The effects of a chronic load of nonabsorbable sugars on intracolonic bacterial metabolism of carbohydrates and on H2 breath excretion are disputed. However, most of the discussion relies on indirect evidence or on results of in vitro studies. Thus, we attempted to assess directly and in vivo the effects on intracolonic metabolism of lactulose of a chronic oral load of this nonabsorbable disaccharide. 20 g of lactulose was given orally twice daily during 8 d to eight normal volunteers. In all, breath H2 concentration was measured on days 1 and 8 after ingestion of the morning lactulose dose. In four subjects, stools were collected during 2 d at the beginning and at the end of the lactulose maintenance period to measure fecal pH and daily outputs of carbohydrates and P-galactosidase. The four other subjects were intubated on days 1 and 8 to measure the pH and the concentrations of carbohydrates, lactic acid, and volatile fatty acids (VFA) in the distal ileum and cecal contents.Moreover, '4C-lactulose was added to cold lactulose and "CO2 breath outputs determined. Pulmonary H2 excretion fell from day 1 to day 8 (P < 0.05), whereas '4CO2 excretion increased (P < 0.01). Fecal water pH, lactic acid, and VFA concentrations did not vary between the two stool collection periods. 24-h fecal weight, fecal water, and carbohydrate outputs showed a trend to decrease between days 1 and 2 and days 7-8, whereas jlgalactosidase activity rose markedly (P < 0.01). No significant variations were observed for all parameters measured in ileal fluid. In the cecum, areas under the concentration curves decreased from day 1 to day 8 for lactulose, galactose, and fructose (P < 0.01), while an increase was found for lactic acid (P < 0.001), acetic acid (P < 0.0001), and total VFA (P < 0.001). Cecal fluid pH dropped faster (P < 0.05) and to a lower level (P < 0.05) on day 8 than on day 1. These data clearly show that a chronic load of a nonabsorbable sugar induces changes in colonic bacterial metabolic pathways resulting in a better efficiency of the flora to digest the carbohydrate. Introduction Measurement of pulmonary hydrogen (H2) excretion is widely used to diagnose and quantify carbohydrate malabsorption (1-6). However the accuracy of the H2 breath test in the study of chronic carbohydrate malabsorption is debated (1). Perman et al. (7) showed that an 8-d oral administration of lactulose resulted in acidic stools and in a dramatic fall of H2 breath excretion after an oral load of this sugar or of lactose in lactase-deficient patients. From stool homogenate incubations with various sugars, these authors concluded that the fall of H2 production was due to an inhibition of bacterial carbohydrate metabolism by the low colonic pH (7). Unfortunately, they did not measure stool sugar outputs. If their statement was always true, lactose-H2 breath test could be erroneously normal in lactase-deficient patients ingesting every day large amounts of incompletely absorbed carbohydrates, including lactose itself. This is contradictory to the...

Lactoferrin (Lf) is a milk iron-binding glycoprotein that plays a role in iron transport and acts as both a bacteriostatic and a growth modulating agent. The aim of this study was to investigate the nature of immune responses induced by repeated oral administration of bovine milk Lf in mice. Groups of ten female BALB/c mice were fed daily for 4 weeks with two doses of protein antigen: a low (0·05 mg/g body weight per d) or high (1 mg/g body weight per d) dose of Lf, or water as a control. A fourth group was immunized intramuscularly with 0·01 mg Lf in complete Freund's adjuvant. Anti-Lf IgA and IgG were detected in the intestinal fluid and serum of mice given Lf. Total immunoglobulins were higher in the intestinal fluid in Lf groups than in the control group. No difference could be detected in the serum. IgA and IgG secretion was enhanced in Peyer's patches and spleen from Lf-fed mice, in comparison with controls. [3H] thymidine uptake into Peyer's patch and spleen cells from both control and Lf-fed mice was enhanced by 75 μg Lf/ml in vitro, but Lf groups had a greater proliferation rate than the control group. These findings suggested that Lf could act as an immunostimulating factor on the mucosal immune system and that activation of the mucosal immune system is dependent on the ability of Lf to bind to the intestinal mucosa.

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Food protein intake interacts with the immune system. In earlier nutritional and immunological studies, nutrients, particularly milk whey proteins, were generally administered in soluble form and by gavage. However, orogastric intubation does not represent a natural way of ingesting nutrients such as lactoferrin (Lf). We examined how different modes of oral administration of Lf could affect the regulatory effect of this molecule on intestinal and systemic immune responses. Groups of 10 female BALB/c mice were administered Lf daily for 6 wk. To address the influence of the oral modes of administration, mice were given Lf either in solution, by gastric intubation or in the drinking water, or as a powder, by buccal deposition or in the diet. Mucosal and systemic immune responses, including specific immunoglobulin (Ig) secretion, cell proliferation, and cytokine production, were analyzed and compared with those of naïve mice given water under the same conditions or positive control mice that were administered Lf by i.m. injection. The addition of Lf to the drinking water had no visible effect on the immune status. Gastric intubation, single buccal doses, and continuous doses of Lf in the diet stimulated transient systemic and intestinal antibody responses against Lf. All of these oral modes of Lf exposure biased mucosal and systemic T-cell responses toward Thelper (Th)2-types and elevated IgA production by mucosal cells. However, the less natural gastric intubation also promoted Th1-type responses as evidenced by serum IgG(2a) antibodies and the secretion of Th1 cytokine by mucosal and systemic T cells in vitro. Thus, one should carefully consider the oral mode of administration for understanding regulation of immune responses by food proteins such as Lf.