EP2701710A1

EP2701710A1 - Anti-inflammatory composition for the intestine including maltitol

Info

Publication number: EP2701710A1
Application number: EP12725070.2A
Authority: EP
Inventors: Laëtitia Guerin-Deremaux; Clémentine THABUIS; Daniel Wils
Original assignee: Roquette Freres SA
Current assignee: Roquette Freres SA
Priority date: 2011-04-28
Filing date: 2012-04-27
Publication date: 2014-03-05
Also published as: WO2012146881A1; FR2974512B1; FR2974512A1

Abstract

The present invention relates to a composition including at least maltitol for the treatment or prevention of intestinal inflammation, gastrointestinal infections, lesions, wounds or contusions of the tissue on at least one portion of the gastrointestinal tract of humans or animals.

Description

ANTI-INFLAMMATORY COMPOSITION OF INTESTINE

COMPRISING MALTITOL

The present invention relates to the use of maltitol in the treatment or prevention of inflammatory bowel disease.

The present invention also relates to a composition containing at least maltitol and at least one additional active agent for the treatment of Chronic Inflammatory Bowel Diseases, but also for persons suffering from irritable bowel syndrome, persons suffering from or abdominal pain whose etiology is often unknown; in the treatment of gastrointestinal cancers, infections ^¬ gastro intestinal lesions, wounds or bruises at least a portion of the gastrointestinal tract.

Chronic Inflammatory Bowel Diseases (or IBD) include two distinct conditions: ulcerative hemorrhagic rectocolitis (RCH) and Crohn's disease. These two diseases, both distinct and related, are characterized by more or less diffuse inflammatory lesions of the intestine, notably due to a state of hyperactivation of the immune system of the intestine whose origin is unknown.

The symptoms are mainly digestive, including diarrhea, abdominal pain, slimming, inflammation of the tissues.

The frequency of IBD has been increasing since the last few decades. This is partly explained by the technical progress made which makes it easier to diagnose diseases. It seems also clear that changing dietary habits is a factor in the evolution of these diseases, as are food allergies, obesity and other diseases of civilization.

Polyols are widely used in the replacement of sugar in confectionery because of their low calorie but especially acariogenic nature. More recently, the beneficial effect on the health of polyols has been widely recognized because of their hypoglycaemic and hypo-insulinemic character. Polyols therefore potentially have a beneficial effect in the context of cardiovascular diseases or diabetes, but also in the context of diseases related to obesity.

Their beneficial effect on health, however, has been studied very little outside that associated with oral health.

In this context, the Applicant has investigated the effect of polyols and more particularly maltitol in the health of the colon and more particularly an effect of polyols on inflammation of the colon.

The effect on the health of the colon of certain dietary fiber has been highlighted. In particular, fructo-oligosaccharides (FOS) or certain branched maltodextrins have shown an effect on inflammation of the colon. The effect of these polysaccharides would be through the induction of growth of lactobacilli, bacteroids and endogenous bifidobacteria of the gut in humans and animals.

Lactobacilli have the advantage of lowering the pH of the medium by producing lactic acid, which prevents the growth of pathogenic flora such as proteobacteria or enterobacteria, causative agents of pathologies such as Crohn's disease or certain ulcerative colitis.

Bifidobacteria and bacteroids are particularly described for their production of glucosidase-type enzymatic activities, which promote the release of flavonoids with antimutagenic and antioxidant effects.

The induction of intestinal flora can be demonstrated by the measurement of these glycolytic activities such as in particular alpha- and beta-glucosidases.

Inflammatory diseases and their respective treatment are the subject of active research. Experimental models for the induction of colitis have been developed, such as the induction of colitis by the administration of an allergen-containing solution (TriNitroBenzene Sulfonate or TNBS) in ethanol in rats or laboratory mice.

Ethanol allows the destruction of the barrier constituted by the intestinal mucosa and thus promotes the penetration of TNBS into the intestinal wall, and TNBS causes acute necrosis, often transmural, probably due to oxidative damage.

This model is considered for localized hypersensitivity studies of the colon, and is particularly appropriate in that the inflammations caused by this model are sensitive to drugs administered in the context of IBD.

Several anti-inflammatory bowel compositions have been proposed and tested using this animal model. The Applicant has demonstrated that maltitol has a curative and / or preventive effect on inflammation of the colon in animals and therefore, a priori, in humans.

The present invention thus relates to a composition comprising at least maltitol for use in treating or preventing at least one disorder selected from inflammation of the intestine, gastrointestinal infections, and lesions, wounds or bruises of at least a portion of the gastrointestinal tract in humans or animals.

