Patent Description:
An intense and prolonged sport activity is known to lead to an effort, which can even cause a more or less marked damage to the fibers of muscles subjected to said effort, depending on the intensity thereof. Furthermore, an intense and prolonged sport practice results in an overall inflammatory response by the immune system, which reacts to the muscle damages being caused. Under this circumstance, sport performances are reduced with an inevitable drop of efficiency.

A strenuous and infrequent exercise, especially with a marked eccentric component, can lead to exercise-induced muscle damage (EIMD). Research demonstrated that the eccentric exercise induces ElMD in that the muscle is subjected to excessive forced stretching and contraction, which exacerbate the mechanical overload, thereby causing a muscle injury as a microtrauma. ElMD symptoms comprise: delayed onset muscle soreness (DOMS), reduced resistance, swelling, increased concentrations of creatine kinase due to the cell membrane destruction, weakened vascular function, and reduced glucose supply. These symptoms occur at any moment from <NUM> hours up to <NUM> days after exercise and are related to an increase of both inflammation and circulating leukocytes. The injured muscle attracts leukocytes in the area, and neutrophils and macrophages thus release ROS and pro-inflammatory cytokines in order to repair the damaged area. TNF-α is responsible for muscle proteolysis, and is upregulated by IL-<NUM>. Other cytokines such as NF-κβ are also stimulated by ROS. The damaged tissue is thus repaired and adapted, becoming more resistant to subsequent eccentric loads being applied.

By "muscle damage" is thus meant the loss of functionality of one or more muscles, which can be temporary, i.e. destined to be completely recovered within a more or less long period of time via the normal physiological processes for repairing muscle tissues, or it may have permanent effects of reduced, even partial, functionality.

By "exercise" is meant a sport, recreational, playing, working, locomotor or different activity, which comprises muscular movements and is, at least potentially, able to provoke a muscle injury, as defined above, in subjects performing it, in particular, but not limited to subjects with no specific training for such muscular movements.

<CIT> discloses a probiotic composition, used to treat e.g. muscle degeneration, muscle aches, fatigue and muscle pain, and to promote synthesis of ATP, comprising two or more bacterial strains selected from Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus bulgaricus, Lactobacillus gasseri, Lactobacillus reuteri, Lactobacillus paracasei, Lactobacillus casei, Lactobacillus acidophilus, Lactobacillusfermentum, Lactobacillus salvarius, Lactococcus lactis Streptococcus thermophilus, Bifidobacterium breve, Bifidobacterium bifidum, Bifidobacterium animalis subsp. lactis), Bifidobacterium animalis subsp. animalis (B. animalis), Bifidobacterium infantis, Bifidobacterium longum and Bifidobacteriumpseudocatenulatum.

Therefore, it would be very useful to have a natural, effective, easy-to-take remedy devoid of side effects for health, intended for all the subjects performing a strenuous and infrequent sport or exercise.

The Applicant, following to an intense and prolonged research and development activity, suitably met the above-cited needs.

The invention is defined by the appended claims <NUM>-<NUM>.

Within the context of the present invention by the composition(s) of the present invention is meant to encompass pharmaceutical compositions, compositions for medical devices, compositions for supplement products as well as food, nutraceutical and functional compositions.

The Applicant developed a composition comprising a mixture which comprises or, alternatively, consists of at least a strain of bacteria belonging to the species Bifidobacterium breve and at least a strain of bacteria belonging to the species Streptococcus thermophilus, said composition being for use in attenuating or reducing or eliminating the decline in sport performance after exercise, which can lead to a muscle damage.

The strains of bacteria belonging to the species Bifidobacterium breve, being object of the present invention, are selected due to their capability to inducing the synthesis of Interleukin <NUM> (IL-<NUM>), which exerts an anti-inflammatory effect pro-Th2, in order to act and re-establish a proper Th1/Th2 ratio (balance).

