Limosilactobacillus mucosae and disorders requiring a glp-1 increase

Abstract

The present invention relates to a bacterial strain of the species Limosilactobacillus mucosae , or a lysate or culture supernatant thereof, for use in the prevention and / or treatment of disorders requiring an increase in GLP-1 production in a subject in need of GLP-1, the disorders being selected from (i) a disorder related to dysregulation of insulin sensitivity and / or blood glucose concentration and (ii) loss of muscle mass and / or muscle function.

Description

[0001] Description

[0002] Title: Limosilactobacillus mucosae and disorders requiring increased GLP-1 levels

[0003] Technical field

[0004] The present invention relates to novel probiotic and prebiotic agents for stimulating the synthesis of GLP-1 by intestinal cells.

[0005] In particular, the invention relates to a bacterial strain of the species Limosilactobacillus mucosae, or a lysate or a culture supernatant thereof for use in the prevention and / or treatment of disorders requiring an increase in the level of GLP-1 in a subject in need thereof, said disorders being chosen from (i) a disorder linked to a deregulation of insulin sensitivity and / or blood sugar and / or (ii) loss of muscle mass and / or muscle function. It also relates to the non-therapeutic use of a bacterial strain of the species Limosilactobacillus mucosae, for maintaining or increasing muscle mass and / or function in a subject in need thereof, in particular in a subject selected from a malnourished subject, an elderly subject, in particular a malnourished elderly subject, and a subject practicing intense physical exercise.Finally, the invention relates to the bacterial strain Limosilactobacillus mucosae deposited with the CNCM under accession number CNCM 1-5661.

[0006] Prior art

[0007] The proportion of elderly people (65 years and over) is expected to represent a third of the French population by 2050. This population is very heterogeneous and is characterized, at the extremes, by healthy, active individuals in good nutritional status, with little sarcopenia (age-related loss of muscle mass and function) and generally living at home. Conversely, there is (at the same age) an elderly population that is malnourished and highly sarcopenic, generally dependent and living in institutions and in a state of chronic undernutrition (Buckinx et al., Burden of frailty in the elderly population: perspectives for a public health challenge. Archives of public health = Archives beiges de santé publique. 2015;73(1): 19). At the same time, in some Western countries, overweight or obese individuals represent more than half of the population.A portion of this population, in addition to an increased susceptibility to developing diabetes or cardiovascular pathologies, may also present increased muscle wasting which can reduce the autonomy of these people and especially limit the room for maneuver during obesity treatments through the use of low-calorie diets (Barazzoni et al., Sarcopenic Obesity: Time to Meet the Challenge. Obesity facts. 2018; 11(4):294-305). In addition, the loss of muscle mass and function can also affect individuals at times during their lives, depending on their background and experiences. This is particularly the case for "major burn" patients, those immobilized, cancer patients, or those who have undergone intestinal resection or who have intestinal malabsorption.

[0008] Recent data suggest a causal link between the activity of the gut microbiota and various pathologies related to deregulation of nutrient metabolism and insulin resistance (Marchesi et al. The gut microbiota and host health: a new clinical frontier [Review], Gut. 2016 Feb;65(2):330-9). These data thus suggest the interest of developing probiotic strategies. In addition, comparative physiology studies focus on pathophysiological situations where individuals presented metabolic adaptations favorable to the preservation of insulin sensitivity, muscle mass and / or to a better efficiency of metabolic utilization of nutrients.

[0009] It has been observed that certain lactobacilli are over-represented in individuals who have undergone intestinal resection (Mayeur et al. Extensive Intestinal Resection Triggers Behavioral Adaptation, Intestinal Remodeling and Microbiota Transition in Short Bowel Syndrome [Review], Microorganisms. 2016 Mar 8;4(1)). The digestive tract and microbiota of these patients have the particularity of having adapted metabolically to maintain their energy-nitrogen anabolism despite reduced intestinal absorption capacities of food (Gillard et al. Enhanced Ghrelin Levels and Hypothalamic Orexigenic AgRP and NPY Neuropeptide Expression in Models of Jejuno-Colonic Short Bowel Syndrome. Scientific reports. 2016 Jun 21;6:28345).

[0010] A study of the transfer of these bacteria to axenic rats showed an increase in the concentrations of plasma peptides such as leptin, ghrelin and GLP-1, suggesting an increase in insulin sensitivity and an increase in the efficiency of energy recovery in these animals (Gillard L, Mayeur C, Robert V, et al. Microbiota Is Involved in Post-resection Adaptation in Humans with Short Bowel Syndrome. Frontiers in physiology. 2017;8:224). Indeed, GLP-1, a digestive peptide produced by enteroendocrine cells of the distal ileum and colon following meal ingestion, has numerous metabolic effects including the regulation of insulin secretion by the pancreas (but also of food intake and transit) (Laurindo et al. GLP-1a: Going beyond Traditional Use. Int J Mol Sci. 2022 Jan 10;23(2)).GLP-1 analogues are currently being used to improve glucose tolerance in patients, and a role for GLP-1 in Parkinson's disease and the regulation of mood disorders has even been suggested. GLP-1 receptor agonists are frequently used to treat type 2 diabetes and obesity (Laurindo et al. GLP-1a: Going beyond Traditional Use. Int J Mol Sci. 2022 Jan 10;23(2). Their use has also been suggested in many other disorders such as appetite regulation (Aldawsari et al., “The Efficacy of GLP-1 Analogues on Appetite Parameters, Gastric Emptying, Food Preference and Taste Among Adults with Obesity: Systematic Review of Randomized Controlled Trials.” Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 16 (2023): 575-95), liver disease (Newsome et al., “A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis.”New England Journal of Medicine 384, no 12 (25 mars 2021): 1113 24), ou les maladies dégénératives tel qu’ Alzheimer (Femminella et al., « Evaluating the Effects of the Novel GLP-1 Analogue Liraglutide in Alzheimer’s Disease: Study Protocol for a Randomised Controlled Trial (ELAD Study) ». Trials 20, no 1 (3 avril 2019): 191) ou la maladie de Parkinson (Athauda et al., « Exenatide Once Weekly versus Placebo in Parkinson’s Disease: A Randomised, Double-Blind, Placebo-Controlled Trial ». Lancet (London, England) 390, no 10103 (7 octobre 2017): 1664 75).

[0011] In particular, some GLP-1 agonists have been shown to have a beneficial impact on body composition, including the preservation of muscle mass, including, but not limited to, obese or diabetic individuals (Osaka et al., “Favorable Appendicular Skeletal Muscle Mass Changes in Older Patients With Type 2 Diabetes Receiving GLP-1 Receptor Agonist and Basal Insulin Co-Therapy.” Clinical Medicine Insights: Endocrinology and Diabetes 16 (January 1, 2023): 11795514231161884 or Hong et al., “Amelioration of Muscle Wasting by Glucagon-like Peptide-1 Receptor Agonist in Muscle Atrophy.” J Cachexia Sarcopenia Muscle 10, no. 4 (August 2019): 903 18) or elderly individuals (Abdulla et al., “Glucagon-like Peptide 1 Infusions Overcome Anabolic Resistance to Feeding in Older Human Muscle”. Aging Cell 19, no 9 (2020): e!3202).If bacteria resident in the distal part of the intestine (colon, distal ileum) are able to stimulate endogenous GLP-1 synthesis, all the metabolic effects associated with GLP-1 and described above can be expected.

[0012] The beneficial effects of certain bacteria of the genus Lactobacillus on humans are known in the art. For example, it is known that L. reuteri, through different mechanisms and metabolites, is capable of controlling body weight and obesity, or of improving insulin sensitivity and glucose homeostasis (Abuqwider et al. Limosilactobacillus reuteri in Health and Disease. Microorganisms 2022, 10, 522). In addition, it has been shown, for example, that the bacterial strain L. fermentum MG4295 can improve hyperglycemia in mice fed a high-fat diet and that this bacterial strain has properties favorable for its use as a probiotic (Kim et al., Limosilactobacillus fermentum MG4295 Improves Hyperglycemia in High-Fat Diet-Induced Mice. Foods 2022, 11, 231).

[0013] Furthermore, it is known in the art that certain strains of the species L. mucosae could present probiotic potentials, for example on lipid metabolism and in particular on the control of hyperlipemia (CN111979145 A1), but also in the treatment of memory disorders, learning disorders, mental disorders and inflammatory diseases (EP 3 715 449 A2) or even in protection against certain cardiovascular diseases (Ryan et al., BMC Microbiology (2019) 19:33).

[0014] However, to the inventors' knowledge, it has never been suggested in the past that a bacterial strain of the species L. mucosae could exhibit probiotic properties allowing the prevention and / or treatment of disorders requiring an increase in the production of GLP-1 in a subject in need thereof.

[0015] Thus, there remains a need to propose new probiotic compositions capable of stimulating the production of GLP-1, for the purposes of, depending on the subjects concerned, (i) preventing or treating a disorder linked to a deregulation of insulin sensitivity and / or glycemia or (ii) preventing or treating a loss of muscle mass and / or a loss of muscle function.

[0016] Disclosure of the invention Surprisingly, it is shown in the examples that a bacterial strain of the species Limosilactobacillus mucosae, or a lysate or culture supernatant thereof, induces, or increases, the production of the GLP-1 protein, in particular by the intestinal cells of a human subject.

[0017] According to a first subject, the invention relates to a bacterial strain of the species Limosilactobacillus mucosae, or a lysate or a culture supernatant thereof, for its use in the prevention and / or treatment of disorders requiring an increase in the production of GLP-1 in a subject in need thereof, said disorders being chosen from (i) a disorder linked to a deregulation of insulin sensitivity and / or glycemia and (ii) the loss of muscle mass and / or muscle function.

