WO2021255310A1

WO2021255310A1 - Strain of the bacteroides genus for use in the treatment and/or prevention of eating disorders

Info

Publication number: WO2021255310A1
Application number: PCT/ES2021/070438
Authority: WO
Inventors: Ana Agustí Feliú; Isabel CAMPILLO NUEVO; Yolanda Sanz Herranz; Vicente Felipo Orts; Tiziano BALZANO
Original assignee: Consejo Superior De Investigaciones Cientificas (Csic); Centro De Investigación Príncipe Felipe
Priority date: 2020-06-17
Filing date: 2021-06-15
Publication date: 2021-12-23
Also published as: ES2886646A1; ES2886646B2

Abstract

The present invention relates to a strain of the Bacteroides genus, preferably the B.uniformis CECT 7771 strain, for use in the prevention of or reduction in the risk of, and in the treatment of, subclinical or clinical forms of eating behaviour disorders such as hyperphagia, binge-eating disorder, addictive or selective consumption of food, bulimia nervosa, anorexia nervosa, the anxiety associated with disturbances in eating behaviour, and megarexia. The present invention also relates to a composition comprising said strain for the above use.

Description

DESCRIPTION

Strain of the genus Bacteroides for use in the treatment and / or prevention of eating disorders

The present invention relates to a bacterium of the genus Bacteroides and, more specifically, of the species and strain B. uniformis CECT 7771 for use in the prevention, risk reduction and / or treatment of sub-clinical or clinical forms of eating disorders, including excessive eating or hyperphagia, binge eating disorder, addictive or selective food intake, bulimia nervosa and anorexia nervosa, among others. The present invention falls within the field of therapeutic activity of pharmaceutical compositions or preparations, as well as within the field of food. BACKGROUND OF THE INVENTION

Eating disorders are characterized by a lack of control over food intake. These alterations can lead to an increase in intake and, therefore, contribute to obesity and its complications, as well as lead to compulsive or addictive behavior, contributing to the development of mental pathologies. Its origin is complex, involving biological, psychological and sociocultural factors and, therefore, also its treatment and prevention.

Eating disorders, related to excessive and / or uncontrolled food consumption, are increasing and show a prevalence that varies from 5% in the general population to more than 40% in obese individuals, which aggravates the consequences obesity (Lemeshow AR, et al. Eat BehavDec; (2016) 23: 110-114). These eating behavior disorders are also associated with other mental disorders, with substance abuse, and often present together (for example, bulimia and alcohol abuse), increasing the dimension of the problem (Munn-Chernoff MA, et al. Addict Biol. (2020) Feb 16: e12880. Doi: 10.1111 / adb.12880). These associations suggest that these mental pathologies may have a common etiopathological substrate. In addition, epidemiological studies have associated alterations in eating behavior with other disorders psychiatric such as anxiety, among others (Levin BE. Am J Physiol. (1996) Feb; 270 (2 Pt 2): R456-61).

Two components are involved in controlling food intake: homeostatic aspects related to energy balance and hedonic aspects, related to the sensation of pleasure or reward caused by food intake. The main objective of the homeostatic component is to meet the energy needs to maintain the vital functions of the body. Different hormones that are produced in the gastrointestinal tract and peripheral tissues, such as glucagon-like peptide-1 (GLP-1), insulin, ghrelin, leptin, cholecystokinin or peptide YY regulate energy balance and the sensation of hunger or satiety (Cummings, DE and J. Overduin. J Clin Invest, (2007) 117 (1), 13-23). At the level of the central nervous system, the hypothalamus is one of the most important brain areas for the regulation of food intake in the short and long term through the synthesis of orexigenic neuropeptides, such as neuropeptide Y (NPY) and the “agouti-related peptide ”(AgRP), and anorectic neuropeptides, such as the transcript regulated by cocaine and amphetamines (CART) and propiomelanocortin (POMC), among others (Arora, S. and Anubhuti, Neuropeptides, (2006) 40 (6), 375-401). Among the components that regulate the hedonic aspect of food intake, one of the main ones is the dopaminergic system. The main neurotransmitter associated with the reward response in the mesolimbic system is dopamine (DA) and it is crucial for the "desire" to eat food (Tindell, AJ, et al. Eur J Neurosci, (2005) 22 (10), 2617-34). DA neurons project to the striatum, cortex, hypothalamus, and limbic system, including the nucleus accumbens (NAc), and regulate different physiological functions, including hormone secretion, as well as motivation and emotions (Tritsch, NX, and Sabatini, BL , Neuron (2012) 76, 33-50). The study of the neurobiology of the reward circuit has focused on the NAc since most drugs of abuse release DA in the NAc each time they are taken (Wise, RA, et al., Psychopharmacology (Berl), (1995 ) 120 (1), 10-20) and a similar effect has been observed in animal models that are fed tasty or appetizing foods (Bassareo, V. and G. Di Chiara, Eur J Neurosci, (1999) 11 (12) , 4389-97).

Scientific evidence indicates that there is a two-way communication between the gut and the brain (called the gut-brain axis) that is regulated by signals hormonal, immunological and neural. The intestinal microbiota acts as a regulator of the so-called gut-brain axis and, through interactions with diet, and influences the central nervous system and behavior, as has been shown in intervention studies with probiotics or antibiotics that modify the microbiota, especially in experimental animals (Rodgers RJ Pharmacology Biochemistry and Behavior (2010) 97 (1), 3-14). Regarding its role in regulating the homeostatic component that regulates intake, some studies suggest that the intestinal microbiota and the metabolites produced by it (short-chain fatty acids) can stimulate the production of gastrointestinal hormones, such as GLP-1 and the PYY, and reduce appetite in the short term (Cummings, DE and J. Overduin. J Clin Invest (2007) 117 (1), 13-23). However, its possible role in controlling the hedonic aspects of eating, as well as in mental complications associated with eating disorders, is largely unknown. Due to the continuous increase in the prevalence of eating behavior disorders, it is necessary to continue with the search for effective preventive and therapeutic strategies. These may be based on new bacterial strains, which are part of the intestinal microbiota of healthy individuals, and on their active molecules, which mediate the gut-brain relationship and which can act on neural pathways involved in the control of the hedonic component and the systems of reward that regulate food intake, as proposed in the present invention.

DETAILED DESCRIPTION OF THE INVENTION The present invention relates in a first aspect to a bacterial strain of the genus Bacteroides (hereinafter, strain of the invention), or to a strain derived from it, for use in prevention, risk reduction and / or or the treatment of sub-clinical and clinical forms of eating disorders. In a more preferred embodiment, the bacterial strain for use is a strain of the spice B. uniformis.

In an even more preferred embodiment, the bacterial strain for use is the B. uniformis CECT 7771 strain. Eating disorders are disorders derived from a lack of control over food intake, including hyperphagia or excess ingestion, binge eating disorder, addictive or selective food intake, bulimia nervosa and anorexia nervosa, among others.

