Luminal contents from the gut of colicky infants induce visceral hypersensitivity in mice.

BACKGROUND: The pathophysiology of infantile colic is poorly understood, though various studies report gut microbiota dysbiosis in colicky infants. We aimed to test the hypothesis that colic-related dysbiosis is associated with visceral hypersensitivity triggered by an altered luminal milieu. METHODS: Fecal samples from seven colicky and seven non-colicky infants were studied. Fecal supernatants (FS) were infused into the colons of C57/Bl6 mice (n=10/specimen). Visceral sensitivity was subsequently assessed in the animals by recording their abdominal muscle response to colorectal distension (CRD) by electromyography (EMG). Serine and cysteine protease activities were assessed in FS with specific substrates. Infant fecal microbiota composition was analyzed by DNA extraction and 16S rRNA gene pyrosequencing. KEY RESULTS: FS from colicky infants triggered higher EMG activity than FS from non-colicky infants in response to both the largest CRD volumes and overall, as assessed by the area under the curve of the EMG across all CRD volumes. Infant crying time strongly correlated with mouse EMG activity. Microbiota richness and phylogenetic diversity were increased in the colicky group, without showing prominent microbial composition alterations. Only Bacteroides vulgatus and Bilophila wadsworthia were increased in the colicky group. Bacteroides vulgatus abundance positively correlated with visceral sensitivity. No differences were found in protease activities. CONCLUSIONS & INFERENCES: Luminal contents from colicky infants trigger visceral hypersensitivity, which may explain the excessive crying behavior of these infants. Additional studies are required to determine the nature of the compounds involved, their mechanism of action, and the potential implications of intestinal microbiota in their generation.

Effect of a mixture of bovine milk oligosaccharides, Lactobacillus rhamnosus NCC4007 and long-chain polyunsaturated fatty acids on catch-up growth of intra-uterine growth-restricted rats.

AIM: To investigate the effect of a nutritional mixture (bovine milk oligosaccharides, Lactobacillus rhamnosus NCC4007, arachidonic and docosahexaenoic acid) on growth of intrauterine growth-restricted (IUGR) rats. METHODS: IUGR was induced by maternal food restriction. The offspring (males and females) were assigned to: REF (non-IUGR, no mixture), IUGRc (IUGR, no mixture), or IUGRmx (IUGR, mixture). The mixture was given from day 7 to day 58, when tissues and plasma from half of the animals were collected for hormones, metabolites and microarray analysis. The rest received a high-fat diet (HFD) until day 100. Glucose tolerance was measured at 56 and 98 days, and body fat content at 21, 52 and 97 days. RESULTS: IUGRmx had the greatest growth during lactation, but from day 22 to day 54, both IUGR groups gained less body weight than the REF (P < 0.05). In the short-term (58 days), IUGRmx tended to be longer (P = 0.06) and had less body fat (P = 0.03) than IUGRc. These differences were not seen after HFD. Microarray analysis of hepatic mRNA expression at 58 and 100 days revealed a gender-dependent treatment effect, and expression of genes related to lipid metabolism was the most affected. Twelve of these genes were selected for studying differences in DNA methylation in the promoter region, for some, we observed age- and gender-related differences but none because of treatment. CONCLUSION: The nutritional intervention promoted catch-up growth and normalized excessive adiposity in IUGR animals at short-term. The benefits did not extend after a period of HFD. IUGR and early diet had gender-dependent effects on hepatic gene expression.

Antibiotic administration early in life impairs specific humoral responses to an oral antigen and increases intestinal mast cell numbers and mediator concentrations.

In this study, we assessed the effect of administering the antibiotic amoxicillin to rat pups on the immune response to orally fed ovalbumin (OVA). We first established that amoxicillin administration durably altered the gut microbiota of these animals. In parallel, we observed that the induction of the specific humoral response to ovalbumin was impaired when it occurred during antibiotic administration to the rat pups. We also examined the consequences of those observations on further allergic reactions. Amoxicillin administration had no significant impact on subsequent sensitization to OVA, as nonexacerbated systemic allergic responses were induced in antibiotic-treated animals. However, increased rat mast cell protease II levels and higher mast cell numbers were detected in their small intestines, independently of the antigen administration. Globally, our data suggest that antibiotic administration early in life negatively affects the specific immune response to a luminal antigen when it is first introduced during antibiotic administration. The increased mast cell numbers and mediator concentrations in the intestinal mucosae of the antibiotic-treated animals may testify to the early stages of an altered immune system homeostasis.

The digestion rate of protein is an independent regulating factor of postprandial protein retention.

To evaluate the importance of protein digestion rate on protein deposition, we characterized leucine kinetics after ingestion of "protein" meals of identical amino acid composition and nitrogen contents but of different digestion rates. Four groups of five or six young men received an L-[1-13C]leucine infusion and one of the following 30-g protein meals: a single meal of slowly digested casein (CAS), a single meal of free amino acid mimicking casein composition (AA), a single meal of rapidly digested whey proteins (WP), or repeated meals of whey proteins (RPT-WP) mimicking slow digestion rate. Comparisons were made between "fast" (AA, WP) and "slow" (CAS, RPT-WP) meals of identical amino acid composition (AA vs. CAS, and WP vs. RPT-WP). The fast meals induced a strong, rapid, and transient increase of aminoacidemia, leucine flux, and oxidation. After slow meals, these parameters increased moderately but durably. Postprandial leucine balance over 7 h was higher after the slow than after the fast meals (CAS: 38 +/- 13 vs. AA: -12 +/- 11, P < 0.01; RPT-WP: 87 +/- 25 vs. WP: 6 +/- 19 micromol/kg, P < 0.05). Protein digestion rate is an independent factor modulating postprandial protein deposition.

Neither glutamine nor arginine supplementation of diets increase glutamine body stores in healthy growing rats.

The aim of the work was to resolve whether glutamine and arginine supplemented diets affect plasma and tissue (muscle, liver and intestinal mucosa) glutamine concentrations, as well as glutaminase and glutamine synthetase specific activities. The trial was performed in growing rats fed 10% protein diets for 3 weeks. Protein sources were: whey proteins (W); whey proteins+free glutamine (WG); whey proteins+arginine (WA); and casein+wheat protein hydrolysate+acid whey (39:39:22), as source containing protein-bound glutamine (CGW). Rats fed the control diet (6.4% glutamine) (W) showed comparable glutamine body stores to those of rats fed the WG diet. In fact, glutamine sup- plementation down-regulated the hepatic glutamine synthetic capacity of growing rats (W/WG: 6.8+/-0.3 vs 6.0+/-0.2 nmol/min/mg protein). Arginine supplementation of the diet (up to 9% of the protein content) resulted in a decrease in plasma and tissue glutamine concentrations (W/WA: plasma, 1218+/-51 vs 1031+/-48 micromol/L; liver 7.5+/-0.4 vs 6.5+/-0.2 micromol/g; muscle: 5.7+/-0.2 vs 4.0+/-0.2 micromol/g). These data suggest that glutamine supplementation of the diet does not increase plasma and tissue glutamine concentrations in healthy growing rats, while the addition of arginine to the diet decreases glutamine body stores.