[0018] According to a particular embodiment, the subject in need thereof is a subject having an indication for an administration based on GLP-1 receptor agonists. In particular, a subject having an indication for an administration based on GLP-1 receptor agonists is chosen from the list consisting of insulin-resistant subjects such as diabetic subjects, overweight subjects, in particular obese subjects, subjects having undergone metabolic surgery, subjects seeking to regulate their appetite, subjects suffering from liver diseases, subjects suffering from cardiovascular pathologies, in particular suffering from cardiovascular pathologies linked to diabetes, subjects suffering from inflammation, in particular inflammation linked to diabetes and / or to a metabolic syndrome, subjects affected by sarcopenia, subjects affected by cachexia; and subjects suffering from neurodegenerative diseases.

[0019] According to one embodiment, the disorder is a disorder linked to a deregulation of insulin sensitivity and / or blood sugar selected from prediabetes, type 1 diabetes and type 2 diabetes.

[0020] According to one embodiment, the disorder is a loss of muscle mass and / or function and in that the subject in need thereof is chosen from elderly subjects affected by sarcopenia, overweight subjects and obese subjects affected by sarcopenic obesity and subjected to a diet, diabetic or prediabetic subjects, and / or subjects affected by cachexia, in particular linked to cancer, inflammatory bowel disease or chronic obstructive pulmonary disease, immobilization, a situation of "major burns", septic or having suffered a viral infection, convalescence and / or immobilization, and / or intestinal resection or intestinal malabsorption.

[0021] In particular, the bacterial strain is selected from the strain of the species L. mucosae deposited with the CNCM under accession number CNCM 1-5661, the strain of the species L. mucosae deposited with the DSM under accession number DSM 13345, the strain of the species L. mucosae deposited with the DSM under accession number DSM 13346, the strain of the species L. mucosae deposited with the DSM under accession number DSM 102820, or a mixture thereof, and in particular is the strain of the species Z. mucosae deposited with the CNCM under accession number CNCM 1-5661.

[0022] According to one embodiment, the bacteria of the species L. mucosae are in a living or dead form, preferably in a living form.

[0023] In particular, the bacterial strain may be included in a composition comprising a physiologically acceptable medium, in particular in an oral composition, and more particularly in an oral composition chosen from the group consisting of a food product, a beverage, a pharmaceutical product, a nutraceutical, a food additive, a food supplement, a dairy product and a living biotherapy product (LBPs).

[0024] Particulièrement, la composition comprend en outre une ou plusieurs autres souches bacteriennes probiotics, en particulier choisies parmi les species Bifidobacterium longum, Bifidobacterium lactis, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium adolescentis, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus salivarius, Lactobacillus johnsonii, Lactobacillus salivarius, Lactococcus lactis, Enterococcus faecium, Enterococcus faecalis, Saccharomyces cerevisiae, Saccharomyces boulardii, Faecalibacterium prausnitzii, Akkermansia muciniphila, Blautia faecis, Faecalibacteium prausnitzii, Streptococcus Thermophilus ou leurs mélanges, de préférence choisis dans le groupe constitue par Bifidobacterium longum NCC3001 (ATCC BAA-999), Bifidobacterium longum NCC2705 (CNCM 1-2618), Bifidobacterium longum NCC490 (CNCM 1-2170), Bifidobacterium lactis NCC2818 (CNCM 1-3446), Bifidobacterium breve souche A, Lactobacillus johnsonii NCC533 (CNCM 1-1225),Enterococcus faecium SF 68 (NCC2768; NCIMB10415), Lactobacillus casei (CNCM 1-5662 and CNCM 1-5663), Streptococcus thermophilus (CNCM I-5334) and combinations thereof. According to a particular embodiment, the composition is free of any other bacteria of the Lactobacillus species.,

[0025] In particular, the composition further comprises one or more prebiotics.

[0026] According to a second subject, the invention relates to the non-therapeutic use of a bacterial strain of the species Limosilactobacillus mucosae, or a lysate or a culture supernatant thereof, in particular as defined according to the invention, for maintaining or increasing muscle mass and / or function in a subject in need thereof, in particular in a subject selected from a malnourished subject, an elderly subject, in particular a malnourished elderly subject, and a subject practicing intense physical exercise.

[0027] Finally, the invention relates to the bacterial strain Limosilactobacillus mucosae deposited with the CNCM under accession number CNCM 1-5661.

[0028] Brief description of the drawings

[0029] [Fig 1] represents the concentration of GLP-1 in the supernatant of neuroendocrine intestinal cells of SCT-1 mice after 4h of incubation in the presence of the different bacteria and conditions tested. The x-axis represents the different conditions tested, namely, from left to right: strain 1 (L. casei 7), strain 2 (L. casei 2), strain 3 (L. camelliae), strain 4 (L. salivarius), strain 5 (L. rhamnosus), strain 6 (L. reuleri), strain CNCM 1-5661 (L. mucosae) and the control (negative - in sterile cell medium). The y-axis provides the GLP-1 concentration in pg / mL.

[0030] [Fig 2] represents the concentration of GLP-1 in the supernatant of neuroendocrine intestinal cells of SCT-1 mice as a function of incubation time in the presence of strain CNCM 1-5661 (L. mucosae). The x-axis represents the incubation time, namely, from left to right: 3h incubation, 4h incubation and 5h. The y-axis provides the GLP-1 concentration in pg / mL.

[0031] [Fig 3] represents the concentration of GLP-1 in the supernatant of neuroendocrine intestinal cells of SCT-1 mice after 3 hours of incubation in the presence of different bacteria of the species L. mucosae at different bacterial concentrations. The x-axis represents the different conditions tested, namely, from left to right: the control (negative control, sterile cell medium), the strain Lacticaseibacillus casei (strain A - negative control, ~5.10 9 CFU / mL), strain CNCM 1-5661 (strain B - positive control, -5.10 9CFU / mL), the CNCM 1-5661 strain diluted to 1 / 10 ème (diluted strain B - -5.10 8 CFU / mL), strain DSM 13345 (strain C - -2.10 9 CFU / mL), strain DSM 13345 diluted 1 / 10 ème (diluted C strain - -2.10 8 CFU / mL), strain DSM 13346 (strain D — 4.10 9 CFU / mL), the DSM 13346 strain diluted to 1 / 10 ème (diluted strain D — 4.10 8 CFU / mL), strain DSM 102820 (strain E - -5.10 9 CFU / mL), and strain DSM 102820 diluted to 1 / 10 ème (diluted E strain — 5.10 8CFU / mL). The y-axis provides the GLP-1 concentration in pg / mL. Significant difference (P<0.05). Same comment as before, there is a clear difference between the total absence of detected secretion (for the negative control conditions) and the detectable secretion of GLP-1 in the conditions with Z. mucosae bacteria, all strains combined, but no statistics were calculated (not enough data) and did not seem necessary to us in view of the results.

[0032] [Fig 4] represents the weight of the hind leg muscles of rats (in mg / g of rat) for different groups of aged rats (20 months) after one month of study. The groups of rats studied are, from left to right, on the x-axis: rats fed ad libitum (AL), rats restricted to 75-80% of ad libitum (R), rats restricted and supplemented with Z. mucosae of the CNCM-I5661 strain (R+L mucosae 15561), rats restricted and supplemented with Z. casei (R+L casei).

[0033] Detailed description

[0034] The inventors have conducted extensive work to identify the ability of a species of bacteria, the species Limosilactobacillus mucosae, to treat and / or prevent disorders requiring an increase in the production of GLP-1 in a subject in need thereof.

[0035] Indeed, the inventors unexpectedly showed that strains of Limosilactobacillus mucosae were able to stimulate GLP-1 synthesis by intestinal cells in vitro while other strains of distinct lactobacillus species are not able to induce this GLP-1 synthesis by intestinal cells. Furthermore, Limosilactobacillus mucosae showed a good capacity for resistance to environmental conditions encountered in the intestine (acidic stomach pH and bile salts) as well as a good capacity for adhesion to intestinal cells. Limosilactobacillus mucosae is abundant in patients with short bowel syndrome (Joly et al, biochemistry 2010; PMID: 20172013) and is able to colonize a virgin digestive tract (axenic animal) after fecal transfer (Gillard et al; Front Physiol. 2017); This indicates that this species is a commensal of the digestive tract.This ability of Limosilactobacillus mucosae to increase the synthesis of the intestinal peptide GLP-1 and to be present in the digestive tract is important because this peptide has many metabolic pleiotropic effects in the host, in particular, it improves insulin secretion by the pancreas, promotes glucose tolerance and therefore optimizes / improves the energy and nitrogen metabolisms of the host. Finally, the inventors have shown that the administration of a strain of Limosilactobacillus mucosae made it possible to increase muscle mass in a sarcopenic rodent model.

[0036] Limosilactobacillus mucosae

[0037] The present invention relates to the use of a bacterial strain of the species Limosilactobacillus mucosae, or a lysate or culture supernatant thereof.

[0038] For the purposes of the present invention, the term “lysate” is used indifferently to designate the entire lysate obtained by lysis of the microorganism concerned or only a fraction of it.

[0039] Obtaining dead bacterial cells can be carried out by any method known to those skilled in the art.

[0040] Bacterial cell lysate is formed in whole or in part from intracellular biological constituents and constituents of cell walls and membranes. It contains in particular the cellular cytoplasmic fraction containing enzymes such as lactic acid dehydrogenase, phosphatases, phosphoketolases and transaldolases. For example, the constituents of cell walls are in particular peptidoglycan, murein or mucopeptide and teichoic acid and the constituents of cell membranes are composed of glycerophospholipids.

[0041] A bacterial cell lysate can be obtained by various technologies, such as, for example, by exposing the bacterial cells to osmotic shock, thermal shock, or ultrasound. More particularly, this lysate can be obtained according to the technology described in US patent 4,464,362.