In a preferred embodiment of the invention, the eating disorder is selected from the list comprising: excessive eating or hyperphagia, binge eating disorder, addictive or selective food intake, bulimia nervosa, anorexia nervosa, associated anxiety alterations in eating behavior and megarexia.

The inventors have discovered that the genus Bacteroides and more specifically the species B. uniformis and the strain B. uniformis CECT 777 exhibit the ability to reduce total calorie intake and the amount of solid food in the form of bingeing in an animal model. Binge eating episodes (excessive eating in a short period of time) are characteristic of hyperphagia, the so-called binge eating disorder, addictive or selective food intake and bulimia nervosa and also occur in anorexia nervosa, in The one that can alternate periods of fasting with specific episodes of ingestion in the form of binge eating. This effect has been demonstrated (as shown in the examples provided in the invention) by administering the B. uniformis CECT 7771 strain orally to an animal model in which loss of control of intake is induced and binge eating by introducing intermittent periods of fasting and subsequent exposure to normal food and / or tasty food (for example, high in sugars such as sucrose). Studies have shown that at the end of the protocol (18 days) the experimental group that has received the vehicle eats more total calories in the binge period than the experimental group that has been treated with B. uniformis CECT 7771, which attenuates this alteration in the intake. It has also been observed that the administration of B. uniformis CECT 7771 during the study reduces, especially, the intake of solid food in the form of bingeing, since while in the group that received the vehicle, the intake of solid food significantly increased between the On day 2 and day 18, in the group that received the CECT 7771 strain, no significant increase was observed, suggesting that this bacterium attenuates the increase in solid food intake induced by intermittent fasting (Example 1, Figure 1B).

The inventors have also shown that a strain of the genus Bacteroides reduces anxiety associated with alterations in the control of food intake, both in the period of activity and, therefore, in the search for food and ingestion (at night), and in the period of rest (light). Specifically, the inventors have shown that the bacterium B. uniformis CECT 7771, whose use is the object of the invention, reduces the number of entries to the light zone in the light-dark test, which are increased in the model that receives the vehicle, indicating that it reduces anxiety and risky behavior during the period of activity.In addition, it is shown that the administration of the bacterium B. uniformis CECT 7771 reduces the latency time to come into contact with food, which is increased in the model , by means of the anxiety test against hunger carried out in the rest period. (Example 2, Figure 2D).

As demonstrated in the present invention, the use of the bacterium B. uniformis CECT 7771 makes it possible to restore the expression of dopamine receptors in the prefrontal cortex of the brain (D1 R) and in the intestine (D1 R and D2R). The improvement of dopamine signaling at the level of the enteric and central nervous system, through the normalization of the expression of these receptors, constitutes a regulatory mechanism of the reward system, which may explain the reduction of the intake in the form of binge eating, such as result of the administration of the bacteria. Additionally, the use of the bacterium B. uniformis CECT 7771 allows to reestablish some of the alterations caused by intermittent fasting in the intestinal microbiota, such as the reduction of the abundance of Muribaculum spp. since their concentrations are normalized when administering the bacterium object of the patent. Furthermore, the administration of B. uniformis CECT 7771 increases the prevalence and abundance of this and other bacterial species (Akkermanisa muciniphila and Christensenella minuta) that may explain its beneficial effects on food intake and anxiety (Example 4, Figure 5).

Within the scope of the present invention, the strain B. uniformis CECT 7771 refers to a strain isolated from infant feces, identified and deposited in the Spanish collection of type cultures (CECT) on July 21, 2010 and to which it corresponded the CECT deposit number 7771. The address of said International Depository Authority is: University of Valencia Bujassot Campus Research Building 46100 Burjassot (Valencia).

Within the scope of the invention, it is possible to use a strain derived from the strain B. uniformis CECT 7771, where said strain maintains or improves the capabilities described throughout the present invention. The derived microorganism can be produced naturally or intentionally, by means of mutagenesis methods known in the state of the art, such as, for example, but not limited to, the growth of the original microorganism in the presence of mutagenic or stress-causing agents, modifying the growing conditions (eg, increasing aeration or exposure to oxygen, pH, or temperature) or by genetic engineering aimed at modifying specific genes. According to a preferred embodiment, a strain derived from the strain B. uniformis CECT 7771 generated by adaptation to the environment or by directed genetic modification is used. The terms "mutant strain" or "derived strain" can be used interchangeably.

The strain B. uniformis CECT 7771 or any mutant or derivative thereof, can be used in any way that exerts the effects described, such as, for example, according to a preferred embodiment of the present invention, the strain B. uniformis CECT 7771 is in the form of viable cells (cultivable or non-culturable), or according to another preferred embodiment of the invention, the strain is in the form of non-viable cells ("dead" cells inactivated by any technique known in the state of the art, such as, for example, but without limitation, heat, freezing, mechanical or chemical disruption or ultraviolet radiation).

The present invention also contemplates the combination of cellular components, metabolites, secreted molecules or any of their combinations, obtained from strain CECT 7771 for use in the treatment (in sub-clinical or clinical forms) and / or in risk reduction and prevention of eating disorders.

Cellular components of the bacterium could include cell wall components (such as, but not limited to, peptidoglycan), nucleic acids, membrane components, or others such as proteins, lipids, and carbohydrates, and their combinations, such as lipoproteins, glycolipids or glycoproteins. Metabolites include any molecule produced or modified by the bacterium as a consequence of its metabolic activity during its growth, its use in technological processes (for example, but not limited to, food or drug manufacturing processes), during product storage or during gastrointestinal transit. Examples of these metabolites are, but are not limited to, organic and inorganic acids, proteins, peptides, amino acids, enzymes, lipids, carbohydrates, lipoproteins, glycolipids, glycoproteins, vitamins, salts, metals, or nucleic acids. Secreted molecules include any molecule exported or released abroad by the bacterium during its growth, its use in technological processes (for example, food or drug manufacturing), product storage or gastrointestinal transit. Examples of these molecules are, but are not limited to, organic and inorganic acids, proteins, peptides, amino acids, enzymes, lipids, carbohydrates, lipoproteins, glycolipids, glycoproteins, vitamins, salts, metals, or nucleic acids.

A second aspect of the invention relates to a composition, hereinafter "composition of the invention", comprising a strain of the genus Bacteroides, more preferably of the species Bacteroides uniformis and even more preferably the strain B. uniformis CECT 7771, a strain derived from it and / or the cellular components, metabolites, secreted molecules of the strain or any of their combinations for use in the prevention, risk reduction and / or treatment of sub-clinical or clinical forms of disorders of the eating behavior.

Preferably, the eating disorders are those described in the first aspect of the invention.

In a preferred embodiment, the composition of the invention for use has a concentration of the strain of the invention of between 10 ⁴ and 10 ¹⁴ colony forming units (ufe) per gram or milliliter of final composition.

