Limosilactobacillus mucosae and disorders requiring increased GLP-1

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 a disorder requiring increased production of GLP-1 in a subject in need thereof, wherein the disorder is selected from (i) a disorder associated with impaired insulin sensitivity and / or blood glucose regulation, and (ii) a loss of muscle mass and / or loss of muscle function.

Description

[Technical Field]

[0001] The present invention relates to novel probiotic and prebiotic agents that stimulate the synthesis of GLP-1 by intestinal cells.

[0002] In particular, 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 a disorder requiring increased GLP-1 levels in a subject in need thereof, wherein the disorder is selected from (i) disorders associated with impaired insulin sensitivity and / or blood glucose regulation and / or (ii) loss of muscle mass and / or muscle function. The present invention also relates to non-therapeutic uses of the bacterial strain of the species Limosilactobacillus mucosae for maintaining or increasing muscle mass and / or muscle function in subjects in need thereof, particularly malnourished subjects, elderly subjects, particularly malnourished elderly subjects, and subjects engaged in strenuous physical exercise. Finally, the present invention relates to the bacterial strain Limosilactobacillus mucosae deposited at the CNCM under accession number CNCM I-5661. [Background technology]

[0003] The proportion of elderly people (aged 65 and over) is expected to account for one-third of the French population by 2050. This population is highly heterogeneous, characterized at one extreme by people who are healthy, active, well-nourished, have low sarcopenia (age-related loss of muscle mass and function), and generally live at home. Conversely, there are (at the same age) undernourished and highly sarcopenic elderly populations, who are generally dependent, live in institutions, and suffer from chronic undernutrition (Buckinx et al., Burden of frailty in the elderly population: perspectives for a public health challenge. Archives of public health = Archives belges de sante publique 2015;73(1):19). At the same time, overweight or obese people account for more than half of the population in some Western countries. In addition to an increased risk of developing diabetes or cardiovascular disease, some of these populations may also experience increased muscle wasting, which may reduce their autonomy and, above all, limit the therapeutic options available when treating obesity with a hypocaloric diet (Barazzoni et al., Sarcopenic Obesity: Time to Meet the Challenge. Obesity Facts. 2018:11(4):294-305). In addition, loss of muscle mass and muscle function may also affect individuals at any time throughout their lifespan, depending on their background and experiences. This is particularly the case for "severely burned" subjects, immobilized patients, cancer patients, or subjects who have undergone intestinal resection or who exhibit intestinal malabsorption.

[0004] Recent data suggest a causal relationship between the activity of the gut microbiota and various diseases associated with dysregulation 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 suggest interest in developing probiotic strategies. In addition, comparative physiological studies are focusing on physiopathological situations that exhibit metabolic adaptations favoring the maintenance of insulin sensitivity and muscle mass and / or a more efficient metabolic utilization of nutrients.

[0005] Overexpression of certain lactobacilli has been observed in people 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 gastrointestinal tract and microbiota of these patients are metabolically adapted to maintain energy nitrogen assimilation despite a reduced intestinal food absorption capacity (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).

[0006] Studies in which these bacteria were transplanted into axenic rats showed increases in plasma peptide concentrations, 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 is a digestive peptide produced by enteroendocrine cells in the distal ileum and colon after ingestion of a meal and has many metabolic actions, including the regulation of insulin secretion by the pancreas (as well as the regulation of food intake and transit) (Laurindo et al., GLP-1a: Going Beyond Traditional Use. Int J Mol Sci. 2022 Jan 10;23(2)). Moreover, GLP-1 analogs are currently used to improve glucose tolerance in patients, and the role of GLP-1 in Parkinson's disease and in regulating mood disorders has been further reported. 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)).The use of GLP-1a has also been shown to be effective in treating 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):575-595), liver disease (Newsome et al., "A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis." New England Journal of Medicine 384, No. 12 (March 25, 2021):1113-1124), or degenerative diseases, such as Alzheimer's disease (Femminella et al., "Evaluating the Effects of the Novel GLP-1 Analogue Liraglutide in Alzheimer's Disease" "Exenatide Once Weekly versus Placebo in Parkinson's Disease: A Randomized, Double-Blind, Placebo-Controlled Trial." Lancet (London, England) 390, No. 10103 (October 7, 2017): 1664-1675).

[0007] In particular, certain GLP-1 agonists have been shown to be associated with increased risk of muscle mass loss in obese or diabetic patients (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):903-918) or elderly patients (Abdulla et al., “Glucagon-Like Peptide 1 Infusions Overcome Anabolic Resistance to Feeding in Older Humans” It has been shown that steroid hormones may have beneficial effects on body composition, particularly the maintenance of muscle mass, in people with steroid hormones, including but not limited to those with steroid hormones (e.g., steroid hormones ...

[0008] If the bacteria resident in the distal part of the intestine (colon, distal ileum) could stimulate endogenous GLP-1 synthesis, all of the metabolic effects associated with GLP-1 and described above could be expected.

[0009] The beneficial effects of certain bacteria of the Lactobacillus genus on humans are known in the art, for example, Limosilactobacillus reuteri (L. reuteri) is known to control weight and obesity or improve insulin sensitivity and glucose homeostasis through various mechanisms and metabolites (Abuqwider et al., Limosilactobacillus reuteri in Health and Disease. Microorganisms 2022, 10, 522). Furthermore, it has been demonstrated, for example, that the Lactobacillus fermentum MG4295 (L. fermentum MG4295) bacterial strain can improve hyperglycemia in mice fed a high-fat diet, and that this bacterial strain exhibits advantageous properties for use as a probiotic (Kim et al., Limosilactobacillus fermentum MG4295 Improves Hyperglycemia in High-Fat Diet-Induced Mice. Foods. 2022, 11, 231).

[0010] Moreover, it is known in the art that certain strains of the species L. mucosae may exhibit probiotic potential, for example, for lipid metabolism, particularly for controlling hyperlipidemia (Chinese Patent Application No. CN111979145A1), as well as in the treatment of memory disorders, learning disorders, psychiatric disorders and inflammatory diseases (European Patent Application No. EP3715449A2) or even in protection against certain cardiovascular diseases (Ryan et al., MC Microbiology (2019) 19:33). Summary of the Invention [Problem to be solved by the invention]

[0011] However, to the inventors' knowledge, it has never previously been suggested that bacterial strains of the species Lactobacillus mucosae (L. mucosae) may exhibit probiotic properties that allow for the prevention and / or treatment of disorders requiring an increase in the production of GLP-1 in subjects in need of such prevention and / or treatment.

[0012] There therefore remains a need to propose novel probiotic compositions that make it possible to stimulate the production of GLP-1, depending on the subject concerned, for (i) the prevention or treatment of disorders related to impaired insulin sensitivity and / or glycemic regulation, or (ii) the prevention or treatment of loss of muscle mass and / or loss of muscle function. [Means for solving the problem]

[0013] Surprisingly, it has been shown in the examples that bacterial strains of the species Limosilactobacillus mucosae or their lysates or culture supernatants induce or increase the production of GLP-1 protein, in particular the production of GLP-1 protein by intestinal cells of human subjects.

[0014] In accordance with the first object, 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 a disorder requiring increased production of GLP-1 in a subject in need of such prevention and / or treatment, wherein the disorder is selected from (i) disorders associated with impaired insulin sensitivity and / or blood glucose regulation, and (ii) loss of muscle mass and / or loss of muscle function.

[0015] According to a particular embodiment, the subject in need is the subject that is adapted to be administered with GLP-1 receptor agonist.Particularly, the subject that is administered with GLP-1 receptor agonist is selected from the following list: insulin-resistant subject, for example, diabetic subject and overweight subject, particularly obese subject, subject that has undergone metabolic surgery, subject that is trying to control appetite, subject that suffers from liver disease, subject that suffers from cardiovascular disease, particularly subject that suffers from cardiovascular disease related to diabetes, subject that suffers from inflammation, particularly subject that suffers from inflammation related to diabetes and / or metabolic syndrome, subject that has sarcopenia, subject that has cachexia; and subject that suffers from neurodegenerative disease.

[0016] According to one embodiment, the disorder is a disorder associated with impaired insulin sensitivity and / or glycemic control selected from prediabetes, type 1 diabetes and type 2 diabetes.

[0017] According to one embodiment, the disorder is a loss of muscle mass and / or muscle function, and the subject in need is selected from elderly subjects with sarcopenia, overweight and obese subjects with diet-treated sarcopenic obesity, diabetic or pre-diabetic subjects, and / or subjects with cachexia, in particular subjects associated with cancer, subjects associated with inflammatory bowel disease or with chronic obstructive pulmonary disease, subjects associated with immobilization, subjects associated with a "severe burn" condition, subjects associated with sepsis or subjects suffering from a viral infection, subjects associated with convalescence, and / or subjects associated with immobilization, and / or subjects associated with bowel resection or intestinal malabsorption.

[0018] In particular, the bacterial strain is selected from the strain of the species L. mucosae deposited at the CNCM under accession number CNCM I-5661, the strain of the species L. mucosae deposited at DSM under accession number DSM 13345, the strain of the species L. mucosae deposited at DSM under accession number DSM 13346, the strain of the species L. mucosae deposited at DSM under accession number DSM 102820, or a combination thereof, and in particular is the strain of the species L. mucosae deposited at the CNCM under accession number CNCM I-5661.