[0042] For the purposes of the present invention, the term "culture supernatant" refers to the culture medium in which the bacterial strains have remained during their culture, which may also be referred to as "extracellular medium" in the present description. In particular, the culture supernatant may comprise the metabolites produced and secreted by the bacterium, also called extracellular metabolites. Examples of metabolites are, for example, peptides, glycopeptides or lipopeptides produced by the bacterium. The culture supernatant may be crude or may have undergone one or more steps to filter it, concentrate it, freeze-dry it, heat it, etc. These techniques for transforming the culture supernatant of a bacterium are known to those skilled in the art.

[0043] The composition of the culture supernatant varies depending on the bacterial strain's cell culture conditions and processes. It mainly includes extracellular metabolites when the biomass is growing or only active. But also potentially intracellular metabolites for cultures at the end of the stationary phase and when microbial lysis is significantly higher. Some of the cells are dead and some have lost their membrane integrity by lysis, as a result of which the supernatant will include cell walls from the dead cells but also intracellular metabolites.

[0044] Furthermore, the culture supernatant may further comprise bacterial cells of the species Limosilactobacillus mucosae, in live or dead form.

[0045] Limosilactobacillus mucosae is a rod-shaped bacterial species of lactic acid bacteria first isolated from pig intestines. It exhibits mucus-adhesive activity.

[0046] Limosilactobacillus mucosae is a strict anaerobic Gram-positive bacterium, which can, however, multiply to a reduced extent in the presence of oxygen. This bacterial species is described in particular by Roos et al. (2000, International Journal of Systematic and Evolutionary Microbiology, Vol. 50 (1): 251-258). This bacterial species is described in the human microbiota of patients with short bowel syndrome (Drastic changes in fecal and mucosa-associated microbiota in adult patients with short bowel syndrome. Joly F, Mayeur C, Bruneau A, Noordine ML, Meylheuc T, Langella P, Messing B, Duée PH, Cherbuy C, Thomas M. Biochimie. 2010 Jul;92(7):753-61)

[0047] Regarding the designation of some probiotics, and in particular bacteria of the genus Lactobacillus, it is important to note the recent changes in their taxonomic classification, as reported in the article by Zheng et al. (2020, Int. J Syst Evol Microbiol, Vol. 70: 2782-2858). Thus, some probiotics of the genus Lactobacillus documented in the literature published prior to these taxonomic changes are now designated according to the new nomenclature in force.

[0048] Thus, the bacterial species known today as Limosilactobacillus mucosae can also be defined in the literature as Lactobacillus mucosae.

[0049] A bacterial strain of L. mucosae suitable according to the invention may be derived from feces of subjects suffering from short bowel syndrome.

[0050] According to a particular embodiment, a bacterial strain according to the invention is chosen from the strain of the species L. mucosae deposited with the CNCM under accession number CNCM 1-5661, the strain of the species Z. mucosae deposited with the DSM under accession number DSM 13345, the strain of the species L. mucosae deposited with the DSM under accession number DSM 13346, the strain of the species Z. mucosae deposited with the DSM under accession number DSM 102820, or a mixture thereof, and in particular is the strain of the species L. mucosae deposited with the CNCM under accession number CNCM 1-5661.

[0051] According to a particular embodiment, the bacterial strains of the species L. mucosae are in a living or dead form, preferably in a living form.

[0052] For the purposes of the invention, the term "dead bacterial strain" means a bacterial cell that is definitively no longer capable of multiplying and consequently of forming a colony in culture. Unlike a lysate, a dead bacterial strain can retain all of its membrane integrity.

[0053] A dead bacterial strain can be obtained by any known cell death method. According to a particular embodiment of the invention, the dead bacterial cells according to the invention can in particular be obtained by exposure to high heat (for example by exposure to a UHT protocol).

[0054] Thus, for the purposes of the present invention, and in particular in the examples of the present text, the term "living", unless otherwise indicated, designates living bacterial cells, including stabilized bacterial cells, that is to say viable and revivable bacterial cells (by all known stabilization methods, for example by freezing, freeze-drying or spray drying).

[0055] Compositions The present description also relates to a composition comprising a bacterial strain of the species Limosilactobacillus mucosae, or a lysate or a culture supernatant thereof.

[0056] Thus, according to a particular embodiment, a bacterial strain according to the invention is included in a composition comprising a physiologically acceptable medium.

[0057] The term "physiologically acceptable medium" is intended to designate a medium that is compatible with the organism of the individual to whom said composition is to be administered. It may be, for example, a non-toxic solvent such as water. The medium may also be a food, in particular when the bacterial strain according to the invention is included in a nutritional composition, as defined below. The medium may also be a mucus, such as snail mucus. A mucus suitable as a medium according to the present invention may in particular be obtained as described in Gillard et al. (Enhanced Ghrelin Levels and Hypothalamic Orexigenic AgRP and NPY Neuropeptide Expression in Models of Jejuno-Colonic Short Bowel Syndrome, Sci Rep. 2016 Jun 21;6:28345).

[0058] In particular, said medium is compatible with oral administration.

[0059] A composition as described may be a nutritional composition.

[0060] For example, a sports subject in whom it is necessary to maintain or increase muscle mass does not present any pathology and only requires a nutritional intake. According to another example, the composition according to the present description may be a nutritional composition intended for malnourished elderly people, for overweight people, malnourished for example due to the practice of a diet.

[0061] The present description also relates to a pharmaceutical composition comprising a bacterial strain of the species L. mucosae, or a lysate or a culture supernatant thereof, which is intended for subjects presenting, or likely to present, a pathology on which said composition has a prophylactic or therapeutic effect. By way of example, a composition according to the present description consists of a pharmaceutical composition when it is intended to prevent or treat a deregulation of insulin sensitivity and / or glycemia, as in the case of diabetes or prediabetes.

[0062] However, unless specifically stated, a composition comprising a bacterial strain of the species L. mucosae does not differ in its general characteristics set out in the description, depending on whether it is a nutritional composition or a therapeutic composition. Thus, essentially, a pharmaceutical composition is distinguished from a nutritional composition by the fact that the pharmaceutical composition has, in the subject to whom it is administered, a preventive effect and / or a treatment effect for a disease. Each of these compositions also complies with regulations specific to it and are distinguished by their mode of action. Indeed, pharmaceutical compositions exert a “pharmacological, immunological or metabolic action”; whereas nutritional compositions have a “nutritional or physiological” effect.

[0063] In certain embodiments of a composition according to the disclosure, the bacterial strain of the species L. mucosae is used as the only bacterial strain present in the composition.

[0064] In certain other embodiments of a composition according to the disclosure, the bacterial strain of the species Z. mucosae is combined with bacteria of one or more other probiotic bacterial strains, including commensal probiotic bacterial strains.

[0065] Non-limiting examples of probiotics include strains of bacteria belonging to the following genera: Bifidobacterium, Lactobacillus, Lactococcus, Enterococcus, Streptococcus, Kluyveromyces, Saccharomyces, Candida, Blautia, Faecalibacterium, Akkermansia, and combinations thereof.

[0066] Probiotics can be chosen from the group consisting of the following bacterial species: Bifidobacterium longum, Bifidobacterium lactis, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium adolescentis, Lactobacillus acidophilus, Lactobacillus casei (now Lacticaseibacillus casei), Lactobacillus paracasei (now Lacticaseibacillus paracasei), Lactobacillus salivarius (now Ligilactobacillus salivarius), Lactobacillus lactis (now Lactobacillus delbrueckii subsp. Lactis), Lactobacillus rhamnosus (now Lacticaseibacillus rhamnosus), Lactobacillus johnsonii, Lactobacillus plantarum (now Lactiplantibacillus plantarum subsp. Plantarum), Lactococcus lactis, Enterococcus faecium, Enterococcus faecalis, Saccharomyces cerevisiae, Saccharomyces boulardii, Akkermansia muciniphila, Blautia faecis, Faecalibacteium prausnitzii, Streptococcus thermophilus or their mixtures. According to a particular embodiment,a composition as described further comprises one or more other probiotic bacterial strains, in particular selected from the species Bifidobacterium longum, Bifidobacterium lactis, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium adolescentis, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus salivarius, Lactobacillus johnsonii, Lactobacillus salivarius, Lactococcus lactis, Enterococcus faecium, Enterococcus faecalis, Saccharomyces cerevisiae, Saccharomyces boulardii, Faecalibacterium prausnitzii, Akkermansia muciniphila, Blautia faecis, Streptococcus Thermophilus or mixtures thereof, preferably selected from the group consisting of Bifidobacterium longum NCC3001 (ATCC BAA-999), Bifidobacterium longum NCC2705 (CNCM 1-2618- cited in CA2761573 Al), Bifidobacterium longum NCC490 (CNCM 1-2170 - cited in W02006037922 Al), Bifidobacterium lactis NCC2818 (CNCM 1-3446 - cited in W02008116916 Al), Bifidobacterium breve strain HAS,Lactobacillus johnsonii NCC533 (CNCM 1-1225 - cited in WO2017060468), Enterococcus faecium SF 68 (NCC2768; NCIMB10415), Lactobacillus casei (CNCM 1-5662 and CNCM 1-5663 - cited in Giron et al., Front Nutr. 2022; 9: 928798, Published online 2022 Aug 10), Streptococcus thermophilus (CNCM 1-5334 - cited in EP3826655 Bl) and combinations thereof.,

[0067] In a particular embodiment, the composition is free of any other bacteria of the Lactobacillus species.

[0068] In some embodiments, the composition also comprises one or more prebiotics. The term "prebiotic" is used in its conventional sense in the prior art. Prebiotics consist of dietary substances that promote the growth of probiotic bacteria, including bacteria comprised in the microbiota.