The composition of the invention for its use may further comprise at least one other additional microorganism other than the B. uniformis CECT 7771 strain and / or its cellular components, metabolites or secreted molecules, or any combination thereof. For example, but not limited to, the additional microorganism that can be part of said composition is selected from at least one of the following groups:

- at least one strain of another species of the genus Bacteroides and, especially, or of the species Bacteroides uniformis;

- at least one lactic bacteria or bifidobacteria of intestinal, food or environmental origin. Lactic acid bacteria is selected from the list comprising, but not limited to, a bacterium of the genus Bifidobacterium, Lactobacillus, Lactococcus, Enterococcus, Propionibacterium, Leuconostoc, Weissella, Pediococcus or Streptococcus;

- at least one strain of other phylogenetic groups, genera or species of prokaryotes of intestinal, alimentary or environmental origin, such as for example but not limited to Archaea, Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Verrucomicrobia, Fusobacteria, Metanobacteria, Spirochaetes, Fibrobacteres,

Deferribacteres, Deinococcus, Thermus, Cyanobacteria, Methanobrevibacterium, Peptostreptococcus, Ruminococcus, Coprococcus, Subdolingranulum, Dorea, Bulleidia, Anaerofustis, Gemella, Roseburia, Catenibacterium, Dialister, Anaerloterococcus, Bacteriaceae, Bacteriaceae, Probacteriaceae, Stabacteriaceae, Stabacteriaceae, Propibacotelium, Eubacterium, Akkermansia, Bacillus, Butyrivibrio, Christensenella or Clostridium;

- at least one strain of fungus or yeast, such as, for example, but not limited to, belonging to the genus Saccharomyces, Candida, Pichia, Debaryomyces, Torulopsis, Aspergillus, Rhizopus, Mucor or Penicillium.

Said additional microorganism can be a strain of the same species or of a different species or taxonomic group of microorganisms from the one corresponding to the strain of the invention. The cells that comprise the composition can be non-viable or viable and be in any phase of the state of development or growth (latent, exponential, stationary, etc.), regardless of the morphology they present. In a particular embodiment, said additional microorganism comprises at least one intestinal bacteria or a lactic bacteria. Optionally, in another particular embodiment, the composition of the invention for use may also comprise at least one bioactive component (active substance, active principle or therapeutic agent), such as, for example, components of food, plant products and / or drugs. The term "bioactive component" refers to a compound with biological activity within the scope of the patent that can improve or complement the activity of the Bacteroides strain of the invention (preferably B. uniformis CECT 7771), including ingredients or components of food (for example and without limitation: polyunsaturated fatty acids, conjugated linoleic acid, prebiotics, fiber, Guar gum, glucomannan, chitosan, copper picolinate, calcium, etc.), other probiotics, plants, extracts or plant components and drugs. In a particular embodiment, the composition of the invention is a pharmaceutical composition. The pharmaceutical composition is a set of components that is made up of at least the strain of the invention in any concentration; or at least by the cellular components, metabolites, secreted molecules of the strain of the invention or any of its combinations, which has at least one application in the improvement of the physical or physiological or psychological well-being of a subject, which implies an improvement of the state general health or disease risk reduction. Said pharmaceutical composition can be a medicine.

The term drug has a more limited meaning than the meaning of "pharmaceutical composition", as defined in the present invention, since the drug necessarily implies a preventive or therapeutic effect. The medicine to which the present invention refers can be for human or veterinary use. The "medicine for human use" is any substance or combination of substances that is presented as having properties for the treatment or prevention of diseases in humans or that can be used in humans or administered to humans in order to restore, correct or modify the physiological functions by exerting a pharmacological, immunological or metabolic action, or to establish a medical diagnosis. The "medicine for veterinary use" is any substance or combination of substances that is presented as having curative or preventive properties with respect to animal diseases or that can be administered to the animal in order to restore, correct or modify its physiological functions by exercising a pharmacological, immunological or metabolic action, or to establish a veterinary diagnosis. Also considered "veterinary drugs" are "premixes for medicated feed" prepared to be incorporated into a feed.

In addition to the requirement of therapeutic efficacy where said pharmaceutical composition may necessitate the use of other therapeutic agents, there may be additional rationale that strongly compel or recommend the use of a combination of a compound of the invention and a biactive component, where a said bioactive component is attributed an appropriate activity to constitute a medicine. Said compound of the invention obviously refers to the strain of the invention, or to the strain derived from it, or to the cellular components, metabolites, secreted molecules or any of their combinations, obtained from the strain of the invention.

In a particular embodiment, the composition of the invention for use comprises at least one pharmaceutically acceptable carrier and / or excipient.

The "vehicle" or carrier is preferably an inert substance. The function of the vehicle is to facilitate the incorporation of other compounds, to allow a better dosage and administration or to give consistency and shape to the pharmaceutical composition. Therefore, the vehicle is a substance that is used in the medicine to dilute any of the components of the pharmaceutical composition of the present invention to a certain volume or weight; or that even without diluting said components it is capable of allowing a better dosage and administration or giving consistency and shape to the medicine. When the presentation form is liquid, the pharmaceutically acceptable carrier is the diluent.

The term "excipient" refers to a substance that helps the absorption of any of the components of the composition of the present invention, stabilizes said components or helps the preparation of the pharmaceutical composition in the sense of giving it consistency or providing flavors that make it more enjoyable. Thus, excipients could have the function of keeping the components together such as starches, sugars or celluloses, a sweetening function, a coloring function, a protective function of the drug, such as for example to isolate it from air and / or humidity, a function filling of a tablet, capsule or any other form of presentation such as, for example, dibasic calcium phosphate, disintegrating function to facilitate the dissolution of the components and their absorption in the intestine, without excluding other types of excipients not mentioned in this paragraph. Therefore, the term "excipient" is defined as that material that, included in the galenic forms, is added to the active principles or their associations to enable their preparation and stability, modify their organoleptic properties or determine the physicochemical properties of the pharmaceutical composition and its bioavailability. The "pharmaceutically acceptable" excipient must allow the activity of the compounds of the pharmaceutical composition, that is, it must be compatible with said components. Furthermore, as understood by the person skilled in the art, the excipient and the vehicle must be pharmacologically acceptable, that is, that the excipient and the vehicle are allowed and evaluated in such a way that it does not cause harm to the organisms to which it is administered. The pharmaceutical composition or drug of the invention for use can be presented in any clinically permitted form of administration and in a therapeutically effective amount. For example, it may be in a form adapted for oral, sublingual, nasal, intracatecal, bronchial, lymphatic, rectal, transdermal, inhaled or parenteral administration, preferably in a form adapted for oral administration. The pharmaceutical composition of the invention can be formulated in solid, semisolid, liquid or gaseous forms, such as tablet, capsule, powder, granule, ointment, solution, suppository, injection, inhalant, gel, microsphere or aerosol. The form adapted for oral administration is selected from the list that includes, but is not limited to, drops, syrup, herbal tea, elixir, suspension, extemporaneous suspension, drinkable vial, tablet, capsule, granule, seal, pill, tablet, lozenge, troche. or lyophilized. In a particular embodiment, the composition of the invention for use is presented in a form adapted for oral, sublingual, nasal, bronchial, lymphatic, rectal, transdermal, inhaled or parenteral administration. In a more particular embodiment, the pharmaceutical composition of the invention for use is presented in a form adapted for oral administration. The form adapted for oral administration refers to a physical state that can allow its oral administration. Said form adapted for oral administration is selected from the list that includes, but is not limited to, drops, syrup, herbal tea, elixir, suspension, extemporaneous suspension, drinkable vial, tablet, capsule, granulate, seal, pill, tablet, lozenge, troche. or lyophilized.