[0019] According to one embodiment, the bacteria of the species L. mucosae are in live or dead form, preferably in live form.

[0020] In particular, the bacterial strain is comprised in a composition comprising a physiologically acceptable medium, in particular an oral composition, more particularly an oral composition selected from the group consisting of foods, beverages, pharmaceuticals, dietary supplements, food additives, food supplements, dairy products and live biotherapeutic products (LBPs).

[0021] In particular, the composition may further comprise one or more other probiotic bacterial strains, in particular Bifidobacterium longum species, Bifidobacterium lactis species, Bifidobacterium breve species, Bifidobacterium infantis species, Bifidobacterium adolescentis species, Lactobacillus acidophilus species, Lactobacillus casei species, Lactobacillus salivarius species, Lactobacillus johnsonii species, Lactobacillus johnsonii species, Lactobacillus salivarius species, Lactococcus lactis species, Enterococcus faecium species, Enterococcus faecalis species, Saccharomyces cerevisiae species, Saccharomyces boulardii species, Faecalibacterium prausnitzii species, Akkermansia muciniphila species, Blautia faecis species, Faecalibacterium prausnitzii species one or more other probiotic strains selected from the species Bifidobacterium longum NCC3001, Bifidobacterium prausnitzii, Bifidobacterium thermophilus, Bifidobacterium longum NCC3001, Bifidobacterium longum NCC3002, Bifidobacterium longum NCC3003, Bifidobacterium longum NCC3004, Bifidobacterium longum NCC3005, Bifidobacterium longum NCC3006, Bifidobacterium longum NCC3007, Bifidobacterium longum NCC3008, Bifidobacterium longum NCC3009, Bifidobacterium longum NCC3001 ...NCC3001 (ATCC BAA-999), Bifidobacterium longum NCC2705 (CNCM I-2618), Bifidobacterium longum NCC490 (CNCM I-2170), Bifidobacterium lactis NCC2818 (CNCM I-3446), Bifidobacterium breve strain A, Lactobacillus johnsonii NCC533 (CNCM I-1225), Enterococcus faecium SF 68 (Enterococcus faecium SF 68) 68) (NCC2768; NCIMB10415), Lactobacillus casei (CNCM I-5662 and CNCM I-5663), Streptococcus thermophilus (CNCM I-5334), and combinations thereof.

[0022] According to a particular embodiment, the composition does not contain any other bacteria of the Lactobacillus genus.

[0023] In particular, the composition further comprises one or more prebiotics.

[0024] According to a second aspect, the present invention relates to the non-therapeutic use of a bacterial strain of the species Limosilactobacillus mucosae or a lysate or culture supernatant thereof, in particular a bacterial strain of the species Limosilactobacillus mucosae or a lysate or culture supernatant thereof as defined according to the invention, for maintaining or increasing muscle mass and / or muscle function in a subject in need thereof, in particular a subject selected from malnourished subjects, elderly subjects, in particular malnourished elderly subjects, and subjects engaged in strenuous physical exercise.

[0025] Finally, the present invention relates to the bacterial strain Limosilactobacillus mucosae deposited at the CNCM under accession number CNCM I-5661. [Brief explanation of the drawings]

[0026] [Figure 1] Figure 1 shows the GLP-1 concentration in the supernatant after 4 hours of incubation of enteric neuroendocrine cells from SCT-1 mice with the various bacteria and conditions tested. The x-axis indicates the various conditions tested: from left to right, strain 1 (L. casei 1), strain 2 (L. casei 2), strain 3 (L. camelliae), strain 4 (L. salivarius), strain 5 (L. rhamnosus), strain 6 (L. reuleri), strain CNCM I-5661 (L. mucosae), and the control (negative, in sterile cell medium). The y-axis indicates the GLP-1 concentration (pg / mL). [Figure 2] Figure 2 shows the GLP-1 concentration in the supernatant of enteric neuroendocrine cells from SCT-1 mice as a function of incubation time in the presence of CNCM I-5661 strain (L. mucosae). The x-axis indicates incubation time, i.e., from left to right, 3 h of incubation, 4 h of incubation, and 5 h of incubation. The y-axis indicates GLP-1 concentration (pg / mL). [Figure 3] Figure 3 shows the GLP-1 concentration in the supernatant of enteric neuroendocrine cells from SCT-1 mice after 3 hours of incubation in the presence of Lactobacillus mucosae (L. mucosae) at different bacterial concentrations. The x-axis indicates the various conditions tested. From left to right: control (negative control, sterile cell medium), Lacticaseibacillus casei strain (strain A - negative control, approximately 5 x 109 CFU / mL), CNCM I-5661 strain (strain B - positive control, approximately 5 x 109 CFU / mL), CNCM I-5661 strain diluted 1 / 10 (strain B, diluted - approximately 5 x 108 CFU / mL), DSM 13345 (strain C, approximately 2 x 109 CFU / mL), DSM 13345 strain diluted 1 / 10 (strain C, diluted, approximately 2 x 108 CFU / mL), DSM 13346 strain (strain D, approximately 4 x 109 CFU / mL), and DSM 13346 diluted 1 / 10. The following strains were diluted: DSM 13346 (strain D, diluted approximately 4 x 10 CFU / mL), DSM 102820 (strain E, diluted approximately 5 x 10 CFU / mL), and DSM 102820 (strain E, diluted approximately 2 x 10 CFU / mL). The Y-axis indicates the GLP-1 concentration (pg / mL). Significant difference (P < 0.05). As above, there is a clear difference between the complete absence of detectable secretion (under the negative control conditions) and the detectable secretion of GLP-1 when all strains are combined under conditions with the L. mucosae bacteria. However, statistics were not calculated (lack of data), and this does not seem necessary in light of the results. [Figure 4]Figure 4 shows the hindlimb muscle weights (mg / g of rat body weight) for various groups of aged rats (20 months) after 1 month of testing. The rat groups tested are as follows: (from left to right on the x-axis) rats with ad libitum (AL), rats restricted to 75–80% of their ad libitum intake (R), rats restricted and supplemented with CNCM-I5661 strain of L. mucosae (R+L mucosae I5561), and rats restricted and supplemented with L. casei (R+L casei). DETAILED DESCRIPTION OF THE INVENTION

[0027] The present inventors have carried out extensive research to identify the potential of a bacterial species, namely the species Limosilactobacillus mucosae, for use in the prevention and / or treatment of disorders requiring an increase in the production of GLP-1 in a subject in need of such prevention and / or treatment.

[0028] In fact, the present inventors unexpectedly showed that Limosilactobacillus mucosae can stimulate the synthesis of GLP-1 by enterocytes in vitro, whereas other strains of different lactobacilli species are unable to induce this synthesis of GLP-1 by enterocytes. Furthermore, Limosilactobacillus mucosae exhibited excellent resistance to the environmental conditions encountered in the intestine (acidic pH of the stomach and bile salts) and excellent adhesion ability to enterocytes. Limosilactobacillus mucosae is abundant in patients with short bowel syndrome (Joly et al., Biochemistry 2010; PMID:20172013) and can colonize the virgin digestive tract (germ-free animals) after fecal transfer (Gillard et al., Front Physiol. 2017). This ability of Limosilactobacillus mucosae to increase the synthesis of the intestinal peptide GLP-1 and persist in the gut 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 host energy and nitrogen metabolism. Finally, we have shown that administration of Limosilactobacillus mucosae can increase muscle mass in a sarcopenic rodent model.

[0029] Limosilactobacillus mucosae

[0030] The present invention relates to the use of a bacterial strain of the species Limosilactobacillus mucosae or a lysate or culture supernatant thereof.

[0031] For the purposes of the present invention, the term "lysate" is used interchangeably to designate the entire lysate obtained by lysis of a microorganism, or only a fraction thereof.

[0032] Dead bacterial cells can be obtained by any method known to those skilled in the art.

[0033] Bacterial cell lysates consist of all or part of the intracellular biological components, as well as cell wall and membrane components. It includes a cytoplasmic fraction containing, among other things, enzymes such as lactate dehydrogenase, phosphatase, phosphoketolase, and transaldolase. By way of example, cell wall components are, among other things, peptidoglycan, murein or mucopeptides, and teichoic acids, and cell membrane components are composed of glycerophospholipids.

[0034] The bacterial cell lysate can be obtained by various techniques, for example by exposing the bacterial cells to osmotic shock, heat shock, ultrasound, etc. More particularly, the lysate can be obtained according to the technique described in U.S. Pat. No. 4,464,362.

[0035] Within the meaning of the present invention, "culture supernatant" refers to the culture medium in which the bacterial strain was present during its cultivation, and may also be referred to herein by the term "extracellular medium." In particular, the culture supernatant may contain metabolites (also called extracellular metabolites) produced and secreted by the bacteria. Examples of metabolites are, for example, peptides, glycopeptides, or lipopeptides produced by the bacteria. The culture supernatant may be crude or may have undergone one or more processes, such as filtering, concentrating, freeze-drying, or heating. These techniques for transforming bacterial culture supernatants are known to those skilled in the art.