The strains of bacteria belonging to the species Streptococcus thermophilus, being object of the present invention, are selected due to their capability, along with the strains of bacteria belonging to the species Bifidobacterium breve, to inducing the reduction/decrease of Interleukin <NUM> (IL-<NUM>), which exerts a pro-inflammatory effect pro-Th1, in order to act and re-establish a proper Th1/Th2 ratio (balance).

The Applicant carried out an accurate selection of some species of bacteria belonging to the genus Lactobacilli and Bifidobacteria and, after several attempts, succeeded to detect the species Bifidobacterium breve and the species Streptococcus thermophilus.

Among the many strains of bacteria belonging to the species Bifidobacterium breve, the strain of bacteria Bifidobacterium breve BR03 (DSM <NUM>) deposited on <NUM>/<NUM>/<NUM> by Anidral Srl (presently Probiotical SpA) showed to be very interesting in inducing the increase of IL-<NUM>, an anti-inflammatory cytokine. The selected strain of bacteria B. breve, being object of the present invention, which is the strain of bacteria Bifidobacterium breve BR03, induces a marked increase of T helper lymphocytes and the secretion of Th2 cytokines (IL-<NUM> and IL-<NUM>) and also has a remarkable anti-inflammatory property due to the shift of the Th1/Th2 balance towards a Th2 response.

Among the many strains of bacteria belonging to the species Streptococcus thermophilus, the strain of bacteria Streptococcus thermophilus FP4 (DSM <NUM>) deposited on <NUM>/<NUM>/<NUM> by Mofin Srl showed to be very interesting in inducing the reduction of IL-<NUM>, a pro-inflammatory cytokine. The selected strain of bacteria S. thermophilus, being object of the present invention, which is the strain of bacteria Streptococcus thermophilus FP4 (DSM <NUM>), induces a marked reduction of cytokines Th1 (IL-<NUM>) secretion, which shifts the Th1/Th2 balance towards a Th1 response.

The supplementation with a composition of the present invention which comprises a mixture comprising or, alternatively, consisting of a strain of bacteria Bifidobacterium breve BR03 (DSM <NUM>) and a strain of bacteria Streptococcus thermophilus FP4 (DSM <NUM>) is capable of reducing inflammation, by lowering the inflammatory response and attenuating the decline in performance after exercise. The two strains of bacteria are present in the mixture in a weight ratio of <NUM>:<NUM>.

The composition of the present invention can further comprise additives, flavors, pH stabilizers and excipients or ingredients of pharmaceutical or food grade.

The strains of bacteria can be coated, encapsulated, or filmed, with a lipid layer, for example a plant lipid layer, in order to favoring both the intake and the absorption, for example at intestinal level. The strains of bacteria belonging to the species Bifidobacterium breve and the species Streptococcus thermophilus are present in a concentration of <NUM>×<NUM><NUM> CFU/g, based on the total weight of the composition according to the present invention.

It is an object of the present invention a composition comprising a mixture, which comprises or, alternatively, consists of the strains of bacteria Bifidobacterium breve BR03 (DSM <NUM>) and Streptococcus thermophilus FP4 (DSM <NUM>) in a weight ratio of <NUM>:<NUM>, in an amount of <NUM>×<NUM><NUM> CFU/g, each strain.

The composition of the present invention is effectively used in the event of prolonged exercise, which damages the muscle fibers.

Said composition is for therapeutic use, namely in subjects which experienced a muscle injury or are at risk thereof or, alternatively, for non-therapeutic use, i.e. for subjects who do not suffer from a specific pathological condition and are not at specific risk to contracting it.