The "galenic form" or "pharmaceutical form" is the arrangement to which the active principles and excipients are adapted to constitute a medicine. It is defined by the combination of the form in which the pharmaceutical composition is presented by the manufacturer and the form in which it is administered.

In the present invention, the term "therapeutically effective amount" refers to that amount of the component of the pharmaceutical composition that when administered to a mammal, preferably a human, is sufficient to produce prevention and / or treatment, such as defined later, of a disease or pathological condition of interest in the mammal, preferably a human. The therapeutically effective amount will vary, for example, according to the activity of the strain of the invention; of the cellular components, metabolites, secreted molecules or any of their combinations, in any form of presentation; the therapeutically effective amount will also vary according to the metabolic stability and duration of action of the compound; the age, body weight, general health, sex and diet of the patient; the mode and time of administration; the rate of excretion, the combination of drugs; the severity of the particular disorder or pathological condition; and the subject undergoing therapy, but can be determined by a person skilled in the art based on his or her own knowledge and that description.

Alternatively to the pharmaceutical composition, the composition of the invention for use can also be a nutritional composition. The term "nutritional composition" of the present invention refers to that food or component of foods that, regardless of providing nutrients to the subject who takes it, beneficially affects one or more functions of the body, so that it provides a better state health and wellness. As a consequence, said nutritional composition can be intended for the prevention or reduction of the risk and / or treatment of a disease or sub-clinical condition or of the factor causing a disease. Therefore, the term "nutritional composition" of the present invention can be used synonymously with functional food or food for specific nutritional purposes or medicinal food. In a particular embodiment, the nutritional composition is a food, a supplement, a nutraceutical, a probiotic or a symbiotic.

In a more particular embodiment, the food is selected from the list that comprises: dairy product, vegetable product, meat product, snack, chocolate, drink or baby food. Dairy product is selected from the list comprising, but not limited to, a product derived from fermented milk (for example, but not limited to yogurt or cheese) or non-fermented (for example, but not limited to, ice cream, butter, margarine, buttermilk ). The vegetable product is, for example, but not limited to, a cereal in any form of presentation, fermented or non-fermented. The beverage can be, but is not limited to, any fruit juice or non-fermented milk. The term "supplement", synonymous with any of the terms "dietary supplement", "nutritional supplement"; or "food supplement" is a "food ingredient" intended to supplement the diet. Some examples of dietary supplements are, but are not limited to, vitamins, minerals, botanicals, amino acids, and food components such as enzymes and glandular extracts. They are not presented as substitutes for a conventional food or as a single component of a meal or of the nutritional diet but as a complement to the diet. The term "nutraceutical" as used in the present invention refers to substances isolated from a food and used in a dosage form that have a beneficial effect on health.

The term "probiotic" as used in the present invention refers to live microorganisms that when supplied in adequate amounts promote health benefits to the host organism.

The term "symbiotic" as used in the present invention refers to those foods that contain a mixture of prebiotics and probiotics. As a general rule, they contain a prebiotic component that favors growth and / or metabolic activity and ultimately the effect of the probiotic with which it is combined, as for example and without limiting it may be the association of fructooligosaccharides, galactooligosaccharides or arabino-oligosaccharides to the bifidobacteria. Another aspect of the present invention refers to the use of the strain of the invention, of a strain derived from it, of the components derived from it or the composition of the invention, for the manufacture of a drug, a nutritional composition or A food. In the present invention, the term "treatment" refers to combating the effects caused as a consequence of a disease or pathological condition of interest in a subject (preferably a mammal, and more preferably a human) including:

(i) inhibiting the disease or pathological condition, that is, arresting its development;

(ii) alleviating the disease or pathological condition, that is, causing regression of the disease or pathological condition or its symptoms; (iii) stabilize the disease or pathological condition.

In the present invention, the term "prevention" refers to preventing the onset of the disease, that is, preventing the disease or pathological condition from occurring in a subject (preferably a mammal, and more preferably a human), in particular, when said subject has a predisposition for the pathological condition. The term risk reduction refers to reducing at least one of the causative factors of the pathological condition. In the present invention, eating disorders or alterations include, but are not limited to, hyperphagia or overeating, binge eating disorder, addictive food intake, selective eater syndrome, bulimia nervosa, anorexia nervosa, megarexia, etc. In another aspect, the present invention relates to the strain of invention, the strain derived from the strain of invention, the cellular component, metabolite, secreted molecule or any of its combinations obtained from the strain of invention, or the composition of the invention, for its use as an adjuvant in the treatment of sub-clinical or clinical conditions and / or prevention or reduction of the risk of disorders or alterations in eating behavior.

In the present invention, "adjuvant" is understood to be that compound that helps to improve the effectiveness or efficiency of other drugs for the treatment of eating disorders or alterations, which would allow reducing its dose and / or the frequency of administration or enhance its efficacy by administering a formulation of the strain of the invention with complementary mechanisms of action.

Throughout the description and claims the word "comprise" and its variants are not intended to exclude other technical characteristics, additives, components or steps. For those skilled in the art, other objects, advantages and characteristics of the invention will emerge in part from the description and in part from the practice of the invention. The following examples and figures are provided by way of illustration, and are not intended to be limiting of the present invention. BRIEF DESCRIPTION OF THE FIGURES Figure 1. Effect of B. uniformis CECT 7771 on intake (total calories, solid food and sucrose solution) during bingeing on days 2 and 18 of the experiment, and body weight in a disorder model of eating behavior. Sum of total caloric intake (kcal) (A), mean intake of solid food (g) (B), mean intake of 10% sucrose (g) (difference in the weight of the bottles before and after binge) (C), evolution of body weight (g) (D) in C rats and IF rats treated or not with B. uniformis CECT 7771. Abbreviations of the experimental groups: C, control group (n = 15), control group C-D2 on day 2 (n = 15), C-D18, control group on day 18 (n = 15), IF, rats that fasted 12 h daily and received vehicle through a probe (n = 15), IF -D2 and IF-D18, IF group on day 2 and 18 respectively (n = 15), IF + B, rats that fasted 12 h and received a daily dose of 1 X10 ⁸ CFU B. uniformis CECT 7771 by probe (n = 15 ), IF + B-D2 and IF + B-D18, IF + B rats on day 2 and 18 respectively (n = 15) The rats were weighed every week during the study period (3 weeks). Statistically significant differences compared to group C-D2 are indicated with an asterisk ( ^* ), different from C-D18 are indicated with (#), different from IF-D2 are indicated with (&), different from IF + B -D2 are indicated with ($), different from IF-D18 are indicated with (@). ^* p <0.050, ^*** p <0.0010, ### p <0.0010, & p <0.050, &&& p <0.0010, $$$ p <0.0010, @@@ p <0.0010.

