Composition for reducing intestinal gas production

Abstract

The present invention relates to a composition comprising Bifidobacterium bacteria for use for reducing intestinal gas production in an individual.

Claims

1. A method for reducing intestinal gas production in an individual comprising administering a composition comprising Bifidobacterium animalis bacteria to the individual, wherein the individual's exhaled breath comprises at least 10 ppm H.sub.2 under fasting conditions.

2. The method of claim 1, further comprising administering the Bifidobacterium animalis bacteria prior to, with, or subsequent to consumption of a flatulogenic food by the individual.

3. The method according to claim 1, wherein the Bifidobacterium animalis bacteria belong to the Bifidobacterium animalis subspecies lactis.

4. The method according to claim 1, wherein the Bifidobacterium animalis bacteria belong to the strain deposited under reference number CNCM I-2494.

5. The method according to claim 1, wherein the composition is a dairy composition.

6. The method according to claim 5, wherein the dairy composition is a fermented dairy composition.

7. The method according to according to claim 1, wherein the composition further comprises at least one flatulogenic food.

8. The method according to claim 7, wherein the flatulogenic food comprises at least one ingredient of lactulose, lactose, fructose, xylose, arabinose, fructans, stachyose, raffinose, melibiose, manninotriose, inuline, starch, sorbitol, mannitol, or xylitol.

9. The method according to claim 1, further comprising administering the Bifidobacterium animalis bacteria prior to consumption of a flatulogenic food by the individual.

10. The method according to claim 1, further comprising administering the Bifidobacterium animalis bacteria subsequent to consumption of a flatulogenic food by the individual.

11. The method according to claim 2, wherein the flatulogenic food comprises at least one ingredient of lactulose, lactose, fructose, xylose, arabinose, fructans, stachyose, raffinose, melibiose, manninotriose, inuline, starch, sorbitol, mannitol, or xylitol.

12. The method according to claim 1, further comprising treating at least one digestive symptom of the individual associated with intestinal gas production.

13. The method according to claim 1, wherein the intestinal gas is post-prandial or digestive intestinal gas.

14. The method according to claim 1, wherein the composition comprises from 10.sup.8 and to 10.sup.11 colony forming unit (CFU) of the Bifidobacterium animalis bacteria.

15. The method according to claim 14, further comprising administering the composition at least once daily for at least 1, 2, 3, or 4 weeks.

16. The method of claim 1, wherein the composition is a fermented dairy composition and comprises from 10.sup.8 and to 10.sup.11 CFU of the Bifidobacterium animalis, and further comprising administering the composition at least once daily.

17. The method of claim 16, wherein the composition further comprises Lactobacillus bulgaricus and Streptococcus thermophilus.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 represents the mean change in hydrogen (H.sub.2) breath levels (vertical axis, in ppm) elicited by consumption of lactulose in subjects which have a basal H.sub.2 breath level of at least 10 ppm (right panel), and in subjects which have a basal breath level of less than 10 ppm (left panel). The change is the difference between H.sub.2 breath levels after and before consumption of a control composition (control; left bar of each panel; black) or the test composition (Fermented Milk Product with Probiotic (FMPP); right bar of each panel; grey).

(2) FIG. 2 represents the mean change in the composite score of eight (8) gastro-intestinal (GI) symptom levels (vertical axis, numerical score) elicited by consumption of lactulose in subjects which have a basal H.sub.2 breath level of at least 10 ppm (right panel). The change is the difference between the composite score of 8 GI symptoms after and before consumption of a control composition (control; left bar; black) or the test composition (FMPP; right bar; grey).