It is an object of the present invention the non-therapeutic use of a composition comprising a mixture which comprises or, alternatively, consists of at least a strain of bacteria belonging to the species Bifidobacterium breve and at least a strain of bacteria belonging to the species Streptococcus thermophilus for attenuating or reducing or eliminating the decline in performance after exercise, wherein said use comprises the oral administration of said composition to a subject who performed said exercise, wherein said strain of bacteria belonging to the species Bifidobacterium breve is the strain of bacteria Bifidobacterium breve BR03 deposited at the DSMZ Institute with the No. DSM <NUM>, wherein said strain of bacteria belonging to the species Streptococcus thermophilus is the strain of bacteria Streptococcus thermophilus FP4 deposited at the DSMZ Institute with the No. DSM <NUM>, wherein the strains of bacteria Bifidobacterium breve BR03 (DSM <NUM>) and Streptococcus thermophilus FP4 (DSM <NUM>) are present in a weight ratio of <NUM> : <NUM> and in an amount of <NUM> × <NUM><NUM> CFU/g, each strain.

Advantageously, said use is for non-therapeutic purposes, i.e. is not related to the therapeutic or preventive treatment of diseases or disorders, in particular involving the musculature, in subjects suffering from such diseases or disorders and/or at risk to contracting them.

In a preferred embodiment, said strains of bacteria are in encapsulated form, i.e. coated with at least a lipid layer. As a non-limiting example, said lipid layer can be of plant origin and/or having a melting point comprised from <NUM> to <NUM>.

In a preferred embodiment, in the use according to the present invention, the composition comprises the strains of bacteria Bifidobacterium breve BR03 (DSM <NUM>) and Streptococcus thermophilus FP4 (DSM coated with a lipid layer as described above.

In a preferred embodiment, in the use according to the present invention, the composition advantageously enhances exercise during training and sport practice.

In a preferred embodiment, in the use according to the present invention, the exercise is an intense and prolonged sport activity, which results in an effort damaging the muscle fibers and/or musculature in general.

Alternatively, the composition can be for therapeutic use, namely for alleviating or preventing muscle damages in subjects who performed efforts, which can potentially damage the muscle tissues.

It is an object of the present invention a composition comprising a mixture which comprises or, alternatively, consists of at least a strain of bacteria belonging to the species Bifidobacterium breve and at least a strain of bacteria belonging to the species Streptococcus thermophilus, for use in reducing the overall inflammatory response by the immune system after muscle- damaging exercise, wherein said strain of bacteria belonging to the species Bifidobacterium breve is the strain of bacteria Bifidobacterium breve BR03 deposited at the DSMZ Institute with the No. DSM <NUM>, wherein said strain of bacteria belonging to the species Streptococcus thermophilus is the strain of bacteria Streptococcus thermophilus FP4 deposited at the DSMZ Institute with the No. DSM <NUM>, wherein the strains of bacteria Bifidobacterium breve BR03 (DSM <NUM>) and Streptococcus thermophilus FP4 (DSM <NUM>) are present in a weight ratio of <NUM> : <NUM> and in an amount of <NUM> × <NUM><NUM> CFU/g, each strain.

In a preferred embodiment, said strains of bacteria are in encapsulated form, namely coated with at least a lipid layer. As a non-limiting example, said lipid layer can be of plant origin and/or having a melting point comprised from <NUM> to <NUM>.

In a preferred embodiment, in the composition for use according to the present invention, said strains of bacteria Bifidobacterium breve BR03 (DSM <NUM>) and Streptococcus thermophilus FP4 (DSM <NUM>) are coated with a lipid layer as described above.

Said composition for use according to the present invention reduces the overall inflammatory response by the immune system.

In a preferred embodiment, said composition for use according to the present invention is able to shift the Th1/Th2 balance towards a Th2 response.

In order to determine the effect of a composition of the present invention comprising a mixture based on a strain of bacteria Bifidobacterium breve BR03 (DSM <NUM>) and a strain of bacteria Streptococcus thermophilus FP4 (DSM <NUM>) on the inflammatory response and the subsequent performance following to an intense period of muscle-damaging exercise, repeated, randomized, double-blind, placebo-controlled two-way measurements were used. The composition according to the invention reduces the inflammation and allows a greater adaptation to the training and subsequent increases in sport performances. The effect of the intake of said composition on inflammation and muscle performance following to an intense period of muscle-damaging exercise was studied.