Figure 2. Effect of B. uniformis CECT 7771 on anxiety in an eating behavior disorder model. Light / dark test or light / dark test (A, B, C). Number of entries in the clear area (A), Latency to move to the clear area (s) (B), Time spent in the clear area (s) (C). Effect of B. uniformis CECT 7771 on anxiety after 18 h of food deprivation in an anxiety versus hunger test (D, E). Latency to initiate contact with food (D), Latency and eat (E). Abbreviations of the experimental groups: C, control group (n = 15), IF, rats that fasted 12 h daily and received vehicle by gavage (n = 15), IF + B, rats that fasted 12 h and received a daily dose of 1 X10 ⁸ CFU B. uniformis CECT 7771 per probe (n = 15). Statistically significant differences compared to group C are indicated with an asterisk ( ^* ), different from group IF are indicated with #. ^* p <0.050, ^** p <0.010. Figure 3. Expression of dopamine D1 R and D2R receptors in PFCx and intestine in an eating disorder model. Immunohistochemistry was performed using antibodies against D1 R (A, C) or D2R (B, D). The number of D1 positive cells (A, C) and D2 positive cells (B, D) were quantified in the PFCx and small intestine. Values are the mean ± SEM of three rats per group. Abbreviations of the experimental groups: C, control group (n = 3), IF, rats that fasted 12 h daily and received vehicle by gavage (n = 3), IF + B, rats that fasted 12 h and received a daily dose of 1X10 ⁸ CFU B. uniformis CECT 7771 per probe (n = 3). Statistically significant differences compared to group C are indicated with an asterisk ( ^* ), different from group IF are indicated with (#). ^** p <0.010, ^*** p <0.0010, # p <0.050, ### p <0.0010.

Figure 4. Expression of orexigenic and anorectic neuropeptides in the hypothalamus in an eating disorder model. Effect of B. uniformis CECT 7771 on the relative expression of NPY (A), CART (B) AgRP (C), and POMC (D) in the hypothalamus in a binge and food addiction model. Abbreviations of the experimental groups: C, control group (n = 15), IF, rats that fasted 12 h daily and received vehicle by gavage (n = 15), IF + B, rats that fasted 12 h and received a daily dose of 1X10 ⁸ CFU B. uniformis CECT 7771 per probe (n = 15). Statistically significant differences compared to group C are indicated by asterisks ( ^* ). ^* p <0.050, ^** p <0.010.

Figure 5. Differences in the abundance of operational taxonomic units (OTUs) between the different experimental groups. The results of the LDA analysis and the p-values of the statistical analysis are shown. The upper four panels show OTUs that present higher abundances in the control group than in those with the eating disorder (IF and IF + B). The remaining panels show OTUs that were more abundant in the groups of animals with eating disorder (IF and IF + B) than in the controls. Statistically significant differences found in the IF + B group compared to the IF group are highlighted with a red asterisk. The color of the legend group corresponds to the following experimental groups: yellow-controls; blue: eating disorder model administered vehicle; orange: eating disorder model administered B. uniformis. The abbreviations used are the following: C, control group with free access to food; IF, group subjected to intermittent fasting as eating behavior disorder model and receiving vehicle; IF + B, group subjected to intermittent fasting as a model of eating behavior disorder and that received a daily dose of 10 ⁸ CFU of B. uniformis.

EXAMPLES

The invention will be illustrated below by means of tests carried out by the inventors, which demonstrate the effectiveness of the product of the invention.

Example 1. Effects of B. uniformis CECT 7771 on intake in a model of eating disorder.

1.1 Experimental design of the animal model and sampling Male Wistar Kyoto rats (170-200 g) from the Charles Rivers laboratories (L'Arbresle Cedex, France) were used. For 10 days, the rats adapted to the facilities and to a new light / dark schedule, advancing the clock 30 minutes each day. The new schedule consisted of 12 hours of light (from 3.30 a.m. to 3.30 p.m.) and 12 p.m. of darkness (from 3.30 p.m. to 3.30 a.m.). Then, the microbiota was homogenized by mixing the bed (sawdust) used from all the rats and it was distributed again in the different cages. The rats remained in these cages with the mixed bedding for at least 3 days. Finally, the rats were individually housed in a stainless steel cage in a temperature controlled room (23 ° C) with a relative humidity of 40-50%. Then, the rats were randomly divided into three groups (n = 14 rats per group) as follows: (1) a control group (C) that received a normal diet and water for 24 h and was administered the vehicle or placebo (10% skimmed milk), (2) group subjected to intermittent fasting to induce alteration of eating behavior (IF) that fasted for 12 h (and water ad libitum) and received a normal diet and sucrose (10%) in the drinking water for the remaining 12 h, this group was administered vehicle (10% skim milk) and (3) group subjected to fasting and treated B. uniformis CECT 7771 (IF + B), which fasted for 12 h (with water ad libitum) and received a normal diet and sucrose (10%) in drinking water for the remaining 12 h, this group was administered a daily dose of 1 x 10 ⁸ colony-forming units [CFU]) of the bacterial strain .

The experiments were carried out in strict compliance with the recommendations provided in the Guide for the Care and Use of Laboratory Animals of the University of Valencia (Central Research Support Service [SCSIE], University of Valencia, Spain), and the protocol was approved by the Ethics Committee (Approval number 2015 / VSC / PEA / 00041).

After these 3 weeks, the rats were sacrificed by cervical dislocation to obtain samples, including intestine, brain and feces.

1.2 Induction of alteration of eating behavior.

To induce binge eating and food addictive behavior, the protocol developed by Avena et al. , 2008 (Avena, N.M., et al., Physiol Behav, (2008) 94 (3): p. 309-15). Every day at 3:30 a.m., the lights went on for 12 a.m.

(3: 30-15.30 h). At 7.30 h, the bacteria or vehicle were administered with gelatin and the food and the drink were weighed with 10% sucrose. Only the control group had access to food and drink with 10% sucrose. Later, at 3.30 p.m. the lights went out. At that moment the “craving” began (4h) (15.30-19.30). The "craving" is the craving that occurs in the absence of a drug or food (as in this case). This "craving" occurs because the rats are fasting for 8 h in the light phase ("basal phase", 7.30-15.30 h) and then, in the dark phase, when the lights go off at 3.30 pm, the rats begin their "active phase" without access to food or drink with 10% sucrose for at least 4 more hours and, as a consequence, rats begin to experience withdrawal symptoms. Briefly, IF and IF + P rats fasted for 12 h (8 h with light "basal phase" plus 4 h in dark "active phase"). At 7:30 p.m., all groups had access to food and a drink containing 10% sucrose for 12 hours. The first hour of these 12 hours we call it "binge". During this hour we quantified how much they ate and how much they drank. Subsequently, the rats had free access to food and drink until 7.30 am.