[0036] The composition of the culture supernatant varies depending on the culture conditions of the bacterial strain and the cell culture method. When the biomass is growing or in an active state, the culture supernatant mainly contains extracellular metabolites, but at the end of the stationary phase and in cultures where microbial lysis is significant, it also contains intracellular metabolites. During lysis, some cells die and others lose the integrity of their membranes, so that the supernatant contains not only cell walls from dead cells but also intracellular metabolites.

[0037] Moreover, the culture supernatant may also contain bacterial cells of the species Limosilactobacillus mucosae in a live or dead state.

[0038] Limosilactobacillus mucosae is a rod-shaped bacterial species of lactic acid bacteria first isolated from the intestine of pigs. It exhibits mucus adhesion activity.

[0039] Limosilactobacillus mucosae is a Gram-positive bacterium that is an obligate anaerobe, but can grow to a reduced extent in the presence of oxygen. This bacterial species has been described in particular by Roos et al. (2000, International Journal of Systematic and Evolutionary Microbiology, Vol. 251-258). This bacterial species has been described in the microbiota of humans 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, Duee PH, Cherbuy C, Thomas M. Biochemistry. 2010 Jul;92(7):753-61).

[0040] Regarding the designation of certain probiotics, particularly bacteria of the Lactobacillus genus, it is important to note recent changes in their taxonomic classification, as reported in the paper by Zheng et al. (2020, Int. J Syst Evol Microbiol, Vol. 70:2782-2858). Therefore, in line with these taxonomic changes, certain probiotics of the Lactobacillus genus described in previously published literature are designated herein according to the new nomenclature now in effect.

[0041] Thus, the bacterial species known today as Limosilactobacillus mucosae can also be identified in the literature as Lactobacillus mucosae.

[0042] A suitable bacterial strain of Lactobacillus mucosae according to the invention can be obtained from the feces of a subject suffering from short bowel syndrome.

[0043] According to a particular embodiment, the bacterial strain according to the invention is selected from the strain of the species L. mucosae deposited at the CNCM under accession number CNCM I-5661, the strain of the species L. mucosae deposited at DSM under accession number DSM 13345, the strain of the species L. mucosae deposited at DSM under accession number DSM 13346, the strain of the species L. mucosae deposited at DSM under accession number DSM 102820, or a combination thereof, and in particular is the strain of the species L. mucosae deposited at the CNCM under accession number CNCM I-5661.

[0044] According to a particular embodiment, the bacteria of the species L. mucosae are in live or dead form, preferably in live form.

[0045] In the sense of the present invention, "dead bacterial strains" refer to bacterial cells that are no longer able to grow and therefore are unable to form colonies in culture. Unlike lysates, dead bacterial strains retain all of their membrane integrity.

[0046] Killed bacterial strains can be obtained by any known cell death method, and according to a particular embodiment of the present invention, killed bacterial strains according to the present invention can in particular be obtained by exposure to high heat (e.g. by exposure to a UHT protocol).

[0047] Thus, for the purposes of the present invention, and particularly in the Examples herein, the term "live" refers to living bacterial cells, including stabilized bacterial cells, i.e., viable and resurrectable bacterial cells (by any known method of stabilization, for example, by freezing, lyophilization, or spray drying), unless otherwise specified.

[0048] composition

[0049] The present specification also relates to a composition comprising a bacterial strain of the species Limosilactobacillus mucosae or a lysate or culture supernatant thereof.

[0050] Thus, according to a particular embodiment, the bacterial strain according to the invention is contained in a composition comprising a physiologically acceptable medium.

[0051] The term "physiologically acceptable medium" is intended to mean a medium compatible with the organism of the individual to whom the composition must be administered. This can be, for example, a non-toxic solvent, such as water. The medium can also be a food, especially when the bacterial strain according to the invention is contained in a nutritional composition as defined below. The medium can also be mucus, for example snail mucus. Mucus suitable as a medium according to the invention can 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).

[0052] In particular, the vehicle is compatible with oral administration.

[0053] The composition described can be a nutritional composition.

[0054] For example, an athletic subject who needs to maintain or increase muscle mass does not exhibit any pathological symptoms and only requires nutritional supplementation. According to another example, the composition according to the present specification can be a nutritional composition intended for elderly or overweight people who are undernourished, for example, people who are undernourished because they are on a diet.

[0055] The present invention also relates to a pharmaceutical composition comprising a bacterial strain of Lactobacillus mucosae (L. mucosae) or a lysate or culture supernatant thereof, intended for a subject presenting with or likely to present with a pathology for which the composition has a preventive or therapeutic effect. By way of example, the composition according to the present invention comprises a pharmaceutical composition intended to prevent or treat insulin sensitivity and / or glycemic dysregulation, such as in diabetes or prediabetes.

[0056] However, unless otherwise indicated, compositions containing bacterial strains of the species L. mucosae do not differ in their general characteristics as defined herein depending on whether they are nutritional or therapeutic compositions. Thus, pharmaceutical compositions are essentially distinguished from nutritional compositions by the fact that they have a preventive and / or therapeutic effect on a disease in the subject to which they are administered. Each of these compositions also fulfills its own regulatory function and is distinguished by its mode of action. In fact, pharmaceutical compositions exert a "pharmacological, immunological, or metabolic effect," while nutritional compositions exert a "nutritional or physiological" effect.

[0057] In some embodiments of the compositions according to the present invention, a bacterial strain of the species L. mucosae is used as the only bacterial strain present in the composition.

[0058] In certain other embodiments of the compositions according to the present specification, the bacterial strain of the L. mucosae species is combined with bacteria of one or more other probiotic bacterial strains, including commensal probiotic bacterial strains.

[0059] 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.

[0060] Probiotics can be selected 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), Lacticaseibacillus paracasei, 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 plantarum) (currently Lactiplantibacillus plantarum subsp. plantarum)plantarum), Lactococcus lactis, Enterococcus faecium, Enterococcus faecalis, Saccharomyces cerevisiae, Saccharomyces boulardii, Akkermansia muciniphila, Blautia faecis, Faecalibacterium prausnitzii, Streptococcus thermophilus, or a combination thereof.

[0061] According to a particular embodiment, the described compositions may be combined with one or more other probiotic bacterial strains, in particular Bifidobacterium longum species, Bifidobacterium lactis species, Bifidobacterium breve species, Bifidobacterium infantis species, Bifidobacterium adolescentis species, Lactobacillus acidophilus species, Lactobacillus casei species, Lactobacillus salivarius species, Lactobacillus johnsonii species, Lactobacillus johnsonii species, Lactobacillus salivarius species, Lactococcus lactis species, Enterococcus faecium species, Enterococcus faecalis species, Saccharomyces cerevisiae species, Saccharomyces boulardii species, Faecalibacterium prausnitzii species, Akkermansia muciniphila species, Blautia faecis species, Streptococcus thermophilus one or more other probiotic strains selected from the Bifidobacterium longum NCC3001 (ATCC BAA-999), Bifidobacterium longum NCC2705 ...NCC2705 (CNCM 1-2618, as cited in Canadian Patent Application Publication No. CA2761573A1), Bifidobacterium longum NCC490 (CNCM I-2170, as cited in International Publication No. WO2006037922A1), Bifidobacterium lactis NCC2818 (CNCM I-3446, as cited in International Publication No. WO2008116916A1), Bifidobacterium breve strain A, Lactobacillus johnsonii NCC533 NCC533 (CNCM I-1225 cited in WO2017060468), Enterococcus faecium SF 68 (NCC2768; NCIMB10415), Lactobacillus casei (CNCM I-5662 and CNCM I-5663 cited in Giron et al., Front Nutr. 2022;9:928798, published online 2022 Aug 10), Streptococcus thermophilus (CNCM I-5334 cited in EP3826655B1), and combinations thereof.

[0062] In certain embodiments, the composition does not include any other bacteria of the Lactobacillus species.

[0063] In some embodiments, the composition also includes one or more prebiotics. The term "prebiotic" is used in its conventional sense in the art. Prebiotics consist of food substances that promote the growth of probiotic bacteria, including bacteria found in the intestinal microbiota.

[0064] Non-limiting examples of prebiotics include oligosaccharides, which may optionally contain fructose, galactose, or mannose; dietary fiber, particularly fermentable fiber, soy fiber; inulin; human milk oligosaccharides (HMO), polyphenols, chicory, mucus, and combinations thereof. Preferred prebiotics are fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), isomalto-oligosaccharides (IMO), xylo-oligosaccharides (XOS), arabinoxylo-oligosaccharides (AXOS), mannan-oligosaccharides (MOS), soybean oligosaccharides, glycosyl sucrose (GS), lactosucrose (LS), lactulose (LA), palatinose-oligosaccharides (PAO), maltooligosaccharides, resistant starch, gums and / or hydrolysates thereof, pectin and / or hydrolysates thereof, or combinations thereof.

[0065] Prebiotics can also include peptides, proteins, and complex secretions of peptides, sugars, or sulfur, such as mucus (e.g., intestinal mucus). The beneficial effects of mannan oligosaccharides and L. mucosae have been tested in pigs (PMID: 34879142; J Anim Sci. 2021 Dec 1; 99(12)). It has also been shown that a high-fiber diet can induce the cultivation of L. mucosae (Lactobacillus Mucosae Strain Promoted by a High-Fiber Diet. Microorganisms. 2020 Aug 12; 8(8):1225. PMID: 32806628).