[0069] Non-limiting examples of prebiotics include: oligosaccharides optionally containing fructose, galactose, mannose; dietary fiber, particularly fermentable fiber, soy fiber; inulin; human milk oligosaccharides (HMOs); polyphenols; chicory, mucus, and combinations thereof. Preferred prebiotics are fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), isomalto-oligosaccharides (IMO), xylo-oligosaccharides (XOS), arabino-xylo-oligosaccharides (AXOS), mannan-oligosaccharides (MOS), soy oligosaccharides, glycosyl sucrose (GS), lactosucrose (LS), lactulose (LA), palatinose-oligosaccharides (PAO), malto-oligosaccharides, resistant starches, gums and / or hydrolysates thereof, pectins and / or hydrolysates thereof, or combinations thereof.

[0070] Prebiotics can also include peptides, proteins, and complex secretions of peptides, sugars, and sulfur, such as mucus (e.g., intestinal mucus). In pigs, a positive effect of mannan oligosaccharides and L. mucosae has been tested (PMID: 34879142; J Anim Sci. 2021 Dec 1;99(12)). A high-fiber diet has also been shown to induce the culture of L. mucosae (Lactobacillus Mucosae Strain Promoted by a High-Fiber Diet Microorganisms. 2020 Aug 12;8(8):1225. PMID: 32806628)

[0071] In some embodiments, the composition comprises the combination of a probiotic and a prebiotic, which is then called a "symbiotic." The term "symbiotic" is used in its conventional sense in the prior art. The purpose of symbiotics is to improve the survival of the probiotic and increase its biological properties.

[0072] Non-limiting examples of symbiotics include the association bifidobacteria / fructo-oligosaccharides, lactobacilli / lactilol or even bididobacteria / galacto-oligosaccharides.

[0073] In some embodiments, the composition further comprises one or more vitamins. The vitamins may be folic acid, vitamin B 12 and vitamin B6, particularly folic acid and vitamin B 12, more particularly folic acid. In some embodiments, the composition comprises one or more vitamins that are fat-soluble, for example one or more of vitamin A, vitamin D, vitamin E and vitamin K or water-soluble, such as vitamin C.

[0074] In some embodiments, the composition comprises one or more polyphenols, such as flavanols, flavanones, flavonols, hydroxy cinnamic acids, and anthocyanins.

[0075] In some embodiments, the composition further comprises one or more minerals. The minerals may be selected from sodium, potassium, chloride, calcium, phosphate, magnesium, iron, zinc, copper, selenium, manganese, fluorine, iodine, chromium, or molybdenum. The minerals are generally added in salt form. The minerals may be added alone or in combination. In some embodiments, a composition according to the present disclosure generally comprises carriers or vehicles. "Carriers" or "vehicles" refer to materials suitable for administration and include any material known in the art, such as, for example, any liquid, gel, solvent, liquid diluent, solubilizing agent, or the like, which is non-toxic and does not interact with the components of the composition in a deleterious manner.Examples of nutritionally acceptable carriers include, for example, water, saline solutions, alcohols, silicones, waxes, petrolatum, vegetable oils, polyethylene glycols, propylene glycol, liposomes, sugars, gelatin, lactose, amylose, magnesium stearate, talc, surfactants, silicic acid, viscous paraffin, fragrance oil, monoglycerides and diglycerides of fatty acids, petroleum fatty acid esters, hydroxymethylcellulose, polyvinylpyrrolidone, etc.

[0076] In some embodiments, the composition further comprises any other ingredient or excipient known to be employed in the type of composition in question. Non-limiting examples of such ingredients include: proteins, amino acids, carbohydrates, oligosaccharides, lipids, nucleotides, nucleosides, other vitamins, minerals, bacterial metabolites, bioactive molecules and other micronutrients.

[0077] For example, a bacterial strain according to the invention can be combined with proteins in order to limit muscle wasting in the subject to whom it is administered.

[0078] According to another example, a bacterial strain according to the invention can be combined with n-3 polyunsaturated fatty acids in order to increase the insulin sensitivity of the subjects.

[0079] In some embodiments, the composition contains a carbohydrate source, for example in the form of prebiotics, or prebiotics when present in the composition. Any carbohydrate source commonly found in infant formulas, such as lactose, sucrose, maltodextrin, starch, and mixtures thereof, may be used, although the preferred carbohydrate source is lactose.

[0080] In some embodiments, a composition according to the present disclosure consists of a nutritional composition. In some embodiments, the nutritional composition is selected from complete food compositions, food supplements, nutraceutical compositions, and the like. The composition of the present disclosure may be used as a food ingredient and / or an animal feed ingredient. The food ingredient may be in the form of a solution or a solid, depending on the use and / or the mode of application and / or the mode of administration. As used herein, the term "food" refers to liquid (i.e., beverages), solid, or semi-solid dietary compositions, particularly total food compositions (food replacements), which do not require additional nutrient intake, or food supplement compositions.Dietary supplement compositions do not completely replace the supply of nutrients by other means. As used in this specification, the term "dietary ingredient" encompasses a formulation that is or may be added to functional foods or foodstuffs as a dietary supplement. "Nutritional food" or "nutraceutical" or "functional" means a food material that contains ingredients that have beneficial effects on health or are capable of improving physiological functions. "Dietary supplement" means a food material intended to supplement a normal diet. A dietary supplement is a concentrated source of nutrients or other substances that have a nutritional or physiological effect, when taken alone or in combination in small amounts.According to this description, "functional food" is used to designate food materials and corresponding products which are given importance not only because of their nutritional and taste value but also because of the presence of ingredients having beneficial physiological effects.

[0081] In some embodiments, the composition is a fermented dairy product or a milk-based product, which is preferably administered or ingested orally one or more times per day. Fermented dairy products include milk-based products, such as (but not limited to) desserts, yogurts, yogurt drinks, cottage cheese, kefir, fermented milk drinks, buttermilk, cheeses, salad dressings, low-fat spreads, cream cheese, soy-based drinks, ice cream, etc. In some embodiments, the composition is a fermented product based on plant matrices.

[0082] Alternatively, in some embodiments, the nutritional and / or nutritional supplement compositions may be non-dairy or unfermented dairy products. Unfermented dairy products may include ice cream, nutrition bars and seasonings, and the like. Non-dairy products may include powdered beverages and nutrition bars, etc. The products may be made using known methods, such as adding an effective amount of a bacterial strain of the species L. mucosae, or a combination of bacteria including the bacterial strain of the species L. mucosae, to a food base, such as skim milk or milk or a milk-based composition, and carrying out fermentation according to any known technique.In some embodiments, the composition is a beverage that may be a functional beverage or a therapeutic beverage, a thirst quencher, or a conventional beverage. For example, the composition of the present disclosure may be used as an ingredient for soft drinks, a fruit juice or a beverage comprising whey protein, teas, cocoa beverages, milk beverages, yogurts including drinking yogurts, cheeses, ice creams, popsicles and desserts, confectionery, cookies, cakes and cake mixes, snacks, balanced foods and beverages, frostings, acidified soy / juice beverage, aseptic / prepared chocolate beverage, bar mixes, powdered beverage mixes, calcium-fortified soy milk and chocolate, calcium-fortified coffee beverage.

[0083] In some embodiments, the composition comprises any other ingredient or excipient known to be employed in the type of composition in question. Non-limiting examples of such ingredients include: proteins, amino acids, carbohydrates, oligosaccharides, lipids, prebiotics or probiotics, nucleotides, nucleosides, other vitamins, minerals and other micronutrients.

[0084] In certain other embodiments, bacterial strains of the species L. mucosae, optionally in combination with probiotic bacteria of one or more other strains, are administered to the subject in the form of a pharmaceutical composition, which could correspond to a Live Biotherapeutic product (LBP) reference: Front Med (Lausanne) Rouanet et al2020 Jun 19;7:237. doi: 10.3389 / fmed.2020.00237 . For example, the bacteria of interest can be combined with pharmaceutically acceptable excipients, and optionally sustained-release matrices, such as biodegradable polymers, to form therapeutic compositions. The terms "pharmaceutically" or "pharmaceutically acceptable" refer to molecular entities and compositions that do not produce an adverse reaction, allergic reaction, or the like when administered to a mammal, in particular a human, as the case may be.A pharmaceutically acceptable carrier or excipient means a non-toxic, solid, semi-solid or liquid filler, diluent, encapsulating material or formulation aid of any type. In the pharmaceutical compositions of the present disclosure for oral, sublingual, subcutaneous, intramuscular, intravenous, transdermal, local or rectal administration, the active ingredient or combination of active ingredients may be administered in unit dosage form, in admixture with conventional pharmaceutical carriers, to animals and humans.Suitable unit dosage forms include oral dosage forms such as tablets, gel capsules, powders, granules and oral suspensions or solutions, sublingual and buccal dosage forms, aerosols, implants, subcutaneous, transdermal, topical, intraperitoneal, intramuscular, intravenous, subcutaneous, transdermal, intrathecal and intranasal dosage forms and rectal dosage forms. Typically, the pharmaceutical compositions contain carriers that are pharmaceutically acceptable for an injectable formulation.These may include, in particular, sterile isotonic saline solutions (monosodium or disodium phosphate, sodium, potassium, calcium or magnesium chloride and the like, or mixtures of these salts), or dry compositions, in particular lyophilized compositions, which, by the addition, as the case may be, of sterilized water or physiological saline, allow the constitution of injectable solutions. Pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions; formulations comprising sesame oil, peanut oil or aqueous propylene glycol; and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In all cases, the form must be sterile and must be fluid to the point of being easily squeezed.The pharmaceutical composition must be stable under the conditions of manufacture and storage and must be preserved from the contaminating action of microorganisms, such as bacteria and fungi. Solutions comprising the compounds of the disclosure in free base form or as pharmacologically acceptable salts may be prepared in water suitably mixed with a surfactant, such as hydroxypropylcellulose. Dispersions may also be prepared in glycerol, liquid polyethylene glycols and mixtures thereof, as well as in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms. The at least one bacterial strain of the species L. mucosae according to the present disclosure may be formulated into a composition in a neutral form or in a salt form.Pharmaceutically acceptable salts include acid addition salts (formed with the free amino groups of the protein) and which are formed with inorganic acids such as, for example, hydrochloric or phosphoric acids, or organic acids such as acetic, oxalic, tartaric, mandelic, and the like. Salts formed with free carboxyl groups may also be derived from inorganic bases such as, for example, sodium, potassium, ammonium, calcium, or ferric hydroxides, and from organic bases such as isopropylamine, trimethylamine, histidine, procaine, and the like.