The randomized, double-blind, placebo-controlled crossover method was applied to sixteen healthy resistance-trained men (<NUM> ± <NUM> years; <NUM> ± <NUM>; <NUM> ± <NUM>) which daily took the composition with the strains of bacteria in encapsulated form, said composition containing <NUM>×<NUM><NUM> CFU/g of B. breve BR03 (DSMZ <NUM>) and <NUM>×<NUM><NUM> CFU/g of S. thermophilus FP4 (DSMZ <NUM>) (PRO) or placebo (PLA) before performing (<NUM> days) an exercise, which damages the elbow flexors.

The performance of elbow flexors and an inflammatory marker (interleukin-<NUM>) were measured before and after the muscle-damaging exercise. A <NUM>-day wash-out period separated the conditions. A standardized magnitude-based inference to define outcomes was used.

The effects of both the treatment and time on the dependent variables of interest by a mixed model ANOVA using SPSS V. <NUM> (IBM Corporation; Armonk, NY) were assessed. The approach to the magnitude-based inference was used. This approach allows to solving problems concerning the estimates of the extent of the effect of a large sample with reference to precision (width of the confidence interval) relative to the minimal significant change for the considered outcome.

Results advantageously show that the intake of the composition, being object of the present invention, with the strains of bacteria in encapsulated form (strains coated with a single lipid coating of plant origin having a melting point comprised from <NUM> to <NUM>) containing <NUM>×<NUM><NUM> CFU/g of B. breve BR03 (DSMZ <NUM>) and <NUM>×<NUM><NUM> CFU/g of S. thermophilus FP4 (DSMZ <NUM>) attenuated the decline in performance at <NUM> (effect size [ES] = <NUM>), <NUM> (ES = <NUM>) and <NUM> hours (ES = <NUM>) post-exercise, measured by the average peak torque. Said composition exhibited an overall anti-inflammatory effect (ES = <NUM>).

Advantageously, the supplementation with said tested composition attenuates the decline in performance and subsequent inflammation following to an intense period of muscle-damaging exercise. The composition of the present invention is capable of attenuating or reducing or eliminating the decline in performance after exercise, typically observed after an intense period of muscle-damaging exercise and decreasing the related inflammatory response, measured by interleukin-<NUM> (IL-<NUM>).

The inclusion criteria in the study comprised: (<NUM>) attending to structured resistance training for <NUM> year before the test; (<NUM>) abstaining from nutritional supplement products or ergogenic aids during the <NUM> weeks before the test; and (<NUM>) abstaining from anti-inflammatory drugs during the previous month.

The study was carried out according to the guidelines of the Helsinki Declaration and registered at ClinicalTrials. gov: NCT02520583).

All the procedures involving human subjects were approved by the Institutional Review Board at Texas Christian University for the use of human subjects in research (protocol No. <NUM>-<NUM>-<NUM>). All the subjects provided a written consent.

A randomized, double-blind, placebo-controlled crossover research design for determining the effect of a first administration of probiotic strains B. breve BR03 and S. thermophilus FP4 on the subsequent performance and the acute inflammatory response following to a training session with muscle damage was used. Prior to the experimental test, a basal blood sample was taken from fasting subjects, before to be randomly assigned to orally intake for <NUM> days, as a supplement product, either a probiotic composition containing a mixture of <NUM> billions of live cells (AFU) of S. thermophilus FP4 (DSMZ <NUM>) and <NUM> billions of live cells (AFU) of B. breve BR03 (DSMZ <NUM>) (Probiotical S. , Novara, Italy; Probiotic), based on a previous dose regimen study, or a placebo.

Materials of the study were analyzed by Biolab Research S. , Novara, Italy, through flow cytometry (Biolab research method <NUM>-<NUM>, standardized by ISO <NUM>: <NUM> IDF <NUM>: <NUM> and accredited by Accredia, Roma, Italy, > <NUM> billions of live cells), and the plate count method (Biolab Research method <NUM>-<NUM>, > <NUM> billions CFU), confirming the count of the target cells.