[0066] In some embodiments, the composition comprises a combination of a probiotic and a prebiotic, which is referred to as a "symbiotic." The term "symbiotic" is used in its conventional sense in the art. The purpose of a synbiotic is to improve the survival rate and enhance the biological properties of the probiotic.

[0067] Non-limiting examples of symbiotics include combinations of bifidobacteria / fructooligosaccharides, lactobacillus / lactilol, or even bifidobacteria / galactooligosaccharides.

[0068] In some embodiments, the composition additionally comprises one or more vitamins. The vitamins can be folic acid, vitamin B12, and vitamin B6, particularly folic acid, vitamin B12, and particularly folic acid. In some embodiments, the composition includes one or more fat-soluble vitamins, such as one or more of vitamin A, vitamin D, vitamin E, and vitamin K, or a water-soluble vitamin, such as vitamin C.

[0069] In some embodiments, the composition includes one or more polyphenols, such as flavanols, flavanones, flavonols, hydroxycinnamic acids, and anthocyanins.

[0070] In some embodiments, the composition further comprises one or more minerals. The minerals can be selected from sodium, potassium, chloride, calcium, phosphate, magnesium, iron, zinc, copper, selenium, manganese, fluorine, iodine, chromium, or molybdenum. The minerals are usually added in the form of salts. The minerals can be added alone or in combination.

[0071] In some embodiments, the compositions herein generally include a support or additive. A "support" or "additive" refers to a substance suitable for administration and includes any substance known in the art, such as a liquid, gel, solvent, liquid diluent, solubilizer, etc., which is non-toxic and does not adversely interact with the components of the composition. Examples of nutritionally acceptable carriers include, for example, water, saline, alcohol, silicone, wax, petrolatum, vegetable oil, polyethylene glycol, propylene glycol, liposomes, sugar, gelatin, lactose, amylose, magnesium stearate, talc, surfactants, silicic acid, viscous paraffin, perfume oils, monoglycerides and diglycerides of fatty acids, petroleum fatty acid esters, hydroxymethylcellulose, polyvinylpyrrolidone, etc.

[0072] In some embodiments, the composition further comprises any other ingredients or additives known to be used in the type of composition under discussion, including, but not limited to, proteins, amino acids, carbohydrates, oligosaccharides, lipids, nucleotides, nucleosides, other vitamins, minerals, bacterial metabolites, bioactive molecules, and other micronutrients.

[0073] For example, the bacterial strain according to the present invention can be combined with a protein to limit muscle wasting in the subject to which it is administered.

[0074] According to another example, the bacterial strains according to the present invention can be combined with n-3 polyunsaturated fatty acids to increase insulin sensitivity in a subject.

[0075] In some embodiments, the composition contains a carbohydrate source, for example in the form of a prebiotic, or if present in the composition, in the form of a prebiotic. Although any carbohydrate source typically found in infant formulas can be used, such as lactose, sucrose, maltodextrin, starch, and mixtures thereof, the preferred carbohydrate source is lactose.

[0076] In some embodiments, the compositions herein comprise a nutritional composition.

[0077] In some embodiments, the nutritional composition is selected from a complete food composition, a food supplement, a dietary supplement composition, etc. The compositions herein can be used as food ingredients and / or animal feed ingredients. The food ingredients can be in the form of a solution or a solid, depending on the intended use and / or the method of application and / or administration. As used herein, the term "food" refers to a liquid (i.e., beverage), solid, or semi-solid dietary composition, particularly a complete food (food replacement) composition that does not require additional nutrients or a food supplement composition. A food supplement composition does not completely replace the provision of nutrients by other means. As used herein, the term "food ingredient" includes functional foods or formulations that are or can be added to foods as food supplements. "Nutritional food" or "dietary supplement" or "functional" refers to a food containing ingredients that can have a beneficial effect on health or improve physiological function. "Food supplement" refers to a food intended to supplement the normal diet. Food supplements are concentrated sources of nutrients or other substances that have a nutritional or physiological effect when taken alone or in small amounts in combination. In accordance with this specification, the term "functional food" is used to refer to foods and related products that emphasize not only nutritional and taste value, but also the presence of ingredients that have beneficial physiological effects.

[0078] In some embodiments, the composition is a fermented dairy product or milk-based product, which is preferably administered or ingested orally one or more times daily. Fermented dairy products include dairy products such as, but not limited to, desserts, yogurt, yogurt drinks, cottage cheese, kefir, fermented milk drinks, buttermilk, cheese, salad dressings, low-fat spreads, cream cheese, soy milk drinks, ice cream, etc.

[0079] In some embodiments, the composition is a fermented product based on plant matrices.

[0080] Alternatively, in some embodiments, the nutritional composition and / or nutritional supplement composition can be a non-dairy or non-fermented dairy product. Non-fermented dairy products can include ice cream, nutritional bars, condiments, etc. Non-dairy products can include powdered drinks, nutritional bars, etc. The product can be produced using known methods, such as adding an effective amount of a bacterial strain of the Limosilactobacillus mucosae (L. mucosae) species, or an effective amount of a bacterial combination including a bacterial strain of the Limosilactobacillus mucosae (L. mucosae) species, to a food base, such as skim milk or a milk or milk-based composition, and then fermenting using any known technique. In some embodiments, the composition is a beverage, which can be a functional or therapeutic beverage, a thirst-quenching beverage, or a conventional beverage. By way of example, compositions according to the present invention may be used as ingredients for carbonated drinks, fruit juices, or beverages containing whey protein, tea, cocoa drinks, dairy drinks, yogurt including drinking yogurt, cheese, ice cream, popsicles and desserts, confectionery, biscuits, cakes and cake mixes, snacks, health foods and beverages, icings, acidified soy milk / juice, aseptic / reduced chocolate drinks, bar mixes, powdered drink mixes, calcium fortified soy milk and chocolate, calcium fortified coffee drinks.

[0081] In some embodiments, the composition includes any other ingredients or additives known to be used in the type of composition under discussion. Non-limiting examples of such ingredients include proteins, amino acids, carbohydrates, oligosaccharides, lipids, prebiotics or probiotics, nucleotides, nucleosides, other vitamins, minerals, and other micronutrients.

[0082] In certain other embodiments, a bacterial strain of the L. mucosae species, optionally in combination with one or more other strains of probiotic bacteria, is administered to a subject in the form of a pharmaceutical composition, which can correspond to a Live Biotherapeutic Product (LBP) product composed of live enterobacteria (Front Med (Lausanne) Rouanet et al., 2020 Jun 19;7:237. doi:10.3389 / fmed.2020.00237). For example, the bacteria of interest can be combined with pharmaceutically acceptable additives and, optionally, a sustained-release matrix, such as a biodegradable polymer, to form a therapeutic composition. The terms "pharmaceutical" or "pharmaceutically acceptable" refer to molecular entities and compositions that do not elicit adverse, allergic, or other reactions when administered to mammals, particularly humans, as applicable. Pharmaceutically acceptable carriers or additives refer to non-toxic solid, semi-solid, or liquid fillers, diluents, encapsulating materials, or any type of formulation auxiliary. In the pharmaceutical compositions herein for oral, sublingual, subcutaneous, intramuscular, intravenous, transdermal, topical, or rectal administration, one active ingredient or a combination of active ingredients can be administered to animals and humans in unit dosage form mixed with a conventional pharmaceutical carrier. 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 nasal dosage forms, and rectal dosage forms. Typically, pharmaceutical compositions contain a pharmaceutically acceptable vehicle for injection formulations. These are in particular isotonic sterile saline solutions (such as mono- or di-sodium phosphate, sodium chloride, potassium chloride, calcium chloride or magnesium chloride, or combinations of these salts) or dry compositions, in particular lyophilized ones, which can be constituted as injectable solutions, optionally by adding sterile water or physiological serum.The pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions; formulations containing 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 formulation must be sterile and must be fluid to the extent that it can be easily squeezed.

[0083] The pharmaceutical compositions must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms, such as bacteria and fungi. Solutions containing the compounds of the present disclosure in free base or pharmaceutically acceptable salt form can be prepared in water, suitably mixed with a surfactant, such as hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof, as well as in oils. Under ordinary conditions of storage and use, these formulations contain a preservative to prevent the growth of microorganisms. At least one bacterial strain of the Limocilactobacillus mucosae (L. mucosae) species according to the present invention can be incorporated into the composition in neutral or salt form. Pharmaceutically acceptable salts include acid addition salts (formed with the free amino groups of proteins) formed, for example, with inorganic acids, such as hydrochloric or phosphoric acids, or organic acids, such as acetic acid, oxalic acid, tartaric acid, mandelic acid, and similar acids. Salts formed with the free carboxyl groups can also be derived from inorganic bases such as, for example, sodium, potassium, ammonium, calcium, or ferric hydroxides, and from organic bases such as, for example, isopropylamine, trimethylamine, histidine, procaine, and the like.

[0084] According to a particular embodiment, the bacterial strain according to the invention is comprised in an oral composition, more particularly in an oral composition selected from the group consisting of a food, a beverage, a pharmaceutical product, a dietary supplement, a food additive, a food supplement, a dairy product, and a live biotherapeutic product (LBP).