1.3. Effect on intake.

The effects of B. uniformis on binge eating and 10% sucrose solution were analyzed by comparing day 2 and day 18 of the experiment. The effect of the intermittent fasting protocol on bingeing on food, on sucrose solution, or both was analyzed at the beginning (on day 2) and at the end (on day 18) of the study (Figure 1A), which demonstrates the validity of the model. . The intermittent fasting protocol caused an increase in the intake of food, sucrose and both (as expressed in g or in total calories) in both experimental groups (IF and IF + B) compared to controls from the beginning of the study. This effect increased over time, especially in rats that received vehicle, while in those that received B. uniformis CECT 7771 was attenuated. The analysis of the sum of the total caloric intake (food and drink) (Figure 1A) showed that both experimental groups that were fasting for 12 h receiving the vehicle (IF) or the bacteria (IF + B) consumed more calories during the binge (359 kcal ± 1.40, p <0.0010 and 361 kcal ± 1 .50, p <0.0010, respectively) than control rats (176 kcal ± 1.20) on the second day of the study. After 18 days of intermittent fasting and feeding routine, IF rats consumed significantly more calories (502 kcal ± 2.40, p <0.0010) than control rats (118 kcal ± 1.00) and significantly more than the second day of the experiment (p <0.0010) during binge eating (comparing the same group on day 2 versus day 18), indicating that the effect size increased throughout the study time. Likewise, IF + B rats showed a higher caloric intake (425 kcal ± 1.70, p <0.0010) than control rats (118 kcal ± 1.00) after 18 days of intervention. Within-group differences (IF + B) in caloric intake between day 2 and day 18 were also significant (p <0.001) during binge eating. However, the sum of the total caloric intake of the IF + B rats was reduced compared to the IF rats that received the vehicle (p <0.001), suggesting that B. uniformis CECT 7771 reduced caloric intake during binge eating. .

IF rats and IF + B rats ate significantly more food (Figure 1 B) during binge eating (4.80 g ± 0.40, p <0.050 and 4.94 g ± 0.32, p <0.050, respectively) than control rats (2.86 g ± 0.40) on the second day of the experiment as a result of fasting (Figure 1 B). At the end of the intervention, the IF group ate significantly more (7.03 g ± 0.73, p <0.0010) than the control rats (2.36 g ± 0.28) and significantly more than the second day of the experiment (p <0.050) during the binge, indicating that the magnitude of food intake increased throughout the study time. IF + B rats showed higher food intake (5.72 g ± 0.41, p <0.001) compared to control rats (2.36 g ± 0.28) after 18 days of intervention; however, these differences were not significant with respect to the second day of the experiment in the comparisons within the group, suggesting that the increase in food intake induced by the fasting protocol was slightly improved by the administration of B. uniformis CECT 7771. Both groups, IF and IF + B, drank significantly more sucrose solution (Figure 1 C) on the second day of the experiment (11.25 g ± 0.77, p <0.0010 and 12.71 g ± 2.34, p <0.0010, respectively) than the control rats that only drank water (2.73 g ± 0.22). After 18 days, IF and IF + B rats drank significantly more than control rats (p <0.0010) and a little more than the second day of the experiment (13.75 g ± 1.34 and 12.27 g ± 1.31, respectively). No significant differences were detected in the intake of sucrose solution between the IF and IF + B groups.

We did not find any effect on the body weight of the rats throughout the 3 weeks of the experiment (Figure 1 D), possibly due to the short duration of the test.

Example 2. Effects of B. uniformis CECT 7771 on anxiety in an animal model of eating disorder. 2.1. Light / Dark test (Liqht / Dark test).

This test is based on a conflict between innate aversion to lighted areas and spontaneous exploratory behavior in a novel setting. It consists of a light-dark box made of plexiglass (44 c 44 c 40 cm). The dark compartment is one-third of the box with black walls, in which two-thirds is the light compartment with white walls. The box was illuminated with 300 lux and an open door (10 c 7.5 cm) communicating the light and dark compartments. During the dark phase (active phase), the rats were individually placed in the dark box (20 lux) and allowed to freely explore the entire box (light and dark) for 10 minutes and recorded with a video camera (Sony EXview FIADCCDII, Cornellá (Barcelona), Spain). Latency to get out of the dark side of the box (four legs on the light side), visits to the light compartment, and time spent there are measures of anxiety. All these parameters were measured and comparatively analyzed (Panlab, Barcelona, Spain). This test was performed during the dark phase (active phase). 2.2. Anxiety versus hunger test.

This test measures rat anxiety versus hunger motivation in an open field (OP). It is based on the conflict between neophobia / anxiety and hunger. To perform this test, the rats fasted for 18 hours (Control, IF and IF + B) with access to water ad libitum. During the light phase, the rats were individually placed in a corner of a white OP (45 x 90 x 60 cm) gelatin was placed in the center of the OP (the same that was used to administer B. uniformis). The OP was illuminated with 500 lux (laboratory light). Rats were observed and recorded (Sony EXview FIADCCDII, Cornellá, Barcelona, Spain) for 8 minutes and different parameters were analyzed, including latency (time) to initiate contact with food and incidence of ingestion. At the end of each experiment, the animals were returned to their cages and feeding ad libitum. All these parameters were measured and analyzed comparatively (Panlab, Barcelona, Spain). The OP was washed after each animal with 5% ethanol. 23. Effect on anxiety in the two behavior tests.

Anxiety behavior was evaluated with two different behavioral tests: the light / dark test or the light / dark test (Figure 2 A, B, C) and the anxiety versus hunger test (Figure 2 D, E). The light / dark test was performed during the dark fast or "craving", which means that the rats fasted for about 10 h (8 h during the light phase + approximately 2 h during the dark phase). Therefore, the behavioral alterations shown by this test could be due to the fact that under food deprivation there is an increase in the search for food due to a greater need for energy. The data analysis indicated that the IF animals showed a significant increase in the number of entries to the light area (Figure 2A) compared to the control rats (4.8 ± 0.8 versus 1.9 ± 0.6, p <0.05) and the administration of the bacteria reduced the number of entries, reaching similar values to the control group (2.6 ± 1.3). The IF group showed a slight but not significant reduction in the time to move from the dark to the light area (latency) compared to the control rats (184 ± 43 s versus 316 ± 48 s) (Figure 2B). Daily administration of B. uniformis CECT 7771 tended to increase the latency time, reaching values similar to those of the control group (289 ± 73 s). The time in the light area (Figure 2C) also tended to increase in the IF rats with respect to the control (99.4 ± 22.3 versus 65.7 ± 24.5, respectively) but the group that received B. uniformis CECT 7771 tended to show similar values to the control (60.7 ± 24.7 s). To assess anxiety-like behavior during the light phase, we performed the anxiety versus hunger test using a white openfield (Figure 2 D, E). This test is based on the conflict between neophobia / anxiety and hunger. All rats were fasted for 18 h; therefore, the effect of fasting influenced all groups equally. Rats significantly increased the latency time to initiate contact with food compared to controls (218 ± 26 s versus 118 ± 30 s, p <0.050) (Figure 2D), which suggests an increase in anxiogenic behavior. The administration of B. uniformis CECT 7771 reduced the latency time (117 ± 27 s, p <0.050), which indicates a reduction in anxiety. Regarding the latency to initiate contact with food and eat (Figure 2E), IF rats and IF + B rats needed more time to start eating (237 ± 25 s and 236 ± 28 s, respectively) than control rats (177 ± 32 s), although this increase was not significant.