At least <NUM> hours before the experimental test, subjects were familiarized with the procedure of experimental assessment (isometric strength).

The first experimental test started at least <NUM> days after the beginning of the probiotic or placebo administration. Subjects were instructed to abstain from any non-daily living activity during the <NUM> before the test.

Furthermore, subjects were instructed to abstain from any food, which could interfere with the study procedures. The day of the experimental test, the subjects, fasting from at least <NUM>, were placed in a supine position for inserting the catheter in order to allowing multiple blood withdrawals. After taking a basal blood sample, the upper arm circumference, range of motion and pain of the subjects were assessed prior to a warm-up, followed by the determination of the isometric strength.

Then the subjects performed a session of eccentric exercises of the elbow flexors, which are known to cause muscle damages. The initial limb was randomly selected. Immediately after the eccentric exercise, a second blood sample was taken, and the isometric strength was determined again. Subjects were thus placed in a supine position for <NUM>. Blood samples were obtained <NUM> and <NUM> after the session of eccentric exercise. One hour post-exercise, the upper arm circumference, range of motion, and pain were assessed again.

Subjects were re-examined at <NUM>, <NUM>, and <NUM> hours following to the session of eccentric exercise for a blood withdrawal, and the assessment of the upper arm circumference, range of motion, and pain, followed by the determination of the isometric strength. After a <NUM>-day wash-out, subjects repeated the experimental protocol with administration of the supplement product alternative to that previously taken.

(namely, who previously received the placebo, took the probiotic in the second session, and vice versa) and using the contralateral limb.

The maximal voluntary isometric peak torque of the elbow flexors was measured at a joint angle of <NUM>° on an isokinetic dynamometer (Biodex System <NUM>, Shirley, NY, USA). Prior to determining the maximal isometric torque, subjects performed a warm-up of <NUM> sets of <NUM> repetitions, from <NUM>° to <NUM>° at two different speeds (<NUM>° s-<NUM> and <NUM>° s-<NUM>, respectively) resting for <NUM> between sets. Then, subjects performed two tests of maximal isometric torque of elbow flexors, each of <NUM> separated by <NUM> of rest between tests. Verbal encouragement as well as a real-time display of power were provided throughout the exercise for encouraging the achievement of the maximum efforts.

Following to a warm-up and the determination of the isometric strength, subjects performed <NUM> sets of <NUM> maximal eccentric contractions (forced stretching) at a speed of <NUM>°x s-<NUM>. After every forced eccentric contraction, from <NUM>° to <NUM>°, the research staff brought the arm back to the starting position at a speed of <NUM>° s-<NUM> (<NUM>), so that no concentric contraction was performed by the subject. Sets were one minute-separated, and subjects were encouraged throughout the exercise. The same research technician was assigned for all the studies involving the same subject.

At the day of the eccentric exercise session, subjects were placed in a supine position for inserting the catheter. The area was sterilized according to standard withdrawal procedures and a catheter (BD Biosciences, San Jose, CA, USA) was inserted in an antecubital vein and capped for multiple blood withdrawals. The catheter was kept patent by fluxing <NUM>-<NUM> of <NUM>% sodium chloride (G-Biosciences, St. Louis, MO, USA) injected in the withdrawal site.

Prior to each blood withdrawal from the catheter, a <NUM> Vacutainer (BD Biosciences, San Jose, CA, USA) was used for taking a sample to be discarded. A blood sample is obtained before starting the administration of the test composition and <NUM> days later, prior to the performance of the eccentric exercise session. Since then, blood was immediately taken post-exercise and <NUM> and <NUM> later. Blood samples were also withdrawn at <NUM>, <NUM> and <NUM> post-exercise. Blood samples were collected in <NUM> EDTA tubes (BD Biosciences, San Jose, CA, USA).