[0085] As used herein, the term "therapeutically effective amount" refers to an amount of a treatment (e.g., a prophylactic or therapeutic agent) sufficient to reduce the severity and / or duration of a disease, alleviate one or more of its symptoms, prevent the progression of a disease, or cause the regression of a disease; or to prevent 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 one or more therapeutic effects of another therapy (e.g., another therapeutic agent) useful for treating a disease. Typically, in pharmaceutical compositions according to the present invention, the bacterial strain of the L. mucosae species is present in an amount sufficient to induce a decrease in insulin resistance in a treated subject. Measuring insulin resistance in a subject can be performed using any technique known to those skilled in the art. Preferably, measuring insulin resistance in a subject is performed by calculating the HOMA IR index, as shown in the Examples. The HOMA IR method (short for "Home Ostasis Model Assessment for Insulin Resistance") was developed from mathematical modeling of the quantitative responses of major organs of glucose metabolism. The HOMA IR index value is obtained using plasma insulin or C-peptide levels and fasting blood glucose levels (Sheen, 2007, Therapy, Vol. 62:311-318). The occurrence and / or level of insulin resistance can also be established by measuring fasting blood sugar, fasting insulin, or an OGTT test (Oral Glucose Tolerance Test or provoked hyperglycemia test—see, for example, "Measurement of insulin resistance and glucose tolerance," 2006, Haute Autorite de Santé (HAS), France).

[0086] In the composition according to the present invention, whether it is a nutritional or food composition, if appropriate a food supplement or a pharmaceutical composition, the germs or bacteria can be present in various forms, for example in liquid or powder form. The germs or bacteria can be in freeze-dried form.

[0087] The amount of L. mucosae bacteria administered to a subject can vary depending on the physiological condition of the subject, particularly depending on the level of nutrient intake imbalance relative to the subject's nutritional requirements. The amount of L. mucosae bacteria to be administered to a subject can be easily adjusted by those skilled in the art.

[0088] In a preferred embodiment, whether the composition is a nutritional or pharmaceutical composition, the composition comprises at least 10g of cereals suitable for daily intake, preferably daily oral intake. 3 The sample contains a bacterial load of the species Lactobacillus mucosae in an amount of colony forming units (i.e., "CFU") of 1000 mg / ml.

[0089] In these preferred embodiments, the daily intake, in particular the daily oral intake, of the bacteria of the species Lactobacillus mucosae (L. mucosae) is 10 13 100 colony forming units (i.e., "CFU") or less.

[0090] In embodiments in which the composition additionally contains other probiotic bacteria, the amount of these probiotic bacteria is determined by a person skilled in the art based on their general knowledge. The amount of these other probiotic bacteria is 10 times the amount of other probiotic bacteria. 3 ~10 13 It can change into an individual.

[0091] In some embodiments, the compositions herein generally include a carrier or vehicle. A "carrier" or "vehicle" refers to a substance suitable for administration and includes any substance known in the art, such as any liquid, gel, solvent, liquid diluent, solubilizer, etc., that is non-toxic and does not adversely interact with the components of the composition. Examples of nutritionally acceptable carriers include, for example, water, saline, alcohol, silicone, wax, petrolatum, vegetable oils, polyethylene glycol, propylene glycol, liposomes, sugar, gelatin, lactose, amylose, magnesium stearate, talc, surfactants, silicic acid, viscous paraffin, flavor oils, mono- and diglycerides of fatty acids, petroleum fatty acid esters, hydroxymethylcellulose, polyvinylpyrrolidone, etc.

[0092] In other embodiments of the compositions according to the present invention, the composition is in the form of a pharmaceutical composition that includes one or more pharmaceutically acceptable excipients.

[0093] Such pharmaceutical compositions may be presented in the form of a package containing multiple dosage units.

[0094] The term "dosage unit" is used in its conventional sense in medicine (eg, tablet, capsule, pill, contents of an ampoule, etc.).

[0095] use

[0096] GLP-1 is a peptide that has many metabolic effects in the host, in particular it improves insulin secretion by the pancreas, promotes glucose tolerance, and therefore optimizes the host's energy and nitrogen metabolism. The inventors have surprisingly shown that bacteria of the Limosilactobacillus mucosae type are able to increase the production of GLP-1 in vitro and thus prevent or limit the metabolic effects of the following diseases or conditions associated with a deficiency in the action of GLP-1: insulin resistance (e.g. type 2 diabetes), metabolic disorders, difficulty regulating food intake, regulation of gastrointestinal obstruction, etc.

[0097] As is clear from the present specification, the bacterial strain of the species Lactobacillus mucosae (L. mucosae) according to the present invention or a composition comprising the same mainly comprises: (i) a disorder associated with impaired insulin sensitivity and / or blood glucose regulation, or (ii) loss of muscle mass and / or muscle function It is intended to prevent and / or treat

[0098] According to a particular embodiment, the loss of muscle mass and / or muscle function is associated with insulin resistance.

[0099] These disorders are associated with a deficiency in the action of GLP-1.

[0100] The bacterial strain of the species L. mucosae according to the invention or a composition comprising it may be particularly useful in the prevention and / or treatment of transit-related disorders or disorders of appetite regulation.

[0101] According to a particular embodiment, the bacterial strain is contained in a composition comprising a physiologically acceptable medium, as defined above.

[0102] In the context of this specification, the term "prevent" or "prevention" refers to reducing to a lower degree the risk or probability of occurrence of a given phenomenon, i.e., in this invention, a disorder that requires an increase in GLP-1 levels.

[0103] As used herein, the term "treat" or "treatment" refers to the alleviation or attenuation of a pathological process, or the alleviation or attenuation of one or more symptoms associated with a pathological process, particularly one of the disorders described herein, which requires an increase in the level of GLP-1.

[0104] The present specification relates to nutritional and therapeutic uses of the bacterial strains or compositions defined in this application.

[0105] The compositional characteristics of the nutritional and therapeutic compositions, including various embodiments, are described in detail herein, including the amount of one or more active ingredients, particularly the amount of bacteria of the species Lactobacillus mucosae (L. mucosae), contained in these compositions.

[0106] (i) Disorders associated with impaired insulin sensitivity and / or blood glucose regulation

[0107] Dysregulation of insulin sensitivity, such as the development of insulin resistance, specifically refers to a situation in which liver, muscle, and fat cells become resistant to insulin. This results in less glucose being taken up by these cells, and the glucose remains in the blood. In response to insulin resistance, insulin-secreting cells in the pancreas tend to produce more insulin (hyperinsulinemia) and may eventually become depleted. This leads to insufficient insulin production and excessively high blood sugar levels (hyperglycemia). Insulin resistance may also be involved in other types of metabolism controlled by insulin, such as protein metabolism. In fact, insulin, combined with a meal, is the primary stimulator of muscle protein anabolism. Therefore, insulin resistance contributes to muscle wasting due to a lack of anabolism in muscle, especially during a meal.

[0108] Blood glucose regulation is the process of maintaining blood glucose levels (known as blood glucose levels) at beneficial levels. This regulation is part of the body's internal homeostasis. 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 referred to as dysregulation.

[0109] According to the present specification, the main disorders associated with insulin sensitivity and / or glycemic dysregulation are prediabetes, type 1 diabetes, and type 2 diabetes, which may or may not be caused by obesity.

[0110] However, activation by GLP-1 of receptors expressed at the level of insulin cells (β) and certain peripheral tissues not only stimulates insulin secretion (insulinotropic effect), but also activates insulin gene transcription, increases insulin biosynthesis, and inhibits glucagon release (static glucagon effect).

[0111] "Prediabetes" refers to a physiopathological condition characterized by elevated blood glucose levels, particularly those below the threshold that defines type 2 diabetes. Fasting blood glucose levels are considered (i) normal when they are between 0.70 and 1.10 g / L, (ii) indicative of prediabetes when they are between 1.10 and 1.25 g / L, and (iii) indicative of diabetes when they are greater than 1.25 g / L. Prediabetes generally causes no symptoms and is often accompanied by obesity, dyslipidemia, and hypertension. It is a risk factor for cardiovascular disease. Prediabetes is particularly characterized by impaired glucose tolerance. Stimulation of pancreatic insulin and glucagon secretion by GLP1 regulates glycemic fluctuations by lowering fasting blood glucose. GLP1 induces glucose uptake and storage in the liver and inhibits gluconeogenesis. Furthermore, GLP1 not only increases insulin secretion but also plays a role in improving insulin sensitivity in many tissues, including muscle (Muller et al., 2019, Mol Metab).

[0112] "Type 1 diabetes" or "T1D" refers to a chronic disease characterized by a complete lack of insulin production in an individual. Therefore, individuals living with type 1 diabetes rely on daily insulin injections or an insulin pump to maintain survival. As previously described for prediabetes, GLP1 plays many roles in glycemic control, including stimulating insulin and glucagon secretion, glucose uptake and storage in the liver, suppressing gluconeogenesis, and improving insulin sensitivity in many tissues.

[0113] "Type 2 diabetes" or "T2D" refers to a chronic disease that occurs when the pancreas does not produce enough insulin (a hormone that regulates blood sugar levels) or when the body cannot effectively use the insulin that is produced.