Example 3. Effects of B. uniformis CECT 7771 on the expression of neuropetides and dopamine receptors in an eating disorder model.

3.1. Analysis of the expression of dopamine D1 and D2 receptors in the intestine and brain. The rats were anesthetized with sodium pentobarbital and a transcardiac perfusion was performed with 0.9% saline, followed by 4% paraformaldehyde in 0.1 mol / L phosphate buffer (pH 7.4). The brains were removed and subsequently fixed in the same fixative solution for 24 hours at 4 ^° C. The samples were then placed into histology cassettes and processed for permanent paraffin embedding on a Leica ASP 300 tissue processor ( Leica Microsystems, Nussloch, Germany). Paraffin-mounted sections 5 microns thick (5 pm) were cut and mounted on a coated slide glass. Tissue sections were then processed with the Envision Flex + kit (DAKO, Santa Clara, CA, USA) blocking endogenous peroxidase activity for 5 minutes and then incubated with the primary antibody. The reaction was visualized by Envision Flex + horseradish + peroxidase for 20 minutes and finally diaminobenzidine for 10 minutes. The sections were contrasted with Mayer's hematoxylin (DAKO S3309; Ready to use) for 5 minutes. The primary antibodies used were the following: Anti-dopamine D1 receptor antibody (Abcam, ab40653, 1: 500 for 40 minutes) and anti-dopamine D2-C-terminal receptor antibody (Abcam, ab191041, 1: 500 for 40 minutes ). Quantification was performed using Image (National Institutes of Health, Bethesda, MD, USA) (1.48v). For the analysis of dopamine D1 and D2 receptors, the areas of interest were selected. Cells positive for D1 and D2 were counted manually using ImageJ. For each rat, at least 10 fields (40 x) were quantified and the results were expressed as a percentage of control rats.

3.2. Expression of orexygenic and anorexygenic neuropeptides in the hypothalamus

To measure the expression of neuropeptides, RNA was isolated from the tissue, the hypothalamus (brain area) and a polymerase chain reaction or quantitative real-time PCR (RT-qPCR) was performed. For this the hypothalamus was removed and frozen immediately in liquid nitrogen. RNA was extracted from the tissue using the TRIsure reagent (Bioline, London, UK) and a homogenization process using a UP400S ultrasonic processor (Hielscher, Teltow, Germany). RNA quality was evaluated by measuring the absorbance ratio (A) A260 / A280 on a NanoDrop ND-1000 spectrophotometer (Thermo Scientific, Wilmington, USA). RNA (2 pg) was reverse transcribed (Applied Biosystems, Foster City, USA). A 20 ng amount of the resulting complementary DNA (cDNA) was used as a template for real-time PCR amplifications. Messenger RNA (mRNA) levels for specific genes were determined on a LightCycler480 instrument (Roche, Branchburg, USA). For each PCR reaction, a cDNA template was added to LightCycler 480 SYBR Green I Master (Roche, Branchburg, USA) containing the primer pairs for the corresponding gene. B2-microglobulin (b2M) was used as a housekeeping gene. The sequence and information for the primers are shown in Supplementary Table 1. All amplification reactions were performed in triplicate and mean threshold cycle numbers (Ct) of the triplicates were used to calculate relative mRNA expression of candidate genes. The magnitude of the mRNA expression change for the candidate genes was calculated using the standard 2-hAACt method. All data were normalized to housekeeping gene content and expressed as a percentage of control.

Supplementary Table 1. F: Forward primer, R: Reverse primer.

3.3. Effects on the expression of neuropetides and dopamine receptors B. uniformis CECT 7771 increases the expression of D1 positive cells in PFCx but not D2. We analyze the possible effects of B. uniformis CECT 7771 on dopamine receptors D1 R in the prefrontal cortex in the brain (PFCx) (Figure 3A) and D2R in the small intestine (Figure 3B). Cells expressing the D1 R and D2R receptors were analyzed by immunohistochemistry. IF rats tend to show a decrease in the number of cells expressing D1 R compared to the control (263 ± 12 versus 343 ± 25) in the PFCx, although the differences were not significant. B. uniformis CECT 7771 normalized the expression of D1 R in PFCx (398 ± 37, p <0.050). IF rats showed a significant decrease in D2 positive cells compared to control rats (185 ± 13 versus 390 ± 29, p <0.0010). The administration of B. uniformis CECT 7771 did not restore this alteration (237 ± 16, p <0.010). These results suggest that B. uniformis CECT 7771 decreases D1 and D2 positive cells in the small intestine.

Analysis of DA receptors in the mucosa of the small intestine showed that IF rats had a higher number of cells expressing D1 R compared to controls (376 ± 29 versus 219 ± 12, p <0.0010) as shown in the Figure 3C. Daily administration of B. uniformis CECT 7771 partially restored this alteration by reducing the expression of this receptor (304 ± 23, p <0.010). Immunohistochemical analysis of D2 positive cells (Figure 3D) also showed a significant increase in D2R expression in IF rats compared to control (497 ± 41 versus 232 ± 21, p <0.0010). B. uniformis CECT 7771 completely restored this alteration (241 ± 31, p <0.0010) in the addictive eating model. These results indicate that B. uniformis CECT 7771 could modulate the dopaminergic system in the enteric nervous system.

To elucidate whether the effect of B. uniformis CECT 7771 on binge eating and behavior was mediated by changes in appetite / satiety signals, we studied the expression of neuropeptide mRNA in the hypothalamus (Figure 4 A, B, C, D). . Orexigenic NPY expression levels (Figure 4A) increased significantly in IF rats with respect to controls (1 .55 ± 0.14 versus 1 .00 ± 0.11, p <0.050). Similarly, the expression levels of the anorectic AgRP (Figure 5C) were elevated in the hypothalamus of IF rats compared to controls (1.84 ± 0.20 versus 1.00 ± 0.14, p <0.010). The administration of B. uniformis CECT 7771 did not reduce these alterations (1.58 ± 0.16, p <0.050 for NPY and 1.97 ± 0.23, p <0.010 for AgRP). Analysis of mRNA expression of the anorectic neuropeptides CART (Figure 4B) and POMC (Figure 4D) did not reveal differences between IF and control rats (p <0.050); no administration of the bacteria had any effect (Figure 4 B, D). These results suggest that the increase in binge eating observed in the animal model of food addiction could be explained, at least in part, by the enhancement of the hypothalamic neuropeptides NPY and AgRP. However, these neuropeptides are not involved in the mechanism by which B. uniformis CECT 7771 reduced caloric intake during binge eating.