Maltitol is only slightly digested and absorbed intestinal. Most of the maltitol ingested arrives as it is in the colon where it is fermented. The studies carried out by the Applicant have made it possible to demonstrate that the colonic fermentation of maltitol causes the modulation of certain parameters reflecting the overall state of health of the colon. The increase in colonic fermentations leads to an increase in the production of volatile fatty acids (VFA), thus increasing the rate of colonic bacteria and also the weight of the mucosa. It is indeed recognized in the scientific field that VGAs released in the colon have a beneficial effect on the intestinal mucosa (Salminen et al., 1998, Br J Nutr, Functionnal Food Science and Gastrointestinal Physiology and Function, Suzuki et al. 2008, Br J Nutr, Physiological concentrations of SCFA immediately suppressed colony epithelial permeability, Cherbut 2003, Proceedings of the Nutrition Society, Motor Effects of SCFA and Lactate in the GI tract).

Thus, without wishing to be bound by any theory, the association of different parameters modulated by the maltitol is probably the cause of the preventive and curative effect of maltitol on inflammation.

The Applicant has also highlighted the fact that maltitol promotes the development of bifidogenic bacteria to the detriment of unwanted bacteria. This has notably been revealed by the very significant increase in alpha- and beta-glucosidase and esterase activities.

The anti-inflammatory composition of the intestine according to the invention makes it possible to stimulate, by a factor of 1.1 to 10, preferably 1.2 to 6, even more preferably from 1.5 to 5.5, the enzymatic activities. alpha-glucosidase and / or fetal beta-glucosidase, as will be exemplified hereinafter.

This results in properties that are very beneficial for the health of the consumer.

On the other hand, the maltitol fermentation of the anti-inflammatory composition according to the invention by the microorganisms of the colon induces a lowering of the pH of the caecal, intestinal and faecal contents, which induces a balanced growth of said microorganisms.

The use of the anti-inflammatory composition according to the invention also makes it possible to increase the production of AGV in the colon and the coecum. These AGVs are especially chosen from the group consisting of acetic, butyric and propionic acid, preferably propionic and butyric acids. Typically, the anti-inflammatory composition according to the invention also makes it possible to increase the production of propionic acid by a factor of 1.5 to 3, preferably by a factor of 2 to 2.5. The protective effect of the colonic mucosa is demonstrated, particularly in animals, after administration of TNBS and results in remarkable results, as will be exemplified below.

Animals continue to eat normally, and are significantly protected against necrotizing inflammation induced by TNBS. It should also be noted that maltitol allows a maintenance of the caecal weight, an increase of the size of the colon and a decrease of the Wallace score after a TNBS treatment.

This effect significantly reflects the protective effect of said compositions against intestinal inflammation, making it possible to envisage the preparation of anti-inflammatory and / or analgesic compositions of the intestine improving the well-being of patients, both in humans. than animals.

The Applicant has also demonstrated that a daily amount of maltitol in the range 1.25 to 2.5 g / our / rat has a curative effect and / or preventive with respect to intestinal inflammation, gastrointestinal infections ^¬ intestinal lesions, lesions, wounds or bruises on at least part of the tissue of the gastrointestinal tract. Such a daily quantity corresponds in fact to a 5% and 10% dry mass intake (respectively 50g and 100g of maltitol / kg of food) in the diet of a rat or 5% (weight / volume) in the diet. drinking water from a rat.

Moreover, it has been demonstrated in humans that a daily dose of maltitol of less than 50 g / day does not induce undesirable symptoms (Koutsou GA et al., 1996, European Journal of Clinical Nutrition, 50: 17-21). According to an advantageous characteristic of the invention, the composition according to the invention is therefore provided, in the animal, at a rate of 0.5 to 10 g / day / animal, preferably 1 to 5 g / day / animal and, in 1 to 50 g / person, preferably 5 to 50 g / individual, more preferably 10 to 50 g / / individual.

According to an advantageous characteristic of the invention, the composition according to the invention also comprises at least one additional active agent, effective in the treatment or prevention of inflammation of the intestine and / or in the treatment or prevention of infections. ^¬ gastro intestinal lesions, sores or bruises of the gastrointestinal tract in humans and animals.

Typically, said additional active agent is chosen from suifasalazine, corticosteroids, atypical antidepressants, their derivatives and their mixtures.

