for wheat. HTs strongly reduce the expression of major enzymes associated with starch synthesis, whereas enzymes associated with defence against stress and protein folding are dramatically increased. Using proteomics tools, the effect of different temperature regimes on storage protein (SP) accumulation was investigated. HT signifi cantly decreased the quantity per grain of individual gliadin and glutenin spots, but at maturity the ratio of gliadin to glutenin was not modifi ed. HT during grain fi lling strongly reduced starch accumulation, modifi ed the size distribution of starch granules, and to a much lesser extent, reduced the quantity of total proteins per grain. The aggregation and polymerisation of SP was investigated using asymmetric fl ow fi eld fl ow fractionation. Previous analyses of near-isogenic hard/soft lines showed that characteristics of glutenin polymers were signifi cantly infl uenced by puroindoline alleles ( Pina-D1a and -D1b ), and proteomics analysis showed that a typical mechanism of unfolded protein response occurs in ER, resulting from stress during protein accumulation. Effects of alleles encoding puroindolines, HMW-GS and LMW-GS, and temperature during grain development on glutenin polymer characteristics, dough rheological properties, and bread loaf volume were investigated for 40 cultivars grown in six environments in France. A difference of only 2 °C in average daily air temperature between locations during the grain-fi lling period resulted in increased molecular mass of the glutenin