[0085] According to a particular embodiment, a bacterial strain according to the invention is included in an oral composition, and more particularly in an oral composition chosen from the group consisting of a food product, a drink, a pharmaceutical product, a nutraceutical, a food additive, a food supplement, a dairy product and a living biotherapy product (LBPs).

[0086] As used herein, the term "therapeutically effective amount" is an equivalent expression that refers to the amount of a therapy (e.g., a prophylactic or therapeutic agent), which is sufficient to reduce the severity and / or duration of a disease, ameliorate one or more of its symptoms, prevent the progression of a disease or cause the regression of a disease, or which is sufficient to result in the prevention of the development, recurrence, onset or progression of a disease or one or more of its symptoms, or to enhance or improve the prophylactic and / or therapeutic effect(s) of another therapy (e.g., another therapeutic agent) useful for treating a disease. Typically, in a pharmaceutical composition according to the present description, the bacterial strains of the species L.mucosae are present in a quantity sufficient to induce a reduction in insulin resistance in the subject being treated. The measurement of insulin resistance in a subject can be carried out using any technique known to those skilled in the art. Preferably, the measurement of insulin resistance in a subject is carried out by calculating the HOMA IR index, as illustrated in the examples. The HOMA IR method (for "HomeOstasis Model Assessment for Insulin Resistance"), which was developed from the mathematical modeling of the quantitative responses of the main organs of glucose metabolism. The value of the HOMA IR index is obtained using a plasma insulin or C-peptide value and fasting blood glucose (Sheen, 2007, Therapy, Vol. 62: 311-318).The occurrence and / or level of insulin resistance can also be established by measuring fasting blood glucose, by measuring fasting insulin levels or by the OGTT test (for "Oral Glucose Tolerance Test", or "hyperglycemia challenge test" - See for example, "Measurement of insulin resistance and glucose tolerance", 2006, Haute Autorité de Santé (HAS), France).

[0087] In a composition according to the description, whether it is a nutritional or food composition, where appropriate a food supplement, or whether it is a pharmaceutical composition, the bacteria or bacteria may be in various forms, for example in liquid form or in powder form. The bacteria or bacteria may be in lyophilized form.

[0088] The quantity of bacteria of the species L. mucosae which is provided to the subject may be variable, depending on the physiological state of said subject, and in particular depending on the level of imbalance in nutrient intake compared to the nutrient requirements of said subject. The quantity of bacteria of the species L. mucosae which must be provided to said subject may be easily adapted by a person skilled in the art.

[0089] In preferred embodiments, whether the composition is a nutritional composition or a pharmaceutical composition, the composition comprises an amount of bacteria of the species L. mucosae that is suitable for a daily intake, preferably a daily oral intake, of at least 10 3 colony forming units (or "CFU"). In these preferred embodiments, the daily intake, in particular the daily oral intake, of bacteria of the species L. mucosae is at most 10 13colony forming units (or “CFU”).

[0090] In embodiments wherein the composition further comprises other probiotic bacteria, the amount of these probiotic bacteria is determined by a person skilled in the art based on his general knowledge. The amount of these other probiotic bacteria may vary from 10 3 at 10 13 other probiotic bacteria.

[0091] In some embodiments, a composition according to the present disclosure generally comprises carriers or vehicles. "Carriers" or "vehicles" refer to materials suitable for administration and include any material known in the art, such as, for example, any liquid, gel, solvent, liquid diluent, solubilizing agent, or the like, which is non-toxic and does not interact with the components of the composition in a deleterious manner.Examples of nutritionally acceptable carriers include, for example, water, saline solutions, alcohols, silicones, waxes, petrolatum, vegetable oils, polyethylene glycols, propylene glycol, liposomes, sugars, gelatin, lactose, amylose, magnesium stearate, talc, surfactants, silicic acid, viscous paraffin, fragrance oil, monoglycerides and diglycerides of fatty acids, petroleum fatty acid esters, hydroxymethylcellulose, polyvinylpyrrolidone, etc.

[0092] In other embodiments of a composition according to the present description, said composition is in the form of a pharmaceutical composition comprising one or more pharmaceutically acceptable excipients.

[0093] Such a pharmaceutical composition may be presented in the form of a package comprising a plurality of dosage units.

[0094] The term "dosage unit" is used in its conventional sense in pharmacy (e.g. a pill, a capsule, a tablet, the contents of an ampoule, etc.).

[0095] Uses

[0096] GLP-1 is a peptide that has numerous metabolic effects in the host, in particular, it improves the secretion of insulin by the pancreas, promotes glucose tolerance and therefore optimizes the energy and nitrogen metabolisms of the host. The inventors have surprisingly shown that bacteria of the Limosilactobacillus mucosae type make it possible to increase the production of GLP-1 in vitro, and thus to prevent or limit the metabolic effects of pathologies or conditions linked to a deficit in the action of GLP-1: state of insulin resistance (for example type II diabetes), metabolic diseases, difficulty in regulating food intake, regulation of transit disorders, etc.

[0097] As will appear in the description, a bacterial strain of the species L. mucosae according to the invention or a composition comprising it are mainly intended to prevent and / or treat:

[0098] (i) a disorder related to deregulation of insulin sensitivity and / or blood sugar, or

[0099] (ii) loss of muscle mass and / or muscle function.

[0100] According to a particular embodiment, the loss of muscle mass and / or muscle function is linked to insulin resistance.

[0101] These disorders are linked to a deficit in the action of GLP-1.

[0102] A bacterial strain of the species L. mucosae according to the invention or a composition comprising it may in particular be useful in the prevention and / or treatment of disorders linked to transit or disorders of appetite regulation.

[0103] According to a particular embodiment, the bacterial strain is included in a composition comprising a physiologically acceptable medium, as defined above.

[0104] In the context of the present description, the term "prevent" or "prevention" means reducing to a lesser degree the risk or probability of occurrence of a given phenomenon, i.e., in the present invention, disorders requiring an increase in the level of GLP-1.

[0105] As used herein, "treat" or "treatment" means the alleviation or mitigation of pathological processes, or the alleviation or mitigation of one or more symptoms related to a pathological process, and in particular to one of the disorders described in the application requiring an increase in the level of GLP-1. This description relates to the nutritional uses and therapeutic uses of a bacterial strain or composition as defined in this application.

[0106] The compositional features, including nutritional composition and therapeutic composition, including various embodiments, are described in detail herein, including the amounts of active ingredient(s), especially the amounts of bacteria of the species L. mucosae included in these compositions.

[0107] (i) Disorders related to deregulation of insulin sensitivity and / or blood glucose

[0108] Dysregulation of insulin sensitivity, such as the development of insulin resistance, describes a situation where liver, muscle, and fat cells, for example, become resistant to insulin. Less glucose then enters these cells, and it remains in the blood. In response to insulin resistance, insulin-secreting pancreatic cells tend to produce more of it (hyperinsulinemia) and may eventually become exhausted. Insulin production then becomes insufficient and blood glucose levels become too high (hyperglycemia). Insulin resistance can also affect other insulin-regulated metabolisms, such as protein metabolism. Insulin, combined with meals, is a major stimulator of muscle protein anabolism.Insulin resistance therefore contributes to muscle wasting due to a lack of anabolism in the muscle, particularly during mealtimes.

[0109] Blood glucose regulation is the process by which blood glucose levels, known as glycemia, are kept close to a value that is beneficial to the body. This regulation is part of the processes that maintain homeostasis within the body. Normal fasting blood glucose levels in humans are statistically between 0.70 and 1.10 g / L. When blood glucose levels are abnormally higher or lower than this threshold, this is called dysregulation.

[0110] The main disorders related to deregulation of insulin sensitivity and / or blood sugar according to this text are prediabetes, type 1 diabetes and type 2 diabetes. They can be caused by obesity or not. However, the activation of receptors expressed at the level of insulin cells (P) and certain peripheral tissues by GLP-1 stimulates insulin secretion (insulinotropic effect) but also activates the transcription of the insulin gene and increases insulin biosynthesis and inhibits the release of glucagon (static glucagon effect).

[0111] The term "prediabetes" refers to a pathophysiological condition characterized, in particular, by elevated blood glucose levels compared to normal, but below the threshold for defining type 2 diabetes. Fasting blood glucose levels are considered to be (i) normal between 0.70 and 1.10 g / l, (ii) a sign of prediabetes between 1.10 and 1.25 g / l and (iii) a sign of diabetes when > 1.25 g / l. Prediabetes generally does not induce symptoms, but is often associated with obesity, dyslipidemia, and hypertension. It is a risk factor for cardiovascular disease. Prediabetes is characterized, in particular, by glucose intolerance. Stimulation of insulin and glucagon secretion by the pancreas by GLP1 controls glycemic excursions by reducing fasting blood glucose. GLP1 induces glucose uptake and hepatic storage and inhibits gluconeogenesis.Furthermore, and in addition to increasing insulin secretion, GLP1 also plays a role in improving insulin sensitivity in many tissues, including muscle (Muller et al., 2019, Mol Metab).