According to another variant of the invention, the composition also comprises a prebiotic chosen from oligosaccharides, polysaccharides and mixtures thereof.

Typically, said prebiotic is selected from fructans, such as inulin and fructooligosaccharides (FOS); polydextrose; galacto-oligosaccharides (GOS); trans-galacto-oligosaccharides (TOS), xylo-oligosaccharides (XOS), branched maltodextrins, Acacia gum and mixtures thereof.

Preferably, the branched maltodextrins may be prepared according to the process described in patent EP 1 006 128. Advantageously, the composition according to the invention also comprises at least one other polyol chosen from lactitol, mannitol, sorbitol, xylitol, erythritol, arabitol and their mixtures.

According to one variant, the composition according to the invention also comprises a probiotic chosen from yeasts, preferably Saccharomyces cerevisiae, and bacteria, preferably chosen from Lactobacillus, Bifidobacterium, Escherichia coli, Bacillus and Enteroccocus.

According to an advantageous characteristic of the invention, the composition is in the form of sublingual, oral or rectal administration.

Preferably, the composition according to the invention is in the form of tablets, capsules, powders, granules, solutions or suspensions, emulsions or suppositories.

The invention also relates to the use of maltitol as a medicament.

The invention is also directed to a medicament comprising an effective dose of maltitol and a pharmacologically acceptable carrier for use in treating or preventing at least one disorder selected from inflammation of the intestine, gastrointestinal infections, and lesions and wounds. or bruising of at least a portion of the gastrointestinal tract in humans or animals.

For the purposes of the present invention, the term "effective dose" is understood to mean an amount of maltitol of 0.5 to 10 g / day / animal, preferably 1 to 5 g / day / animal and 1 to 50 g animal. / / individual, preferably 5 to 50 g / / individual, more preferably 10 to 50 g / / individual, in humans.

Advantageously, the invention also relates to a kit for the therapeutic or prophylactic treatment of the human or animal body comprising:

a) a first composition comprising maltitol, said composition being as described above, and

b) a second composition comprising an additional active agent effective in the treatment or prevention of inflammation of the intestine and / or in the treatment or prevention of gastrointestinal infections ^¬ intestinal lesions, wounds or bruises on the fabric at least a portion of the gastrointestinal tract in humans or animals.

The invention also provides a method of treatment and / or prevention of inflammation of the intestine and / or treating or preventing infections of the gastro intestinal ^¬, lesions, wounds or bruises on the fabric at least a portion ^¬ gastro intestinal tract in humans or animals, comprising a step of administering to a patient in need thereof a pharmaceutically effective dose of maltitol, the said maltitol is administered, alone or in mixture with at least one other additional active agent effective for the treatment or prevention of inflammation of the intestine and / or in the treatment or prevention of gastrointestinal infections ^¬ intestinal lesions, wounds or bruises on the fabric at least a portion of the tract gastrointestinal tract in humans or animals. Example 1

The metabolism of maltitol has been compared to that of glucose through a mid-term nutritional supplementation study. Maltitol was administered at a fixed dose of 10% by weight (dry / dry) in the food for 36 days (from day 1 to day 36) in the Sprague-Dawley rat. During this nutritional intervention, several physiological parameters were studied: blood, urine and feces were collected at the beginning and end of the intervention, analyzed and the results compared. At the end of the experiment, the animals were sacrificed and the cocees removed.

The purpose of dextrose control is to replace the 10% maltitol added to the standard diet with a 100% absorbed molecule in the small intestine.

Thus, a group of ten rats was subjected to an experimental diet where maltitol had been incorporated at a level of 10% by dry weight (100 g of maltitol / kg of food). Similarly, a second group of ten rats simultaneously received the same food where the 10% maltitol was replaced by 10% anhydrous dextrose. A third group (control group) consumed the rat maintenance staple for 36 days. At D0, the animals were randomized according to their weight and assigned to their respective groups. From Jl, the experimental diet started. The parameters studied during the study are as follows:

food consumption

- collection of faeces on D1 and D29 (determination of pH, dry matter and enzymatic activities) sample collection on day 36 (determination of pH, dry matter and dosage of volatile fatty acids or AGV). For the weight of the full and empty caecums and for the weight of the caecal content, the mean and the standard deviation were calculated. The batches were compared with each other by a variance analysis test (ANOVA).

For assay of AGV, assay of various biochemical parameters and assay of enzymatic activities, mean and standard deviation were calculated. The batches were compared with each other by an analysis of variance test.

For food and beverage consumption calculated and expressed per animal per day, mean and standard deviation were calculated.