EXAMPLE

(3) Material and Methods

(4) Subjects and Study Design

(5) IBS patients or subgroups of IBS patients are generally considered an appropriate study group to substantiate claims on gastro-intestinal discomfort intended for the general population by the European Food Safety Authority (EFSA Journal 2011; 9(4):1984). All participants were subjected to a combined nutrient and lactulose challenge test for the assessment of gastrointestinal symptoms and the amount of exhaled H2 as objective marker of intestinal gas production. Adult subjects fulfilling Rome III criteria for irritable bowel syndrome (IBS) were prospectively included at a tertiary care outpatient clinic. The diagnosis was based on a typical clinical presentation and additional investigations if considered necessary. Classification into IBS subtypes according to Rome III criteria was done based on Bristol Stool Form scale characteristics: IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), mixed IBS (IBS-M) or unsubtyped IBS (IBS-U) (Table 1). All participants, aged between 18 and 65 years at inclusion visit, gave their written informed consent and were allowed to withdraw from the study at any time. Exclusion criteria included the use of probiotics or antibiotics during the study or within one month before the inclusion, severe psychiatric disease and history of drug or alcohol abuse.

(6) The study was a single centre, randomized, double-blind and controlled parallel-group design in which 100 subjects consumed (125g/serving) twice a day either the test composition or a control composition for 14 days. The test composition was a fermented milk, containing Bifidobacterium animalis deposited at the Collection Nationale de Culture de Microorganismes (CNCM, Paris, France) under the Budapest Treaty under reference CNCM I-2494 (1.25?10.sup.10 colony forming unit (cfu) per serving) together with the two classical yoghurt starters, S. thermophilus and L. bulgaricus (1.2?10.sup.9 cfu/serving). The test composition was unflavoured. The control composition was a milk-based non-fermented dairy product without probiotics and with low content of lactose<4 g/pot (as in the test composition). Each serving of either test or control composition contained 125 g.

(7) A lactulose challenge test (see below) was performed in all subjects prior to and following the intervention period of 14 days.

(8) TABLE-US-00001 TABLE 1 Clinical characteristics at baseline for study subjects. Mean (95% Cl) IBS (n = 100) Age (range) 34.4 (32.1-36.7) Gender (F/M) 61/28 BMI 23.0 (22.4-23.7) IBS-C (n) 19 IBS-D (n) 32 IBS-M (n) 35 IBS-U (n) 14 PI-IBS (n) 17 BMI: body mass index; IBS-C: irritable bowel syndrome with constipation; IBS-D: irritable bowel syndrome with diarrhea; IBS-M: irritable bowel syndrome with mixed pattern; IBS-U: irritable bowel syndrome unsubtyped; PI-IBS: post-infectious IBS.
Lactulose Challenge Test

(9) All participants arrived to the laboratory in the morning (7:30-8:00 a.m.) after an overnight fast. They had been instructed to avoid consumption of food containing dietary fibers the day before the test. The lactulose challenge test meal (400 ml Nutridrink?, 1.5 kcal/ml, 16% proteins, 49% carbohydrates, 35% fat, gluten free, lactose<0.025 g/100 ml, combined with 25 g of lactulose) was served at 8:00 a.m. The 25 g lactulose dose was chosen according to the outcome of our previous pilot study (Le Nev? et al. (2013) Am J Gastroenterol. 108(5):786-95). The severity of eight GI symptoms, the overall digestive comfort and the amount of exhaled H.sub.2 as objective marker of intestinal gas production were assessed every 15 min starting 30 min before the test meal and during 4 h following meal intake. The amount of exhaled H.sub.2 was measured in parts per million (ppm). All breath samples were end-expiratory, collected in a system used for the sampling and storing of alveolar air (GaSampler system, QuinTron Instrument Company, Milwaukee, Wis., USA) and analyzed immediately using a gas chromatograph (QuinTron Breath Tracker, QuinTron Instrument Company, Milwaukee, Wis., USA).