[0112] Type 1 diabetes or TID refers to a chronic condition characterized by a complete lack of insulin production. A person living with type 1 diabetes therefore relies on daily insulin injections or an insulin pump to survive. As explained above for prediabetes, GLP1 plays many roles in blood sugar control, including controlling the stimulation of insulin and glucagon secretion, glucose uptake and hepatic storage, inhibition of gluconeogenesis, and improving the insulin sensitivity of many tissues.

[0113] Type 2 diabetes or T2D is a chronic disease that occurs when the pancreas does not produce enough insulin (a hormone that regulates blood sugar), or when the body is unable to effectively use the insulin it produces.

[0114] According to a particular embodiment, the disorder linked to the deregulation of blood sugar is type 2 diabetes. (ii) Loss of muscle mass and / or muscle function

[0115] According to a particular embodiment, the disorder to be prevented and / or treated is a loss of muscle mass and / or function, characterized in that the subject in need thereof is chosen from elderly subjects affected by sarcopenia, overweight subjects and obese subjects affected by sarcopenic obesity and subjected to a diet, subjects affected by cachexia, in particular linked to cancer, inflammatory bowel disease or chronic obstructive pulmonary disease, immobilized subjects, diabetic or prediabetic subjects, “major burn” subjects, septic subjects or those having suffered a viral infection, convalescing and / or immobilized subjects, and subjects having undergone intestinal resection or presenting intestinal malabsorption.

[0116] Subjects who have lost muscle mass in the above-mentioned conditions are generally resistant to the anabolic action of the meal and / or the action of insulin. While subjects experiencing significant muscle wasting are often insulin resistant, not all insulin-resistant or prediabetic subjects are necessarily experiencing muscle wasting, a phenomenon that can develop gradually over time, with muscle wasting and the development of insulin resistance strongly metabolically linked (Daily and Park, 2022 Cells - DOI: 10.3390 / cells 11030338)

[0117] Indeed, it is known that GLP-1 has advantageous properties that optimize the energy use of nutrients and limit muscle wasting (Hong et al., Journal of Cachexia, Sarcopenia and Muscle 2019; 10: 903-918), particularly in insulin-resistant individuals (Massimo et al., The Impact of Glucose-Lowering Drugs on Sarcopenia in Type 2 Diabetes: Current Evidence and Underlying Mechanisms. Cells 2021, 10, 1958).

[0118] Muscle mass loss can be measured by various technologies known to those skilled in the art, such as arm circumference, bioelectrical impedance, bioenergetic X-ray tabsorptiometry (DXA), and computed tomography (Mareschal et al, 2019 Journal of Clinical Medicine, doi: 10.3390 / jcm8071040).

[0119] The loss of muscle function (strength, power, physical performance) can be measured by different technologies known to those skilled in the art such as the grip test (grip test using a dynamometer), 6-minute walking speed, 30-second chair stand test (chair stand), SPPB (Short Physical Performance Battery) test which combines walking speed, balance, chair stand), the “time to get up and go” test (consists of getting up from a chair, walking 3 meters, turning around and sitting down again) (Beaudart et al 2019, Calcified Tissue International, doi: 0.1007 / s00223-019-00545-w ).

[0120] For the purposes of this description, the term "elderly subject" means a human subject or a non-human mammalian subject, including a pet such as a dog or a cat, which shows signs of senescence such as impaired metabolic functions (e.g. absorption, digestion, excretion, dysfunction of tissues and organs), locomotor difficulties and reduced resistance to external aggressions. The term "elderly subject" or "elderly person", in relation to a human, means a subject aged 65 years or older. The term "elderly subject", in relation to a canine, in particular a dog, means a subject aged (i) over 12 years for a canine, in particular a dog, of small size or (ii) over 9 years for a canine, in particular a dog, of medium size, or (iii) over 7 years for a canine, in particular a dog, of large size. By "elderly subject", in relation to a feline, in particular a cat, we mean a subject over 13 years old.

[0121] Sarcopenia (a word derived from Greek that can be translated as "lack of flesh"), initially defined by a loss of skeletal muscle mass, is currently characterized by a loss of muscle mass associated with functional deterioration (European Working Group on Sarcopenia in Older People (EWGSOP) - Cruz Jentoft et al, 2019 Age and Aging). After developing until the age of 20 to 30, muscle mass decreases by approximately 1% per year, even in healthy people. This process accelerates between the ages of 50 and 60. Sarcopenia affects physical performance, promotes gait disorders and is a factor in frailty and an increased risk of dependency, particularly in the elderly.Note that sarcopenia does not only affect the elderly but also insulin-resistant populations such as obese people; this is known as sarcopenic obesity (Working Group from European Society for Clinical Nutrition and Metabolism (ESPEN) and European Association for the Study of Obesity (EASO) - Donini et al, 2022, Obesity Facts). This muscle wasting can also occur over shorter time steps, particularly in intense catabolic situations such as cancers and associated powerful treatments such as chemotherapy. In this case, we rather speak of cachexia (see below). Sarcopenia is associated with an increased risk of falls and fractures leading to immobilization which, in turn, aggravates sarcopenia. We are thus witnessing a "snowball" effect amplifying the loss of muscle mass and function linked to age.

[0122] Obesity is a pathophysiological condition in which an individual exhibits, in particular, weight gain and excess adipose tissue, generally induced by an obesogenic diet, including, in particular, excessive consumption of high-calorie foods, genetic predispositions or insufficient or non-existent exercise. An individual declared obese has a body mass index (BMI) greater than 30. The body mass index, according to an official definition of the World Health Organization (WHO), is the indicator of health risks associated with excessive and underweight weight. BMI is calculated by dividing the individual's weight (in kilograms) by their height (in meters) squared. A BMI value is associated with a specific body type according to the classification given by the WHO.

[0123] Unlike an "obese" individual, an "overweight individual" is defined as an individual whose condition is not pathophysiological. An overweight individual often also has excess adipose tissue. An individual is generally considered overweight when they have a body mass index (BMI) between 25 and 30.

[0124] Sarcopenic obesity occurs when an individual has both excess body fat and reduced lean muscle mass. This clinical condition most often affects older adults.

[0125] "Cachexia," a profound weakening of the body, is characterized in particular by the loss of adipose tissue and muscles. It is common in many diseases, including cancers that are difficult, if not impossible, to control or cure and, as mentioned above, occurs over much shorter periods (days to weeks). Cancers, particularly those of the pancreas and stomach, cause severe cachexia. Patients can lose 10 to 20% of their body mass. Cachexia can also be linked to other catabolic pathologies such as inflammatory bowel disease or chronic obstructive pulmonary disease, a viral infection, or sepsis.

[0126] It has been shown that decreased mobility is associated with a decrease in muscle mass index and muscle strength. This is also true conversely, as reduced mobility and physical activity in the broadest sense can aggravate or generate the onset of sarcopenia. Immobilized subjects are therefore likely to develop a loss of muscle mass and / or function. In the context of this text, this may include subjects convalescing and / or immobilized after a fall.

[0127] So-called "severe burn victims", as in the case of pathologies inducing hypermetabolism (sepsis, viral attack, or even cancer), are characterized by significant macro and micronutrient requirements to meet the increased needs linked to the pathology, in particular due to the healing process (for "severe burn victims") and the inflammatory response (Knuth et al 2021, American Journal of Physiology. Cell Physiology). Furthermore, due to high inflammation, there is generally the establishment of resistance to the anabolic effect of the meal and insulin resistance mentioned above as a determining factor in obesity and sarcopenia in elderly subjects.

[0128] In subjects with intestinal malabsorption, or who have undergone intestinal resection, GLP-1 can help optimize nutrient utilization. Indeed, patients who have undergone intestinal resection have been found to have increased production of GLP1 (Jeppesen et al 2000, Gut; Gillard et al 2017, Front Physiol), allowing intestinal motility to be adapted and host metabolism to be optimized to the lower intake of nitrogenous and energy nutrients. The repercussions will be particularly notable on the subjects' energy (fat mass) and nitrogen (lean mass and muscle mass) stores. An improvement in the intestinal secretion of GLP-1 by these patients, particularly through the intake of a GLP-1 secreting probiotic, is therefore beneficial in these subjects.

[0129] According to a particular embodiment, the subject to be treated, otherwise called a subject in need thereof, is a subject having an indication for administration based on GLP-1 receptor agonists. An individual having an indication for administration based on GLP-1 receptor agonists is an individual suffering from a disorder or disease which can be treated or the symptoms of which can be alleviated by administering to said individual one or more GLP-1 receptor agonists.

[0130] GLP-1 receptor agonists are most often synthetic peptides whose polypeptide sequence is close to that of GLP-1 and which act by binding to GLP-1 receptors, generally with increased stability compared to endogenous GLP-1.

[0131] Examples of GLP-1 receptor agonists include exenatide, liraglutide, dulaglutide, semaglutide, tirzepatide, lixisenatide, albiglutide, exenatide QW, BI 456906 mazdutide (IBI362; LY3305677), retatrutide (LY3437943), danuglipron, exendin-4, or cotadutide.

[0132] According to a particular embodiment, the subject having an indication for an administration based on GLP-1 receptor agonists is chosen from the list consisting of insulin-resistant subjects such as diabetic subjects, overweight subjects, in particular obese subjects, subjects having undergone metabolic surgery, subjects seeking to regulate their appetite, subjects suffering from liver diseases, subjects suffering from cardiovascular pathologies, in particular suffering from cardiovascular pathologies linked to diabetes, subjects suffering from inflammation linked to diabetes and / or a metabolic syndrome, subjects affected by sarcopenia, subjects affected by cachexia; and subjects suffering from neurodegenerative diseases.