[0114] According to a particular embodiment, the disorder associated with dysregulation of blood glucose is type 2 diabetes.

[0115] (ii) loss of muscle mass and / or muscle function

[0116] According to a particular embodiment, the disorder to be prevented and / or treated is a loss of muscle mass and / or muscle function, characterized by a subject in need thereof, selected from elderly subjects with sarcopenia, overweight and obese subjects with diet-treated sarcopenic obesity, subjects with cachexia, in particular inflammatory bowel disease or chronic obstructive pulmonary disease, immobilized subjects, subjects who have undergone bowel resection or intestinal malabsorption.

[0117] Subjects who have lost muscle mass due to the conditions described above are generally resistant to the anabolic effects of diet and / or the effects of insulin. Although subjects experiencing significant muscle wasting often exhibit insulin resistance, not all insulin-resistant or prediabetic subjects necessarily experience muscle wasting, a phenomenon that can progress gradually over time, and the development of muscle wasting and insulin resistance are strongly metabolically linked (Daily and Park, 2022 Cells-DOI:10.3390 / cells11030338).

[0118] In fact, GLP-1 is known to have advantageous properties that allow it to optimize nutrient energy utilization and limit muscle wasting (Hong et al., Journal of Cachexia, Sarcopenia and Muscle 2019;10:903-918), especially 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).

[0119] Muscle mass loss can be measured by various techniques known to those skilled in the art, such as mid-upper arm circumference, bioelectrical impedance, bioenergetic X-ray absorptiometry (DXA), and CT scan (Mareschal et al., 2019, Journal of Clinical Medicine, doi:10.3390 / jcm8071040).

[0120] Loss of muscle function (strength, power, physical ability) can be measured by various techniques known to those skilled in the art, such as the grip strength test (grip strength test using a dynamometer), 6-minute walking speed, 30-second chair stand test, the Short Physical Performance Battery (SPPB) test (which is a combination of walking speed, balance, and standing), and the "timed up and go" test (consisting of rising 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).

[0121] Within the meaning of this specification, an "elderly subject" refers to a human subject or a non-human mammalian subject, such as a pet animal, such as a dog or cat, who exhibits signs of aging, such as decreased metabolic function (e.g., absorption, digestion, excretion, tissue and organ dysfunction), impaired mobility, and decreased resistance to external aggression. In the case of humans, an "elderly subject" or "elderly person" refers to a subject aged 65 or older. In the case of canines, particularly dogs, an "elderly subject" refers to (i) a subject aged 12 or older in the case of small canines, particularly small dogs; (ii) a subject aged 9 or older in the case of medium canines, particularly medium dogs; or (iii) a subject aged 7 or older in the case of large canines, particularly large dogs. In the case of felines, particularly cats, an "elderly subject" refers to a subject aged 13 or older.

[0122] Sarcopenia (translated from Greek as "lack of flesh") was originally defined as a loss of skeletal muscle mass, but is now characterized by muscle mass loss associated with functional decline (European Working Group on Sarcopenia in Older People (EWGSOP) - Cruz Jentoft et al., 2019, Age and Aging). Between the ages of 20 and 30, even healthy individuals lose muscle mass by approximately 1% per year. This rate accelerates between the ages of 50 and 60. Sarcopenia impacts physical performance, promotes walking disorders, and constitutes a factor for frailty and increased risk of dependency, especially in older adults. It should be noted that sarcopenia not only affects elderly individuals but also insulin-resistant populations, such as obese individuals, and such cases are referred to as sarcopenic obesity (Working Group of the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) - Donini et al., 2022, Obesity Facts). This muscle wasting can also occur more quickly, especially in highly catabolic situations, such as cancer and its associated intensive treatments, such as chemotherapy. In this case, it is referred to as cachexia (see below). Sarcopenia is associated with an increased risk of falls and fractures, leading to immobilization, which exacerbates sarcopenia. Thus, a snowballing decline in muscle mass and function with aging is observed.

[0123] "Obesity" refers to a physiopathological condition manifested in particular by weight gain and excess adipose tissue, generally induced by an obesogenic diet (including, in particular, excessive intake of high-calorie foods, genetic predisposition, or insufficient or no physical activity). An individual diagnosed as obese has a body mass index (BMI) greater than 30. According to the official definition of the World Health Organization (WHO), BMI is an indicator of the health risks associated with being overweight or underweight. BMI is calculated by dividing an individual's weight (in kilograms) by the square of the individual's height (in meters). BMI values ​​are associated with specific body types according to the classification given by the WHO.

[0124] Unlike an "obese" individual, an "overweight individual" refers to an individual without a physiopathological cause. Overweight individuals often also have excess adipose tissue. Individuals are generally considered overweight if they have a BMI (body mass index) of 25-30.

[0125] When an individual has both excess fat mass and a loss in lean muscle mass, it is called sarcopenic obesity, a clinical condition that occurs most frequently in older adults.

[0126] "Cachexia," or severe physical wasting, is characterized by the wasting of fat tissue and muscle, among other things. Cachexia is common in many diseases, including cancer, which is difficult or impossible to control or cure, and, as noted above, develops over a much shorter period of time (days to weeks). Cancer, particularly pancreatic and gastric cancer, can cause severe cachexia. Patients can lose 10-20% of their body weight. Cachexia is also associated with other catabolic diseases, such as inflammatory bowel disease or chronic obstructive pulmonary disease, viral infections, or sepsis.

[0127] Decreased mobility has been shown to be associated with a decline in muscle mass index and muscle strength. The reverse is also true, as a decline in mobility and physical activity may exacerbate or cause sarcopenia in a broad sense. Therefore, immobilized subjects are more likely to develop a loss of muscle mass and / or muscle function. In particular, in the context of this specification, this may include subjects recovering from a fall and / or being immobile.

[0128] Subjects with known "severe burn" conditions, including hypermetabolic diseases (sepsis, viral infections, and even cancer), are characterized by significantly higher demands for macronutrients and micronutrients to meet the increased needs associated with the pathology, particularly due to the healing process (in the case of "severe burn patients") and the inflammatory response (Knuth et al. 2021, American Journal of Physiology, Cell Physiology). Furthermore, due to high inflammation, resistance to dietary anabolism and the aforementioned insulin resistance are commonly observed as determinants of obesity and sarcopenia in elderly subjects.

[0129] GLP-1 helps optimize nutrient utilization in subjects with intestinal absorption disorders or those who have undergone intestinal resection. In fact, increased GLP-1 production has been observed in patients who have undergone intestinal resection (Jeppesen et al. 2000, Gut; Gillard et al. 2017, Front Physiol), which allows for adaptive intestinal motility and optimizes host metabolism with minimal nitrogen and energy nutrient supply. This impact is particularly pronounced on the subject's energy (fat mass) and nitrogen (lean mass and muscle mass) reserves. Therefore, improving intestinal GLP-1 secretion by administering a GLP-1-secreting probiotic is beneficial for such subjects.

[0130] According to certain embodiments, the subject to be treated (or otherwise in need thereof) is a subject who is indicated for administration of a GLP-1 receptor agonist. An individual who is indicated for administration of a GLP-1 receptor agonist is an individual suffering from a disorder or disease that can be treated or the symptoms of which can be alleviated by administering one or more GLP-1 receptor agonists to said individual.

[0131] GLP-1 receptor agonists are most often synthetic peptides whose polypeptide sequence is close to that of GLP-1, which act by binding to the GLP-1 receptor and generally have increased stability compared to endogenous GLP-1.

[0132] 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.

[0133] According to a particular embodiment, the subjects for whom administration of a GLP-1 receptor agonist is indicated are selected from insulin-resistant subjects, such as diabetic subjects and overweight subjects, in particular obese subjects, subjects who have undergone metabolic surgery, subjects for whom appetite is to be regulated, subjects suffering from liver disease, subjects suffering from cardiovascular disease, in particular subjects suffering from cardiovascular disease associated with diabetes, in particular subjects suffering from inflammation associated with diabetes and / or metabolic syndrome, subjects with sarcopenia, subjects with cachexia; and subjects suffering from a neurodegenerative disease.

[0134] "Metabolic surgery" refers to a type of surgery aimed at treating metabolic disorders through surgical methods. Metabolic surgery, also known as diabetic surgery or glycometabolic surgery, encompasses surgical procedures for controlling both diabetes and obesity. These can include surgical interventions to regulate appetite, gastric emptying, food preference, and / or taste.

[0135] An example of a liver disease for which administration of a GLP-1 agonist is indicated is non-alcoholic steatohepatitis (NASH).

[0136] Cardiovascular diseases for which administration of a GLP-1 agonist may be indicated include in particular arteriosclerosis, myocardial infarction, stroke or alterations in the lipid profile (total cholesterol, LDL cholesterol, HDL / LDL ratio).

[0137] Neurodegenerative diseases for which administration of a GLP-1 agonist may be indicated include in particular Alzheimer's disease or Parkinson's disease.

[0138] According to a particular embodiment, the subject to receive the preventive and / or therapeutic treatment is selected from elderly people with sarcopenia, overweight subjects, and obese subjects with sarcopenic obesity on a diet.