The results show that the parameters measured at Jl do not make it possible to differentiate the different groups of rats.

After 6 weeks of maltitol supplementation, significant differences were observed for some parameters measured at D36.

The significant increase in the weight of the solid cecum (Table 1) shows that maltitol induces an increase in the cecal bacterial mass and that part of the maltitol administered is fermented in the colon and cecum.

This intestinal maltitol fermentation is also visible through the 88% increase in the level of propionic acid (Table 1). It is found that consumption of maltitol leads to an increase in total production of AGV in comparison with the control and dextrose groups, explaining the decrease in the pH of the observed Caecal content.

Table 1: Biochemical parameters measured in the caecum after supplementation with 10% maltitol in the food for 36 days.

n = number of animals per group; M = average; SD = standard deviation; Analysis of variance test: pl = control vs dextrose, p2 = control vs maltitol, p3 = dextrose vs maltitol; E = evolution of the group / value of the control group.

Fermentation of maltitol is not only observable in the cecum but also in the colon due to a decrease in the pH of faeces reflecting the colonic environment (Table 2). The increase of flora The beneficial effect of the colon is observable through a strong increase in the activity of alpha- and beta-glucosidases (respectively -gluc and β-gluc) and beta-galactosidase (β-gal) in the feces.

The activity of the enzymes (-gluc, β-gluc and β-gal) is evaluated according to the following test (this is also the case for Examples 2 and 3):

After thawing, the substrates are mixed and then put at 37 ° C in a thermostatically controlled water bath before use. The substrates are as follows: 5 mM nitrophenyl CC-D-glucopyranoside (Sigma); 5mM p-nitrophenyl β-D-glucopyranoside (Sigma); 5mM p-nitrophenyl β-D-glucuronide (Sigma) and 10mM p-nitrophenyl β-D-galactopyranoside (Sigma). They are prepared with phosphate buffer dihydrogenophosphate KH ₂ PO ₄ and frozen for a period of less than 2 months.

Samples are frozen after sampling. For the assay, they are thawed and then centrifuged at 14300 rpm for 3 minutes.

The assay is performed on a microplate.

Samples and controls are duplicated in the wells of the microplate. The controls are as follows: α-glucosidase (Maltase), activity: 5.8 U / mg (Fluka) at 0.40 g / l; β-glucosidase (cellobiase), activity: 66.6U / g (Fluka) at 7 g / l; β-galactosidase (lactase), activity: 11.8 U / mg at 0.50 g / l. Control solutions are prepared with osmosis water. The microplate is prepared as follows

1. Sample

Incubate at 37 ° C for 10 minutes in the plate reader. Then add:

SUBSTRATE 100 μΐ

2. Control

Incubate at 37 ° C for 10 minutes in the plate reader. Then add:

SUBSTRATE 100 μΐ

The microplate is read on the Spectra Max plus 384 spectrometer using SOFTMAX® software at a wavelength of 405 nm. The software is configured according to the following parameters:

Kinetic method

Time: 10 minutes 31 readings every 20 seconds

microplate agitated 5 seconds before the first reading, then shaken again for 3 seconds before each reading.

5 - Absorbance: 0 to 4 of D. O

The results are expressed in units of absorbance at 405 nm / minute / gram of faeces (wet or dry).

Table 2: Biochemical parameters measured in faeces after supplementation with 10% maltitol in the 29-day diet.

n = number of animals per group; M = average; SD = standard deviation; Variance analysis test: pl = control vs dextrose, p2 = control vs maltitol, p3 = dextrose vs maltitol; E = evolution of the group / value of the control group. After supplementation with maltitol at 10% in the food, the changes observed in the cecum and the level of the feces make it possible to conclude that the maltitol induces a fermentation at the level of the colon and the cecum. This fermentation causes growth of glycolytic bacteria in the colon and increased production of propionic acid. However, it is recognized in the scientific field that the volatile fatty acids released in the colon have a beneficial effect on the intestinal mucosa. This last point is observable through the increase in the weight of the empty cecum (Table 1).

Example 2

The previous study shows a beneficial effect of maltitol after a 10% supplementation in the food for 36 days. In this 2 ^nd example, a lower dose (5%) of maltitol and shorter administrations (17 and 28 days) were tested and compared to an equivalent maltodextrin supplementation (fully hydrolysed and digested in the small intestine as well as dextrose).

In addition, the effect of stopping the consumption of maltitol on the state of health of the colon and cecum was studied.