Blood samples were centrifuged by <NUM> from collection for <NUM> at 2000x g in a refrigerated centrifuge (<NUM>). Plasma aliquots were then immediately transferred and frozen at -<NUM> until further analyses. The plasma samples were analyzed for IL-<NUM> concentrations by using a human IL-<NUM> high sensitivity ELISA Kit (R & D Systems, Minneapolis, MN, USA). The detection range for this test was from <NUM> pg. mL<NUM> to <NUM> pg. The inter- and intra-assay coefficients of variation for each test were of less than <NUM>%.

Raw data are presented as mean and standard deviation. All the data, except for visual analog scale data, were log-transformed before analysis for managing a non-uniformity of error. The treatment effects and the treatment x time on outcomes were assessed by a mixed-model analysis of variance (Proc Mixed, SAS <NUM>, Cary, NC, USA), with the subject term as the random effect. Estimates of log-transformed analysis were presented as back log-transformed least-squares means or adjusted geometric means with uncertainty (<NUM>% confidence interval, CI).

As regards inference, a magnitude-based approach was used. A numerical translation of performances in the experimental model to the actual power of performance is unknown, with the isometric torque as the research design for investigating the proof of principle. Therefore, the smallest standardized difference was considered the smallest main change for the primary and related mechanistic results. In the present case, the magnitude threshold for the smallest change was the Glass' d standardized difference (<NUM> x the baseline SD for the control condition).

The likelihood that a contrast was at least greater than the relative thresholds was of <NUM>% -<NUM>% for low likelihood, <NUM>%-<NUM>% likely, <NUM>%-<NUM>% very likely, > <NUM>% almost certain. If most (> <NUM>%) of the confidence interval (IC) occurred between thresholds for a positive and negative substantiality, the effect was scored as trivial (negligible). The terms beneficial, trivial, and harm relate to the most likely directional result, relative to the minimal effect threshold. The term unclear relates to outcomes wherein the likelihood is greater than <NUM>% for both benefits and damages.

After the <NUM>-day supplementation, the average peak torque was significantly lower (<NUM>%; <NUM>% Cl <NUM>, <NUM>%) following to probiotics relative to placebo (<FIG>). Decline in performance was observed after exercise under both the conditions, proving the efficacy of the damage-inducing protocol.

The administration of the composition according to the invention significantly enhanced the production of maximal mean isometric torque at <NUM> and <NUM> hours after the harmful physical activity, as compared to pre-exercise (<FIG>. probiotic-placebo effect and <NUM>% Cl, likelihood % benefit/ trivial/ harms:.

<FIG> shows the effect of a <NUM>-day administration of probiotics and placebo on the mean isometric peak torque before and during <NUM> hours following to the eccentric load of the exercise. <FIG> shows the probiotic-placebo difference with an adjusted score for the basal value (pre-eccentric exercise). Data in <FIG> are the raw means and SD. Data in <FIG> are the probiotic-placebo effect as placebo percentage and <NUM>% confidence intervals derived from the mixed-model analysis of variance.

Horizontal dotted lines are the smallest thresholds of standardized difference (+ <NUM>%), whereas the likelihood of substantial change is included above the contrast represented by ** = likely; *** = very likely; outcomes with no stars are inconclusive or unclear.

The main finding of the present study was that the <NUM>-day administration of probiotics according to the invention attenuated the decline in performance following to an exercise session which causes, or can cause, muscle damaging.

The administration of probiotics according to the present invention leads to a greater resting arm angle relative to placebo. It was proved that the administration of prebiotics according to the invention actually increases the resting arm angle as compared to placebo at <NUM> and <NUM> hours.

IL-<NUM> concentration decreases following to the <NUM>-day administration of probiotics according to the invention, while no increase with placebo was observed.

Data of the present study show that the prebiotic administration, without a concurrent administration of proteins, attenuates the decline in muscle performance, since a greater isometric peak torque was observed relative to placebo during the several recovery days after eccentric contractions of stretching. It follows that with the composition according to the invention the administration of prebiotics alone was shown for the first time to attenuate the decline in muscle performance.