[0133] Metabolic surgery refers to a type of surgery that aims to treat metabolic disease using surgical methods. Metabolic surgery, also known as diabetes or sugar surgery, includes surgical procedures that control both diabetes and obesity. These may include surgeries that allow for appetite regulation, gastric emptying, food preference, and / or taste.

[0134] Liver diseases for which GLP-1 agonist-based administration may be indicated include, for example, non-alcoholic steatohepatitis (NASH).

[0135] Cardiovascular pathologies for which administration based on GLP-1 agonists may be indicated include atherosclerosis, myocardial infarction, stroke, or alteration of the lipid profile (total cholesterol, LDL cholesterol, HDL / LDL ratio).

[0136] Neurodegenerative diseases for which administration of GLP-1 agonists may be indicated include Alzheimer's disease or Parkinson's disease.

[0137] According to a particular embodiment, the subject to be prevented and / or treated is chosen from elderly subjects affected by sarcopenia, overweight subjects and obese subjects affected by sarcopenic obesity and subjected to a diet. The description also describes a method for preventing and / or treating disorders requiring an increase in the level of GLP-1 in a subject in need thereof, said use being chosen from (i) the prevention or treatment of a disorder linked to a deregulation of insulin resistance and / or glycemia and (ii) the prevention or treatment of loss of muscle mass and / or muscle function, characterized in that it comprises at least one step of administering a bacterial strain of the species Limosilactobacillus mucosae.

[0138] Furthermore, the invention relates to the non-therapeutic use of a bacterial strain of the species L. mucosae according to the invention or of a composition comprising it for maintaining or increasing muscle mass and / or function in a subject in need thereof, in particular in a subject selected from a malnourished subject, an elderly subject, in particular a malnourished elderly subject, and a subject engaging in intense physical exercise.

[0139] For the purposes of this description, "malnourished" means a "state of an organism in nutritional imbalance" (See, "Diagnosis of malnutrition in children and adults - Method Recommendations for clinical practice", November 2019, Haute Autorité de Santé and Fédération Française de Nutrition), said imbalance being characterized by a negative energy and / or protein balance. This definition encompasses a plurality of situations that can lead to a state of malnutrition, such as an isolated deficit in nutrient intake, an increase in expenditure or losses leading to an imbalance. This term also covers subjects with exacerbated nutritional needs.The imbalance inherent in malnutrition leads to deleterious effects on the body, accompanied by measurable changes in body functions and / or body composition, these changes being able to be associated with a worsening of the course of diseases from which the subject may be affected.

[0140] “Elderly subjects” are defined above.

[0141] "Intense physical exercise" means physical activity requiring significant effort that results in decreased breathing and increased heart rate. Intense physical activity is characterized by a MET (Metabolic Equivalent of Task - 1 MET corresponds to the oxygen intake of 3.5 mL per kilogram of body weight per minute) greater than 6. The MET evaluates the ratio between energy consumption during physical exercise and energy consumption at rest. During physical exercise, and particularly in insulin-resistant subjects, GLP-1 may be an interesting complementary strategy to help optimize blood glucose management and strengthen insulin sensitivity. Intense physical activity also leads to stimulation of GLP-1 production.

[0142] The present text also describes a method for maintaining or increasing muscle mass and / or function in a subject in need thereof, in particular in a subject selected from a malnourished subject, an elderly subject, in particular a malnourished elderly subject, and a subject engaging in intense physical exercise, comprising at least the step of administering to the subject in need thereof at least one bacterial strain of the species Limosilactobacillus mucosae.

[0143] Finally, the present invention relates to the strain of the species Limosilactobacillus mucosae deposited with the CNCM under accession number CNCM 1-5661.

[0144] The invention is described below in more detail by means of the following examples which are presented for the purpose of illustration.

[0145] Example

[0146] 1. Selection of bacterial strains capable of secreting GLP-1

[0147] Sixty-one Lactobacillus isolates from the feces of gnotobiotic animals previously transplanted with the feces of a patient with short bowel syndrome were tested. These lactobacilli have a strong tropism for the intestine, as these strains are abundant in the feces of patients with short bowel syndrome and are capable of colonizing the digestive tract of axenic rats.

[0148] The inventors carried out an initial morphological, phenotypic and genomic characterization by sequencing the 16S gene, and divided the isolates into 6 species and 1 to 2 isolates per species were selected, for a total of 7 strains.

[0149] The 6 species are:

[0150] Lacticaseibacillus casei (strain 1 and strain 2),

[0151] Lacticaseibacillus camelliae, (strain 3)

[0152] Ligilactobacillus salivarius, (strain 4)

[0153] Lacticaseibacillus rhamnosus. (strain 5) Limosilactobacillus reuteri, (strain 6)

[0154] Limosilactobacillus mucosae, (strain CNCM 1-5661, also called strain I-

[0155] 5661)

[0156] The strains were characterized by functional tests at INRAE ​​Aurillac (Aurillac Mixed Cheese Research Unit, UMR 0545).

[0157] All of the strains isolated above were incubated on SCT-1 mouse neuroendocrine intestinal cells. After incubation for 10 9 bacteria with 2xl0 6 SCT-1 cells at 80% confluence for 4 hours at 37°C and 5% CO2, the cell supernatant was recovered and a peptide, GLP-1, was measured (by ELISA method) in this supernatant.

[0158] The results are shown in Figure 1.

[0159] Of all the strains tested, none demonstrated significant synthesis of GLP-1 in the culture medium, except for strain CNCM 1-5661 which resulted in very significant production (P<0.05) of GLP-1 in the medium.

[0160] Indeed, among all strains from the same donor, only the Z. mucosae CNCM 1-5661 strain specifically increased GLP-1 production 25 times. When lactic acid bacteria of the species Lacticaseibacillus casei, which were isolated from the same patient, were incubated under the same conditions, no GLP-1 release was observed (results not shown here - see Example 4 and associated results below).

[0161] This strain corresponds to the species Limosilactobacillus mucosae.

[0162] The Control group corresponds to a culture of intestinal cells in a sterile medium (no production of GLP-1)

[0163] Results of induction of GLP-1 secretion by STC-L cells

[0164] STC-1 cells were obtained from an ATCC collection (Reference STC-1, CRL-3254™) and were cultured and prepared for co-incubation the day before the experiment. Bacteria that had been frozen in dry pellets were thawed on the day of the experiment and taken up in culture medium without FCS or antibiotics. They were prepared by serial dilution to respect the following MOI (Multiplicity of Infection): 1:10, 1:100 and 1:1000.

[0165] STC-1 cells were washed and then the medium containing the bacteria was added. After 4 hours of coculture, the supernatants were collected and counted. Then the supernatants were stored, as well as the cells at -80°C for the subsequent GLP-1 assay. The quantity of GLP-1 was determined by ELISA according to the instructions of the supplier Assay Genie (ELISA GLP-1 Mouse (ref: MOFI00854)).

[0166] GLP-1 production is expressed in pg / ml.

[0167] Definitions of terms used in Table 1 below are given here: Control: STC-1 cells in the presence of culture medium

[0168] ME: 10 (number of bacteria added for one STC-1 cell

[0169] C: Indicates that CNCM-I5661 bacteria were cultured in MRS medium (supplier BD, reference: 288130, reconstitution made according to the supplier's instructions), then centrifuged and frozen as dry pellets. The dry pellets were then resuspended in STC cell culture medium.

[0170] V: Indicates that CNCM-I5661 bacteria were cultured in “veganMRS” medium (supplier BIOKAR, reference: BK176HA, reconstitution made according to the supplier’s instructions), then centrifuged and frozen as dry pellets. The dry pellets were then resuspended in the STC-1 cell culture medium.

[0171] 61C-10: incubation of STC-1 cells in the presence of strain CNCM-I5661. MOI: 10 (10 times more bacteria than STC-1 cells)

[0172] 61C-100: incubation of STC-1 cells in the presence of strain CNCM-I5661. MOI: 100 (100 times more bacteria than STC-1 cells)

[0173] 61C-1000: incubation of STC-1 cells in the presence of strain CNCM-I5661. MOI: 1000 (1000 times more bacteria than STC-1 cells)

[0174] [Table 1]

[0175] The results shown in the table above indicate a dose effect of the strain and also show that the strain retains its functions even if it is grown in another medium.

[0176] Conclusion: The presence of the CNCM-5661 strain induces the production of the enterohormone GLP-1 by STC-1 cells. This production is all the more important as the number of bacteria increases. This production is not observed in the presence of strains of the species Lacticaseibacillus casei, which come from the same patient. The pro-GLP-1 effect of the CNCM 1-5661 strain is not dependent on the culture medium used for the culture of the strain.

[0177] Furthermore, the inventors showed that GLP-1 production increased as a function of contact time between bacteria of the CNCM 1-5661 strain and intestinal cells (see Figure 2).

[0178] 2- Capacity of the CNCM 1-5661 strain to survive in the intestinal environment

[0179] To determine whether the CNCM 1-5661 strain is capable of surviving in the intestinal environment, various tests were carried out.

[0180] Tolerance of the bacteria to gastric acidity (stomach) The bacteria were placed in an acidic environment (pH 2.5 and 3) for 45 and 90 minutes, corresponding to the average residence times of the food bolus in the stomach before passing into the duodenum.

[0181] The bacteria showed very good resistance to gastric medium (composition: HCl, pepsin, NaCl), with no significant difference between incubation times and the two pHs tested (p > 0.05, Fisher exact test).

[0182] The results are presented in Table 2 below.