[0139] The present disclosure also describes a method for preventing and / or treating a disorder requiring an increase in the level of GLP-1 in a subject in need thereof, wherein the use is selected from (i) the prevention or treatment of a disorder associated with insulin resistance and / or dysregulation of blood glucose, and (ii) the prevention or treatment of loss of muscle mass and / or loss of muscle function, characterized in that the method at least comprises administering a bacterial strain of the species Limosilactobacillus mucosae.

[0140] Furthermore, the present invention relates to the non-therapeutic use of a bacterial strain of the species L. mucosae according to the present invention or a composition comprising same for maintaining or increasing muscle mass and / or muscle function in a subject in need thereof, in particular in a subject selected from malnourished subjects, elderly subjects, in particular malnourished elderly subjects and subjects engaged in strenuous physical exercise.

[0141] Within the meaning of this specification, "malnutrition" refers to a "state of an organism in nutritional imbalance" ("Diagnosis of undernutrition in children and adults—Method recommendations for clinical practice" November 2019, National Health Authority and French Nutrition Federation), where the imbalance is characterized by an impaired balance of energy and / or protein. This definition encompasses multiple circumstances that can result in a state of nutritional deficiency, such as a deficiency in an individual's nutrient intake, or increased consumption or loss leading to an imbalance. The term also covers subjects with increased nutritional needs. The imbalance inherent in nutritional deficiency has a detrimental effect on the body, with measurable changes in bodily function and / or body composition, and these changes can be associated with worsening the progression of diseases that may affect the subject.

[0142] "Elderly subject" is as defined above.

[0143] "Intense physical exercise" refers to physical activity requiring great effort that causes shortness of breath and elevated heart rate. Intense physical activity is characterized by a Metabolic Equivalent of Task (MET) greater than 6 (1 MET is equivalent to 3.5 mL of oxygen intake per minute per kg of body weight). The MET represents the ratio of energy expenditure during physical activity to energy expenditure at rest. During physical exercise, especially in insulin-resistant subjects, GLP-1 can be an interesting complementary strategy to help optimize glycemic control and enhance insulin sensitivity. Intense physical activity also stimulates GLP-1 production.

[0144] The present application also describes a method for maintaining or increasing muscle mass and / or muscle function in a subject in need thereof, in particular a subject selected from malnourished subjects, elderly subjects, in particular malnourished elderly subjects, and subjects engaged in strenuous physical exercise, said method comprising at least the step of administering to a subject in need thereof at least one bacterial strain of the Limosilactobacillus mucosae species.

[0145] Finally, the present invention relates to a strain of the species Limosilactobacillus mucosae deposited at the CNCM under accession number CNCM I-5661.

[0146] The invention will now be explained in more detail using the following examples, given by way of illustration.

[0147] Example

[0148] 1. Selection of bacterial strains capable of secreting GLP-1

[0149] Sixty-one strains of Lactobacillus derived from the feces of gnotobiotic animals previously transplanted with feces from patients with short bowel syndrome were tested. These Lactobacillus strains are abundant in the feces of patients with short bowel syndrome and have a strong tropism for the gut, as they are able to colonize the gastrointestinal tract of axenic rats.

[0150] We sequenced the 16S gene, divided the isolates into six species, and characterized them morphologically, phenotypically, and genomically by selecting one to two isolates per species for a total of seven strains.

[0151] The six species are as follows: Lacticaseibacillus casei (strain 1 and strain 2), Lacticaseibacillus camelliae (strain 3), Ligilactobacillus salivarius (strain 4), Lacticaseibacillus rhamnosus (strain 5), Limosilactobacillus reuteri (strain 6), Limosilactobacillus mucosae (strain CNCM I-5661, also known as strain I-5661)

[0152] The strain was characterized by functional tests at the INRAE ​​in Aurillac (Unite Mixte de Recherche sur le Fromage Aurillac, UMR 0545).

[0153] All of the strains isolated above were cultured in enteric neuroendocrine cells from SCT-1 mice. 10 9 2x10 bacteria 6 After incubation with 80% confluent SCT-1 cells at 37°C and 5% CO2 for 4 hours, the cell supernatant was collected and the peptide GLP-1 in the supernatant was measured (by ELISA).

[0154] The results are presented in FIG.

[0155] Of all the strains tested, none demonstrated significant synthesis of GLP-1 in the culture medium, except for the CNCM I-5661 strain, which resulted in highly significant production of GLP-1 in the medium (P<0.05).

[0156] In fact, among all strains from the same donor, only the strain of the species L. mucosae CNCM I-5661 was able to increase GLP-1 production by 25-fold. When lactic acid bacteria of the species Lacticaseibacillus casei 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).

[0157] This strain corresponds to the species Limosilactobacillus mucosae.

[0158] The control group corresponds to the culture of enterocytes in sterile medium (no production of GLP-1).

[0159] Results of induction of GLP-1 secretion by STC-1 cells

[0160] The STC-1 cells were obtained from the ATCC collection (reference number STC-1, CRL-325 商標 ) and were grown and prepared for their co-culture the day before the experiment. Bacteria, frozen in dry pellets, were thawed on the day of the experiment and incorporated into culture medium without FCS or antibiotics. They were prepared by serial dilution to achieve MOIs (multiplicities of infection) of 1:10, 1:100, and 1:1000.

[0161] The STC-1 cells were washed, and the medium containing the bacteria was then added. After 4 hours of co-culture, the supernatant was collected and counted. The supernatant, along with the cells, was then stored at -80°C for subsequent GLP-1 measurement. The amount of GLP-1 was measured by ELISA according to the supplier's instructions (ELISA GLP-1 Mouse (Reference No.: MOFI00854)).

[0162] GLP-1 production is expressed in pg / ml.

[0163] The definitions of the terms used in Table 1 below are as follows: Control: STC-1 cells in the presence of culture medium MOI: 10 (number of bacteria added per STC-1 cell) C: CNCM-I5661 bacteria were cultivated in MRS medium (supplier BD, reference number 288130, reconstituted according to the supplier's instructions), then centrifuged and frozen in the form of a dry pellet, which was then resuspended in STC cell culture medium. V: CNCM-I5661 bacteria were cultivated in "veganMRS" medium (supplier BIOKAR, reference number BK176HA, reconstituted according to the supplier's instructions), then centrifuged and frozen in the form of a dry pellet, which was then resuspended in STC-1 cell culture medium. 61C-10: Incubation of STC-1 cells in the presence of the CNCM-I5661 strain. MOI: 10 (10 times the number of bacteria per STC-1 cell). 61C-100: Incubation of STC-1 cells in the presence of the CNCM-I5661 strain. MOI: 100 (100 times the number of bacteria per STC-1 cell). 61C-1000: Incubation of STC-1 cells in the presence of the CNCM-I5661 strain. MOI: 1000 (1000 times the number of bacteria per STC-1 cell).

[0164] [Table 1]

[0165] The results shown in the table above demonstrate the dose effect of the strain and also show that it maintains its functionality when grown in different media.

[0166] Conclusion: The presence of strain CNCM-5661 induces the production of the intestinal hormone GLP-1 by STC-1 cells. This production becomes more significant as the bacterial population increases. This production is not observed in the presence of a strain of Lacticaseibacillus casei derived from the same patient. The effect of pro-GLP-1 from strain CNCM-5661 is independent of the medium used for its cultivation.

[0167] Moreover, the inventors showed that the production of GLP-1 increased as a function of the contact time between bacteria of the CNCM I-5661 strain and intestinal cells (see Figure 2).

[0168] 2. Survival ability of CNCM I-5661 strain in the intestinal environment

[0169] Various tests were performed to determine whether the CNCM I-5661 strain could survive in the intestinal environment.

[0170] Bacterial resistance to gastric (stomach) acidity

[0171] Bacteria were placed in acidic medium (pH 2.5 and 3) for 45 and 90 minutes, which corresponds to the average residence time of a food bolus in the stomach before entering the duodenum.

[0172] The bacteria showed very good resistance to gastric medium (composition: HCl, pepsin, NaCl), and there was no significant difference between the incubation time and the two pH values ​​tested (p>0.05, Fisher exact test).

[0173] The results are presented in Table 2 below.

[0174] [Table 2]

[0175] Bacterial resistance to stomach acid (bile salts)

[0176] We also tested the survival of bacteria under conditions encountered downstream of the stomach, including the presence of bile salts. Therefore, the viability of the CNCM I-5661 strain was tested in the presence of bile salts after 1, 2, 3, and 4 hours of incubation at 37°C.

[0177] The bacteria showed very good resistance to bile salts, with no significant difference between the incubation times (p>0.05, Fisher exact test).

[0178] The results are presented in Table 3 below.

[0179] [Table 3]

[0180] 3. Adhesion ability of CNCM I-5661 strain to intestinal cells

[0181] Finally, to estimate the probiotic potential of the CNCM I-5661 strain, we determined its ability to adhere to human intestinal Caco-2 cells. The viable count of lactic acid bacteria adhering to intestinal cells was determined after 3 hours of contact with Caco-2 cells at multiplicity of infection (MOI) values ​​of 0.1, 1, 10, and 100.

[0182] The CNCM I-5661 strain showed a satisfactory percentage of adhesion, similar to the other microorganisms, but there was no significant difference between the MOIs tested (p>0.05, Fisher exact test).