(10) Questionnaires

(11) The severity of eight GI symptoms (flatulence, bloating, abdominal discomfort, abdominal distension, nausea, stomach rumbling, abdominal pain and urgency to have a bowel movement) and the level of digestive comfort were assessed at baseline (T0) and every 15 min during the lactulose challenge test using 20-point numerical rating scales, with 0 corresponding to no sensation and 20 corresponding to the most intense sensation imaginable for the symptoms, and with 0 corresponding to extremely uncomfortable, 10 corresponding to neutral and 20 corresponding to extremely comfortable for digestive comfort.

(12) Statistical Analysis

(13) A classification of the study subjects was made before the ingestion of the test meal containing lactulose during the first lactulose challenge test. The classification of subjects was made considering a cut-off at 10 ppm for basal H.sub.2 breath levels. Subjects with a basal production of H.sub.2 lower than 10 ppm were considered normal H.sub.2 producers whereas subjects with a basal production of H.sub.2 equal to or higher than 10 ppm were considered high H.sub.2 producers. Table 2 represents the repartition of study subjects during the intervention between groups according to this basal H.sub.2 breath level classification.

(14) TABLE-US-00002 TABLE 2 Contingency table between basal H.sub.2 breath level classification of subjects and intervention groups Test Control composition composition basal H.sub.2 breath level <10 ppm 29 38 basal H.sub.2 breath level ?10 ppm 21 12

(15) The change of each parameter: severity of 8 individual GI symptoms, composite score of 8 GI symptoms, level of digestive comfort, exhaled H.sub.2, was evaluated by an Analysis Of Variance (ANOVA) model taking into account three factors: Intervention group: test composition or control composition Basal H.sub.2 breath level: <10 ppm H.sub.2 or ?10 ppm H.sub.2 Interaction between intervention group and basal H.sub.2 breath level

(16) The significance of the main effects intervention group and basal H.sub.2 breath level were evaluated at a 0.05 significance level. The interactions between intervention group and basal H.sub.2 breath level were evaluated at a 0.10 significance level. Least squares means comparison was done on the interaction between intervention group and basal H.sub.2 breath level only if this interaction was significant at the defined threshold. For parameters where the interaction was statistically significant, least squares means comparison was also done on intervention group even if this main effect was not statistically significant to evaluate the magnitude of the effects in each basal H.sub.2 breath level compared to the global population. The equality of variance in each group was assessed by the test of Bartlett. The normality of the residuals was assessed by kurtosis and skewness values. The kurtosis and skewness values had to be in the range of [?2, 2]. The main parameter considered was the equality of variance in each group. In case the equality of variance was verified but not the normality of residuals, a non-parametric Kruskall Wallis test was performed to confirm the results, but the ANOVA model results were kept if both outcomes had the same significativity.

(17) Results

(18) The inventors classified the study subjects in two groups (see statistical section above): A basal high H.sub.2 producer group (n=33, n.sub.test=21, n.sub.control=12), with at least 10 ppm breath H.sub.2 before ingestion of the test meal comprising lactulose; A basal low H.sub.2 producer group (n=67, n.sub.test=29, n.sub.control=38), with less than 10 ppm breath H.sub.2 before ingestion of the test meal comprising lactulose.

(19) Changes in breath H.sub.2 and in gastro-intestinal (GI) symptoms elicited by a lactulose challenge test before and after intervention (i.e. consumption of the test composition or the control composition) are shown in FIGS. 1-2.

(20) Briefly, in basal high H.sub.2 producers, intestinal gas production following a lactulose challenge test was significantly reduced by the consumption of the test composition as compared to the control composition. This is evidenced by a reduction in mean breath H.sub.2 of 15.6%. In contrast, no such reduction of intestinal gas production could be evidenced in subjects with basal low H.sub.2 production (FIG. 1).

(21) This effect on intestinal gas production was paralleled by a decrease in the severity of the eight gastro-intestinal (GI) symptoms for subjects with basal high H.sub.2 production. This is evidenced by a reduction in the mean composite score for the eight GI symptoms of 17.4% in basal high H.sub.2 producers consuming the test composition as compared to the control composition (see FIG. 2).