Specific reference to <FIG>, <FIG> is made.

The percentage change in peak torque (<FIG>), average peak torque (<FIG>), and average peak torque relative to the body weight (<FIG>) during the isometric flexion of the elbow are shown below. The threshold for the minimal substantial change was calculated as <NUM> times the baseline SDbetween. Likelihood is shown as an increased occurrence of symbols (+) relative to placebo (PLA): + possible, ++ likely, +++ very likely, ++++ highest likelihood. All the data are an average.

The reduction of about <NUM>% in the ability of power generation underlines the efficacy of the muscle-damaging protocol in stimulating the required response. The supplementation with the tested composition (p=<NUM>) attenuated the decline in performance observed after a muscle-damaging exercise, <NUM> hours after an intense exercise period (<FIG>). With the average peak torque, a benefit at <NUM> hours (p=<NUM>), <NUM> hours (p=<NUM>), and <NUM> hours (p=<NUM>) was observed. Similarly, the average peak torque relative to the body weight showed a benefit from the supplementation of the tested composition at <NUM> hours (p=<NUM>), <NUM> hours (p=<NUM>), and <NUM> hours (p=<NUM>).

Inflammation was assessed by changes in IL-<NUM> following to an intense period of muscle-damaging exercise. However, since the effect of the tested composition in decreasing the overall inflammatory response, IL-<NUM> was evaluated at the baseline before the supplementation period. Indeed, supplementation with the strains of bacteria B. breve BR03 (DSMZ <NUM>) and S. thermophilus FP4 (DSMZ <NUM>) provided a reduction effect on IL-<NUM>, as shown by a decrease in the percentage change from the baseline in subjects supplemented with said strains of probiotic bacteria (-<NUM>%) as compared to an increase after placebo (<NUM>%). Furthermore, the difference (contrast) between the percentage change in IL-<NUM> between placebo and probiotic was likely at <NUM> minutes (p = <NUM>), <NUM> minutes (p = <NUM>), and <NUM> hours (p = <NUM>) after muscle-damaging exercise, whereas it was probably lower (p = <NUM>) <NUM> hours later.

The <NUM>-day administration of probiotics according to the invention, in healthy and resistance-trained subjects attenuates the decline in performance and range of motion following to a muscle-damaging exercise session. These data suggest that the oral administration of probiotics according to the invention can help in recovering the performances after an intense physical effort, even in untrained or poorly trained subjects.

From the above, it results that the composition of the present invention comprising a mixture which comprises or, alternatively, consists of at least a strain of bacteria belonging to the species Bifidobacterium breve and at least a strain of bacteria belonging to the species Streptococcus thermophilus, attenuates the decline in performance observed after a muscle-damaging exercise. This effect is due to a reduction of the overall inflammation, as confirmed by a decreased IL-<NUM> after supplementation.

Claim 1:
A non-therapeutic use of a composition which comprises or, alternatively, consists of at least a strain of bacteria belonging to the species Bifidobacterium breve and at least a strain of bacteria belonging to the species Streptococcus thermophilus in attenuating or reducing or eliminating the decline in performance after exercise, wherein said use comprises the oral administration of said composition to a subject who performed said exercise, wherein said strain of bacteria belonging to the species Bifidobacterium breve is the strain of bacteria Bifidobacterium breve BR03 deposited at the DSMZ Institute with the No. DSM <NUM> wherein said strain of bacteria belonging to the species Streptococcus thermophilus is the strain of bacteria Streptococcus thermophilus FP4 deposited at the DSMZ Institute with the No. DSM <NUM>, wherein the strains of bacteria Bifidobacterium breve BR03 (DSM <NUM>) and Streptococcus thermophilus FP4 (DSM <NUM>) are present in a weight ratio of <NUM> : <NUM> and in an amount of <NUM> × <NUM><NUM> CFU/g, each strain.