[0183] [Table 2]

[0184] - Tolerance of the bacteria to gastric acidity (bile salts)

[0185] The inventors also tested the survival of the bacteria under conditions encountered downstream of the stomach that include the presence of bile salts. The survival of strain CNCM 1-5661 was therefore tested in the presence of bile salts after 1h, 2h, 3h and 4h of incubation at 37°C.

[0186] The bacteria showed very good resistance to bile salts, with no significant difference between incubation times (p > 0.05, Fisher exact test).

[0187] The results are presented in Table 3 below.

[0188] [Table 3]

[0189] 3- Capacity of the CNCM 1-5661 strain to adhere to intestinal cells

[0190] Finally, to estimate the probiotic potential of the CNCM 1-5661 strain, the inventors determined its ability to adhere to human Caco-2 intestinal cells. The determination of the viable number of lactic acid bacteria adhering to intestinal cells was carried out after 3 hours of contact with Caco-2 cells at an MOI (multiplicity of infection) value of 0.1, 1, 10 and 100.

[0191] Strain CNCM 1-5661 has a satisfactory and similar percentage of adherence to other microorganisms, without any significant difference between the MOIs tested (p>0.05, Fisher exact test).

[0192] The results are presented in Table 4 below. [Table 4]

[0193] 4- Extension of the properties described on the CNCM 1-5661 strain to the entire species Limosilactobacillus mucosae

[0194] The ability of other strains of the species Limosilactobacillus mucosae to enable GLP-1 secretion from SCT-1 cells in culture was tested on other strains of the species Limosilactobacillus mucosae to determine whether the beneficial effect observed on the strain L. mucosae CNCM 1-5661 is also applicable to other strains of the same species.

[0195] Three other strains were therefore tested: DSM 13345, DSM 13346, and DSM 102820. The strains CNCM 1-5661 (as a positive control) and a strain of L. Casei (negative control, which does not induce the synthesis of GLP-1) were also used:

[0196] Control: sterile cell medium;

[0197] L. casei strain (negative control) -5.10 9 CFU / mL (strain A);

[0198] L. mucosae CNCM 1-5661 (positive control) -5.10 9 CFU / mL (strain B);

[0199] - L. mucosae DSM 13345 (S32T) -2.10 9 CFU / mL (strain C);

[0200] L. mucosae DSM 13346 -4.10 9 CFU / mL (strain D);

[0201] L. mucosae DSM 102820 -5.10 9 CFU / mL (strain E);

[0202] In the “diluted” conditions, strains B to E were diluted 1 / 10 e The results, presented in Figure 3, show that in the presence of all strains of the species Limosilactobacillus mucosae tested, GLP-1 synthesis by SCT-1 cells was observed. Furthermore, this GLP-1 production is dose-dependent.

[0203] 5- Effect of the CNCM 1-5661 strain on muscle mass in a frail aged rat model

[0204] To estimate the anabolic probiotic effect on GLP-1 targets, the inventors measured the capacity of the strain L. mucosae CNCM 1-5661 according to the invention (shown to be capable of inducing the synthesis of GLP-1 by SCT-1 cells in culture) and of a strain of the species L. casei outside the invention (non-inducing GLP-1 production) on the muscle mass of a frail aged rat model.

[0205] The inventors carried out an in vivo study over a period of 1 month on aged rats (20 months) according to the following groups:

[0206] - ad libitum fed group (n= 15);

[0207] - group fed 75-80% ad libitum (to mimic malnutrition in the elderly, one of the factors of fragility) (n=16);

[0208] - group fed 75-80% of the ad libitum supplemented daily with the bacteria CNCM 1-5661 (10 9 CFU) (n=13); and

[0209] - group fed 75-80% of the ad libitum supplemented daily with a bacterium of the species Limosilactobacillus casei (10 9 CFU) (n=16).

[0210] The animals were sacrificed at the end of the experiment, weighed, and the hindlimb muscles (gastrocnemius, Extensor digitorum longus, Soleus, Tibialis anterior) were excised and weighed. The sum of the weights of these 4 muscles was calculated and reduced to the weight of the animals.

[0211] The results are presented in Figure 4 and show that only Z. mucosae CNCM-I5661 supplementation allowed restricted rats to increase their muscle mass relative to ad libitum-fed (P=0.01) and restricted (trend, P=0.092) animals.

[0212] Furthermore, muscle mass was similar in the AL, R, and R + L casei groups, suggesting that unlike L mucosae CNCM-I5661, L casei did not increase muscle mass. This suggests a specific effect of Lactobacillus L mucosae CNCMI-I5661 to increase muscle mass in the frail aged rodent model unlike other lactobacilli.

[0213] BUDAPEST TREATY ON THE INTERNATIONAL RECOGNITION OF THE DEPOSIT OF MICROORGANISMS FOR THE PURPOSES OF PATENT PROCEDURE

[0214] INTERNATIONAL FORMULA

Claims

Claims 1. Bacterial strain of the species Limosilactobacillus mucosae, or a lysate or culture supernatant thereof, for use in the prevention and / or treatment of disorders requiring an increase in the production of GLP-1 in a subject in need thereof, said disorders being chosen from (i) a disorder linked to a deregulation of insulin sensitivity and / or glycemia and (ii) loss of muscle mass and / or muscle function.

2. Bacterial strain for its use according to claim 1, characterized in that the subject in need thereof is a subject having an indication for administration based on GLP-1 receptor agonists.

3. Bacterial strain for its use according to claim 2, characterized in that the subject having an indication for an administration based on GLP-1 receptor agonists is chosen from the list consisting of insulin-resistant subjects such as diabetic subjects, overweight subjects, in particular obese subjects, subjects having undergone metabolic surgery, subjects seeking to regulate their appetite, subjects suffering from liver diseases, subjects suffering from cardiovascular pathologies, in particular suffering from cardiovascular pathologies linked to diabetes, subjects suffering from inflammation, in particular inflammation linked to diabetes and / or to a metabolic syndrome, subjects affected by sarcopenia, subjects affected by cachexia; and subjects suffering from neurodegenerative diseases.

4. Bacterial strain for use according to any one of claims 1 to 3, characterized in that the disorder is a disorder linked to a deregulation of insulin sensitivity and / or glycemia chosen from prediabetes, type 1 diabetes and type 2 diabetes.

5. Bacterial strain for use according to any one of claims 1 to 3, characterized in that the disorder is a loss of muscle mass and / or function and in that the subject in need thereof is chosen from elderly subjects affected by sarcopenia, overweight subjects and obese subjects affected by sarcopenic obesity and subjected to a diet, diabetic or prediabetic subjects, and / or subjects affected by cachexia, in particular linked to cancer, inflammatory bowel disease or chronic obstructive pulmonary disease, immobilization, a situation of “major burns”, septic or having suffered an infection viral, convalescence and / or immobilization, and / or intestinal resection or intestinal malabsorption.

6. Bacterial strain for use according to any one of claims 1 to 5, characterized in that the bacterial strain is chosen from the strain of the species L. mucosae deposited with the CNCM under accession number CNCM I-5661, the strain of the species L. mucosae deposited with the DSM under accession number DSM 13345, the strain of the species Z. mucosae deposited with the DSM under accession number DSM 13346, the strain of the species Z. mucosae deposited with the DSM under accession number DSM 102820, or a mixture thereof, and in particular is the strain of the species L. mucosae deposited with the CNCM under accession number CNCM 1-5661.

7. Bacterial strain for use according to any one of claims 1 to 6, characterized in that the bacteria of the species L. mucosae are in a living or dead form, preferably in a living form.

8. Bacterial strain for its use according to any one of claims 1 to 7, characterized in that the bacterial strain is included in a composition comprising a physiologically acceptable medium, in particular in an oral composition, and more particularly in an oral composition chosen from the group consisting of a food product, a drink, a pharmaceutical product, a nutraceutical, a food additive, a food supplement, a dairy product and a living biotherapy product (LBPs).

9. Bacterial strain for its use according to claim 8, characterized in that the composition further comprises one or more other probiotic bacterial strains, in particular chosen from the species Bifidobacterium longum, Bifidobacterium lactis, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium adolescentis, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus salivarius, Lactobacillus johnsonii, Lactobacillus salivarius, Lactococcus lactis, Enterococcus faecium, Enterococcus faecalis, Saccharomyces cerevisiae, Saccharomyces boulardii, Faecalibacterium prausnitzii, Akkermansia muciniphila, Blautia faecis, Faecalibacteium prausnitzii, Streptococcus Thermophilus or mixtures thereof, preferably chosen from the group consisting of Bifidobacterium longum NCC3001 (ATCC BAA-999), Bifidobacterium longum NCC2705 (CNCM 1-2618), Bifidobacterium longum NCC490 (CNCM 1-2170), Bifidobacterium lactis NCC2818 (CNCM 1-3446), Bifidobacterium breve strain A, Lactobacillus johnsonii NCC533 (CNCM 1-1225), Enterococcus faecium SF 68 (NCC2768; NCIMB10415), Lactobacillus casei (CNCM 1-5662 and CNCM 1-5663), Streptococcus thermophilus (CNCM 1-5334) and combinations thereof.

10. Bacterial strain for use according to claim 8, characterized in that the composition is free from any other bacteria of the Lactobacillus species.

11. Bacterial strain for use according to any one of claims 8 to 10, characterized in that the composition further comprises one or more prebiotics.

12. Non-therapeutic use of a bacterial strain of the species Limosilactobacillus mucosae, or a lysate or culture supernatant thereof, in particular as defined in any one of claims 6 to 11, for maintaining or increasing muscle mass and / or function in a subject in need thereof, in particular in a subject selected from a malnourished subject, an elderly subject, in particular a malnourished elderly subject, and a subject engaged in intense physical exercise.

13. Bacterial strain Limosilactobacillus mucosae deposited with the CNCM under accession number CNCM 1-5661.

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