[0183] The results are presented in Table 4 below.

[0184] [Table 4]

[0185] 4. Extension of the characteristics described for strain CNCM I-5661 to the entire Limosilactobacillus mucosae species

[0186] To determine whether the beneficial effects observed with L. mucosae CNCM I-5661 strain could be applied to other strains of the same species, the ability of other strains of the Limosilactobacillus mucosae species to enable secretion of GLP-1 by SCT-1 cells in culture was tested against other strains of the Limosilactobacillus mucosae species.

[0187] Therefore, three other strains were tested: DSM 13345, DSM 13346, and DSM 102820. The CNCM I-5661 strain (as a positive control) and the L. casei strain (negative control, which does not induce the synthesis of GLP-1) were also used. Control: sterile cell culture medium; Lacticase Bacillus casei (L. casei) strain (negative control) approx. 5.10 9 CFU / mL (strain A); Limosil Lactobacillus mucosae (L. mucosae) CNCM I-5661 (positive control) approx. 5.10 9 CFU / mL (strain B); Limosil Lactobacillus mucosae (L. mucosae) DSM 13345 (S32T) Approx. 2.10 9 CFU / mL (strain C); Limosil Lactobacillus mucosae (L. mucosae) DSM 13346 Approx. 4.10 9 CFU / mL (strain D); Limosil Lactobacillus mucosae (L. mucosae) DSM 102820 Approx. 5.10 9CFU / mL (strain E); Under "dilution" conditions, strains B through E were diluted 1 / 10.

[0188] The results shown in Figure 3 demonstrate that GLP-1 synthesis by SCT-1 cells was observed in the presence of all strains of Limosilactobacillus mucosae tested. In addition, this GLP-1 production was dose-dependent.

[0189] 5. Effect of CNCM I-5661 strain on muscle mass in a frail aged rat model

[0190] To estimate the anabolic probiotic effect on GLP-1 targets, we measured the potency of the inventive Lactobacillus mucosae strain CNCM I-5661 (shown to induce GLP-1 synthesis by SCT-1 cells in culture) and a non-inventive Lacticaceae Bacillus casei strain (which does not induce GLP-1 production) on muscle mass in a frail elderly rat model.

[0191] We conducted a one-month in vivo study on aged rats (20 months) according to the following group: ad libitum intake group (n=15); a group that consumed 75-80% of their ad libitum intake (to mimic malnutrition in the elderly, a factor in frailty) (n=16); A group (n=13) supplemented daily with CNCM I-5661 bacteria (109 CFU) at 75-80% of their ad libitum intake; and Limosilactobacillus casei strain (10 9 CFU) supplemented group (n=16).

[0192] Animals were sacrificed and weighed at the end of the experiment, and the hind leg muscles (gastrocnemius, extensor digitorum longus, soleus, and tibialis anterior) were excised and weighed. The sum of the weights of these four muscles was calculated and reduced to the animal's body weight.

[0193] The results are presented in Figure 4, which shows that supplementation with L. mucosae CNCM-I5661 alone enabled restricted rats to increase muscle mass compared with animals fed an ad libitum diet (P = 0.01) and a restricted diet (trend, P = 0.092).

[0194] Furthermore, muscle mass was comparable in the AL, R, and R+L casei groups, suggesting that L. casei, unlike L. mucosae CNCM-I5661, did not increase muscle mass, suggesting the specific effect of L. mucosae CNCMI-I5661, unlike other lactobacilli, in increasing muscle mass in a frail aged rodent model.

Claims

1. A bacterial strain of the species Limosilactobacillus mucosae, or a lysate or culture supernatant thereof, for use in the prevention and / or treatment of a disorder requiring increased production of GLP-1 in a subject in need of such prevention and / or treatment, wherein the disorder is selected from (i) disorders associated with impaired insulin sensitivity and / or blood glucose regulation, and (ii) loss of muscle mass and / or loss of muscle function.

2. 2. The bacterial strain for use according to claim 1, characterized in that the subject in need is a subject who exhibits an indication for the administration of a GLP-1 receptor agonist.

3. 3. The bacterial strain for use according to claim 2, characterized in that the subjects for whom administration of a GLP-1 receptor agonist is indicated are selected from the list consisting of insulin-resistant subjects, such as diabetic subjects and overweight subjects, in particular obese subjects, subjects who have undergone metabolic surgery, subjects for whom appetite is to be regulated, subjects suffering from liver disease, subjects suffering from cardiovascular disease, in particular subjects suffering from cardiovascular disease associated with diabetes, subjects suffering from inflammation, in particular inflammation associated with diabetes and / or metabolic syndrome, subjects with sarcopenia, subjects with cachexia; and subjects suffering from a neurodegenerative disease.

4. 4. The bacterial strain for use according to any one of claims 1 to 3, characterized in that the disorder is a disorder associated with impaired insulin sensitivity and / or glycemic control selected from prediabetes, type 1 diabetes and type 2 diabetes.

5. 4. The 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 muscle function and that the subject in need is selected from elderly subjects with sarcopenia, overweight and obese subjects with diet-treated sarcopenic obesity, diabetic or pre-diabetic subjects and / or subjects with cachexia, in particular subjects associated with cancer, inflammatory bowel disease or chronic obstructive pulmonary disease, immobilization, "severe burn" conditions, subjects suffering from sepsis or viral infections, in the recovery phase and / or immobilization and / or those diseases associated with bowel resection or intestinal malabsorption.

6. 6. The bacterial strain for use according to any one of claims 1 to 5, characterized in that the bacterial strain is selected from the strain of the species Rimosyl Lactobacillus mucosae deposited at the CNCM under accession number CNCM I-5661, the strain of the species Rimosyl Lactobacillus mucosae deposited at DSM under accession number DSM 13345, the strain of the species Rimosyl Lactobacillus mucosae deposited at DSM under accession number DSM 13346, the strain of the species Rimosyl Lactobacillus mucosae deposited at DSM under accession number DSM 102820, or a combination thereof, in particular the strain of the species Rimosyl Lactobacillus mucosae deposited at the CNCM under accession number CNCM I-5661.

7. A bacterial strain for use according to any one of claims 1 to 6, characterized in that the bacterium of the species L. mucosae is in live or dead form, preferably in live form.

8. 8. The bacterial strain for use according to any one of claims 1 to 7, characterized in that the bacterial strain is comprised in a composition comprising a physiologically acceptable medium, in particular in an oral composition, more in particular in an oral composition selected from the group consisting of foods, beverages, pharmaceuticals, nutraceuticals, food additives, food supplements, dairy products and live biotherapeutic products (LBPs).

9. The composition may further comprise one or more other probiotic bacterial strains, in particular Bifidobacterium longum species, Bifidobacterium lactis species, Bifidobacterium breve species, Bifidobacterium infantis species, Bifidobacterium adolescentis species, Lactobacillus acidophilus species, Lactobacillus casei species, Lactobacillus salivarius species, Lactobacillus johnsonii species, Lactobacillus salivarius species, Lactobacillus salivarius species, Lactococcus lactis species, Enterococcus faecium species, Enterococcus faecalis species, Saccharomyces cerevisiae species, Saccharomyces boulardii species, Faecalibacterium prausnitzii species, Akkermansia muciniphila species, Blautia faecis species, Faecalibacterium prausnitzii species, Streptococcus thermophilus one or more other probiotic bacterial strains selected from the group consisting of Bifidobacterium longum NCC3001 (ATCC 94949), ...BAA-999), Bifidobacterium longum NCC2705 (CNCM I-2618), Bifidobacterium longum NCC490 (CNCM I-2170), Bifidobacterium lactis NCC2818 (CNCM I-3446), Bifidobacterium breve strain A, Lactobacillus johnsonii NCC533 (CNCM I-1225), Enterococcus faecium SF 68 (CNCM I-1226), Bifidobacterium lactis NCC2818 (CNCM I-3446), Bifidobacterium breve strain A (CNCM I-1226), Bifidobacterium longum NCC2705 (CNCM I-2618), Bifidobacterium longum NCC490 (CNCM I-2170), Bifidobacterium lactis NCC2818 (CNCM I-3446), Bifidobacterium breve strain A (CNCM I-1226), Bifidobacterium breve strain B (CNCM I-1226), Bifidobacterium breve strain C (CNCM I-1226), Bifidobacterium breve strain D (CNCM I-1226), Bifidobacterium breve strain E (CNCM I-1226), Bifidobacterium breve strain F ... 68) (NCC2768; NCIMB10415), Lactobacillus casei (CNCM I-5662 and CNCM I-5663), Streptococcus thermophilus (CNCM I-5334), and combinations thereof.

10. A bacterial strain for use according to claim 8, characterized in that the composition does not contain any other bacteria of the Lactobacillus genus.

11. A 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 a bacterial strain of the species Limosilactobacillus mucosae or a lysate or culture supernatant thereof according to any one of claims 6 to 11, for maintaining or increasing muscle mass and / or muscle function in a subject in need thereof, in particular a subject selected from malnourished subjects, elderly subjects, in particular malnourished elderly subjects, and subjects engaged in strenuous physical exercise.

13. The bacterial strain Limosilactobacillus mucosae has been deposited at the CNCM under accession number CNCM I-5661.

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