Administration of Administration of

Groups

D0 to D17 D17 to D28

Maintenance food + 5%

1

maltodextrin

2 maintenance food + 5% maltitol

Food Maintenance Food

3 of maintenance + 5% + 5% of

maltitol maltodextrin At OJ, the animals were randomized according to their weight and assigned to their respective groups. From Jl, the experimental diet started. The parameters studied during the study are as follows:

- food consumption

collection of faeces at OJ, J17, J19, J21 and J28 (determination of pH, dry matter and enzymatic activities)

sample collection on day 28 (determination of pH, dry matter and AGV determination).

For feed consumption, biochemical assays, pH measurement of dry matter and feces, an ANOVA was performed to highlight the statistically significant differences.

At OJ, the different study groups are similar for all parameters. Fecal samples throughout the supplementation allow longitudinal monitoring of certain fecal parameters.

After supplementation with 5% maltitol in the food for 17 or 28 days, the changes observed in the cecum (Table 3) and in the faeces (Table 4) confirm the results detailed in the example. 1, namely the beneficial effects of maltitol on the mucosa of the colon and cecum and this, from 5% in the food and from 17 days of supplementation. Table 3: Cecal Parameters at J28 Function

supplementation or not with 5% maltitol

n = number of animals per group; M = average; SD = standard deviation; Variance analysis test: p = group 2 or 3 vs group 1.

Table 4: Evolution of the enzymatic activity of the - glucosidase as a function of time and of the supplementation or not with 5% maltitol (Uabs / min / g of feces)

Consumption of maltitol for 17 days and then return to a diet supplemented with maltodextrin (fully digested in the small intestine) causes a return of different parameters to a basal level. Intestinal fermentation parameters return to baseline values between 2 and 4 days after stopping maltitol consumption.

The ^2nd example confirms that the maltitol consumption leads to improved health parameters the colon and cecum, and highlights the fact that this improvement is transient and does not disturb the balance of the ecosystem colic after cessation of consumption. The effects of maltitol are therefore reversible. Example 3

In this example, the effect of maltitol administered in the beverage at a dose of 5% for 24 days on bowel inflammation induced by intrarectal injection of TNBS (Trinitrobenzene Sulfonic Acid) was studied in rat Sprague. -Wawley. The administration of maltitol was performed via the drinking water to ensure the continuity of maltitol intake despite the injection of TNBS which was likely to degrade food intake. The dose of maltitol ingested by the animal remains the same as in Example 2, namely approximately 1.25 g / day / rat.

At J1, the animals were randomized according to their weight and assigned to their respective groups. From D0, the experimental diet started. The parameters studied during the study were the following: weight change

consumption of food and drink

collection of faeces at OJ, D21 and between D21 and D24 (determination of pH, dry matter and enzymatic activities)

colony collection at D24 (weight, height, Wallace score, myeloperoxidase assay)

sample collection at day 24 (determination of pH, dry matter)

For individual data (animal weighing, biochemical parameters), mean and standard deviation were calculated. The batches were compared with each other by a variance analysis test (ANOVA). For cage data (food and beverage consumption), mean and standard deviation were calculated. The Fisher and Student tests were done.

During the first 21 experimental days, the weight, food consumption and drinking parameters show no difference between the groups. Only a significant increase in the enzymatic activity 1'-glucosidase was demonstrated in the feces of the groups supplemented with maltitol (values expressed in absorbance units / minute / gram of dry faeces), in accordance with Examples 1 and 2 (Table 5). ). Table 5: enzymatic activity of 1 -glucosidase as a function of the supplementation or not with 5% of maltitol in the faeces collected on D21 (before the injection of TNBS)

n = number of animals per group; M = average; SD = standard deviation; Analysis of variance test: p (1/2) = group 1 vs group 2, p (1/3)

= group 1 vs group 3, p (3/4) = group 3 vs group 4, p (2/4) = group 2 vs group 4. During the first 21 days of intervention, the beneficial effect of maltitol on colonic and caecal mucosa was verified according to Examples 1 and 2. After these 21 days, the rats received intrarectal injections of TNBS (proinflammatory and necrotizing agent) or NaCl solution (control).

In both TNBS groups (Dextrose and Maltitol), the necrotic agent decreased feed consumption (between D21 and D24) compared with the saline injected groups (Table 6). Nevertheless, supplementation with maltitol allowed a smaller decrease in food intake after TNBS injection (Table 6). A protective effect of maltitol in the face of inflammation of the colon is thus demonstrated here.