Example 4. Influence of B. uniformis CECT 7771 on the composition of the microbiota in a model of eating disorder.

4.1. Microbiota analysis by 16S rRNA gene sequencing DNA isolation from intestinal contents was performed using the MoBio PowerSoil ™ kit following the manufacturer's instructions. Previously cell lysis by incubation with lysozyme and mutanolysin favored at 37 C for 1 h ^and subsequently by mechanical cell disruption in a Mini-Bead Beater (BioSpec Products, Bartlesville, US) with two cycles of stirring for 1 minute. Genomic DNA was quantified by UV absorbance measurement (Nanodrop, Thermo Scientific, Wilmington, USA). The hypervariable regions V3-V4 of the gene 16S rRNA, were amplified in triplicate by PCR using 20 ng of DNA (1 pL) and 25 PCR cycles at 95 ^e C for 20 s, 40 ^e C for 30 s 72 ^e C during 20 s. The samples were barcoded to allow multiplexing during the sequencing process. Phusion high fidelity Taq Polymerase (Thermo Scientific) and the barcode primers SD-Bact-0341-bS-17 (CCTACGGNGGCWGCAG) (SEQ ID NO: 9) and SD-Bact-0785-aA were used during PCR. -21 (GACTACFIVGGTATCTAATCC) (SEQ ID NO: 10). The PCR products (-500 bp) were purified with the GFX PCR DNA and Gel Band Purification Kit Illustrator (GE Flealthcare, United Kingdom) and quantified using the Qubit 3.0 method and the Qubit dsDNA HS Assay Kit (Thermo Fisher Scientific, Waltham, MA, USA). Samples were multiplexed into a single sequencing by combining equimolar amounts of amplified DNA (-50 ng per sample) and sequenced in one lane. of the Illumina MiSeq platform with a 2x300 PE configuration (CNAG, Barcelona, Spain).

4.2. Bioinformatic and statistical analysis The sequences were filtered according to their quality using Flash software and separated according to their barcodes with the MOTHUR tool v1.39.5. After removal of the barcodes / primers, the chimeras were removed with the UCHIME algorithm and the 16S SILVA sequence reference database. The Operational Taxonomic Units (OTUs) or potential species were identified with the UCLUST algorithm implemented in USEARCH v8.0.1623. The OTUs were aligned using PyNAST and FastTree to estimate diversity based on phylogenetic distance. Analysis of alpha and beta diversity was performed using QIIME v1.9.1. Non-parametric methods were applied for statistical analyzes, such as the Kruskal-Wallis and Wilcoxon tests, applying the Benjamini-Hochberg correction in the case of multiple comparisons. A linear discriminant analysis (LDA) was performed to compare the abundance of taxonomic units (OTUs) between the different experimental groups and significant differences were established when the OTUs showed an LDA value of ³ 3.0. The PERMANOVA analysis was performed to evaluate the changes in the structure of the microbiota using the Bray-Curtís distance data. The Principal Coordinate Analysis (PCoA) allowed to visualize the changes in the composition of the microbiota between the groups. The analyzes were carried out in R v3.6.

4.3. Effects on the composition of the intestinal microbiota The main effects of the fasting protocol (IF) and the administration of B. uniformis (IF + B) were observed in the prevalence and abundance of various OTUs (Figure 5).

The administration of B. uniformis allowed to increase the abundance of Muribaculum spp. significantly reduced in the IF group compared to the control (LDA score = 4.44, p = 0.013). These species are indigenous components of the microbiota of mice. In addition, the administration of B. uniformis increased the abundance and prevalence of the following species: Akkermanisa muciniphila (LDA = 3.89, p = 0.044), Christensenella minuta (LDA = 3.11, p <0.001) and Faecalimonas umblicata (LDA = 3.65, p = 0.003). The species B. uniformis was also more abundant in the IF + B group than in the IF and in the control. In summary, the results show that B. uniformis is capable of restoring partially some of the microbiota alterations induced by the fasting protocol and increase some species with potentially positive effects against obesity and food intake (for example, Akkermanisa muciniphila and Christensenella minuta).

Claims

1. A strain of the genus Bacteroides, or a strain derived from it, for use in the prevention, risk reduction and / or treatment of sub-clinical or clinical conditions of eating disorders.

2. Strain of the genus Bacteroides for use, where the strain is B. uniformis CECT 7771.

3. Strain according to claim 1 or 2, wherein the eating disorders are selected from the list comprising: overeating, hyperphagia, binge eating disorder, addictive or selective food intake, bulimia nervosa, anorexia nervous system, anxiety associated with eating disorders and megarexia.

A strain according to any one of claims 1 to 3, wherein said strain is in the form of viable cells or in the form of non-viable cells.

5. Composition comprising a strain of the genus Bacteroides, or strain derived from it, for use in the prevention, risk reduction and / or treatment of sub-clinical or clinical conditions of eating disorders.

6. Composition for use according to claim 5 where the strain is B. uniformis CECT 7771.

7. Composition for use according to claim 5 or 6, where the eating behavior disorders or alterations are selected from the list that includes: excessive eating, hyperphagia, binge eating disorder, addictive or selective food intake, eater syndrome selective, bulimia nervosa, anorexia nervosa, anxiety associated with eating disorders and megarexia.

Composition for use according to any one of claims 5 to 7, wherein the strain is in the form of viable cells or in the form of non-viable cells.

Composition for use according to any one of claims 5 to 8 which additionally comprises at least one bioactive component.

Composition for use according to any of claims 6 to 9, which additionally comprises at least one microorganism other than strain CECT 7771 or strain derived or mutant thereof.

11. Composition for use according to claim 10, wherein the different microorganism is another strain of the genus Bacteroides, a lactic bacteria or a yeast strain.

12. Composition for use according to any one of claims 5 to 11 wherein the composition is a pharmaceutical or nutritional composition.

13. Composition for use according to claim 12, wherein the composition is pharmaceutical and comprises at least one pharmaceutically acceptable carrier and / or excipient.

Composition for use according to claim 13, wherein said composition is presented in a form adapted for oral, sublingual, nasal, bronchial, lymphatic, rectal, transdermal, inhaled or parenteral administration.

15. Composition for use according to claim 12, wherein the composition is nutritional and is selected from the list comprising a food, a supplement, a nutraceutical, a probiotic and a symbiotic.

16. Composition for use according to claim 15, wherein the composition is a food selected from the list that comprises: dairy product, a vegetable product, a meat product, a snack, chocolate, drink or baby food.

Composition for use according to any one of claims 5 to 16 wherein the composition has a strain concentration of between 10 ⁴ and 10 ¹⁴ colony forming units (ufe) per gram or milliliter of final composition.