Table 6: Cumulative food intake (g / day)

n = number of animals per group; M = average; SD = standard deviation; Analysis of variance test: p (1/2) = group 1 vs group 2, p (1/3) = group 1 vs group 3, p (3/4) = group 3 vs group 4, p (2 / 4) = group 2 vs group 4. Preventive maltitol supplementation maintained a high level of glucosidase activity (a and β) after TNBS injection (Table 7). Table 7: Enzymatic activities according to the supplementation or not with 5% maltitol in the faeces collected between D21 and D24 (after the injection of TNBS)

n = number of animals per group; M = average; SD = standard deviation; Analysis of variance test: p (1/2) = group 1 vs group 2, p (1/3) = group 1 vs group 3, p (3/4) = group 3 vs group 4, p (2 / 4) = group 2 vs group 4. Table 8: Evaluation of parameters related to the colon after the injection of TNBS or NaCl (size in cm, Wallace's score (SW) weight of the colon full or empty in g)

n = number of animals per group; M = average; SD = standard deviation; Analysis of variance test: p (1/2) = group 1 vs group 2, p (1/3) = group 1 vs group 3, p (3/4) = group 3 vs group 4, p (2 / 4) = group 2 vs group 4.

A protective effect of maltitol is visible through the tendency of Wallace scores to decrease between groups 2 and 4, as well as through the tendency of colon sizes to increase between group 4 and group 2. Intra-rectal injection of TNBS in rats causes very strong physiological disturbances. The results obtained on the coccal contents and the enzymatic activities of the faeces confirm the beneficial effects of maltitol fermentation observed in previous studies on healthy animals (examples 1 and 2).

The improvement of colic parameters by maltitol allows a better resistance to the onset of colic inflammation.

Claims

A composition comprising maltitol for use in treating or preventing at least one disorder selected from inflammation of the intestine, gastrointestinal infections, lesions, wounds or bruises of at least a portion of the gastrointestinal tract in the Man or the animal.

2. Composition according to claim 1, characterized in that it is administered, in the animal, at a rate of 0.5 to 10 g / day / animal, preferably 1 to 5 g / day / animal and, in the Male, at a rate of 1 to 50 g / / individual, preferably 5 to 50 g / / individual, more preferably 10 to 50 g / / individual.

3. Composition according to one of claims 1 or 2 characterized in that the composition also comprises at least one additional active agent.

4. Composition according to claim 3, characterized in that said additional active agent is selected from suifasalazine, corticosteroids, atypical antidepressants, their derivatives and mixtures thereof.

5. Composition according to any one of claims 1 to 4, characterized in that it also comprises a prebiotic selected from oligosaccharides, polysaccharides and mixtures thereof.

6. Composition according to claim 5, characterized in that said prebiotic is chosen from fructans, such as inulin and fructo-oligosaccharides (FOS), polydextrose, galacto-oligosaccharides (GOS), trans-galacto- oligosaccharides (TOS), xylo-oligosaccharides (XOS), branched maltodextrins, Acacia gum and mixtures thereof.

7. Composition according to any one of claims 1 to 6, characterized in that it also comprises at least one other polyol selected from lactitol, mannitol, sorbitol, xylitol, erythritol, arabitol and their mixtures.

8. Composition according to any one of claims 1 to 7, characterized in that it is in the form of sublingual administration, buccal or rectal.

9. Composition according to any one of claims 1 to 8, characterized in that it also comprises a probiotic selected from yeasts, preferably Saccharomyces cerevisiae, and bacteria, preferably selected from Lactobacillus,

Bifidobacterium, Escherichia coli, Bacillus and Enteroccocus.

10. Composition according to any one of claims 1 to 9, characterized in that it is in the form of tablets, capsules, powders, granules, oral solutions or suspensions, emulsions or suppositories.

11. A medicament comprising an effective dose of maltitol and a pharmacologically acceptable carrier for use in treating or preventing at least one disorder selected from gut inflammation, gastrointestinal infections, and wounds, wounds or bruises. at least a portion of the gastrointestinal tract in humans or animals.

12. Maltitol for use as a medicine.

13. Kit for therapeutic or prophylactic treatment of the human or animal body comprising:

a) a first composition comprising maltitol according to one of claims 1 to 10, and

b) a second composition comprising an additional active agent effective in the treatment or prevention of inflammation of the intestine, gastrointestinal infections ^¬ intestinal lesions, wounds or bruises on the fabric at least a portion of the gastro ^¬ intestinal tract in humans or animals.