Physiologically acceptable microbiological compositions comprising lactic acid bacteria and kluyveromyces marxianus yeast and uses thereof

Abstract

A physiologically acceptable composition comprising (i) at least one bacterium or a component, lysate or extract thereof, wherein the bacterium is selected from the group of Lactiplantibacillus, Lactobacillus and Bifidobacterium, and further comprising (ii) at least one component selected from the group consisting of K. marxianus yeasts, K. marxianus lysates, K. marxianus cell wall components and K. marxianus extracts. The invention further relates to the composition for use as a medicament. Furthermore, the invention relates to a cosmetic use of the composition.

Description

[0001] P133069PC00 Title: Physiologically acceptable microbiological compositions and uses thereof. The invention relates to a physiologically acceptable composition, comprising bacteria and yeast. The invention further relates to a method for preparing the composition. The invention further relates to the composition for use as a medicament, as a food additive or functional ingredient for nutraceuticals, food for special medical purposes, cosmeceuticals and functional foods, and as a feed additive of functional ingredient in animal nutrition. In particular, a composition according to the invention is suitable for use in the treatment of a medical disorder wherein weight loss is promoted or wherein fat deposition or fat accumulation is reduced. In a preferred embodiment, the composition is used in the treatment of obesity, overweight, type 2 diabetes, insulin resistance, metabolic syndrome, hypercholesterolemia, hyperlipidaemia, cardiovascular disease, lipodystrophy, lipohypertrophy or hypertension; the composition may also be used as adjuvant to bariatric surgery. A treatment of a medical disorder in accordance with the invention can be a preventive treatment or the treatment of an individual having said disorder. Furthermore, the invention relates to a cosmetic use of the composition for promoting weight loss, for reducing fat deposition or fat accumulation, or for managing weight in an individual. Probiotics are live microorganisms, which confer a health benefit to the host, when administered in adequate amounts. Already for centuries, long before becoming aware of their potential health benefits, humans have benefitted from microorganisms in food, for example in fermented milk and yoghurt. Modern probiotics-containing nutrients and pharmaceuticals are direct derivatives of the early fermented food. To date, the most common probiotics are from the bacterial genera Lactobacillus and Bifidobacterium, however also yeasts are increasingly being considered as effective probiotic organisms. Yeast-based probiotics are being recommended by several international guidelines to treat acute gastrointestinal disorders such as diarrhoea or chronical conditions such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). The probiotic activities of these yeasts are considered multifactorial and include improvement of gut barrier function, pathogen competitive exclusion, production of antimicrobial peptides, immune modulation, modulation of the microbiota, modulating energy metabolism and trophic effects. Yeast-based probiotics have many advantages over bacterial probiotics, such as a better withstanding of the extreme environments of the stomach to reach the intestines and an insensitivity to antibiotics providing the possibility to have probiotic effects during antibiotic treatment. Several yeast species have been shown to have a probiotic effect. Several yeasts have been suggested to act as probiotics such as some strains belonging to the genera Chrysonilia, Debaromyces, Hanseniaspora, Kluyveromyces, Lachanencea, Metschnikowia, Pichia, Saccharomyces, Torulaspora and Yarrowia (Ogunremi et al., 2015. J appl microbiol 117: 797-808; Sugiharto et al., 2018. J adv vet 5(3):332-342;Agarbati et al., 2020. Foods 9(3):287; Dufossé et al., 2021. J Fungi 7(3): 177). Lipids are essential for life. They are integral components of membranes, act as secondary messengers and signal transducers, and have crucial functions in energy storage. Dysregulation of lipid metabolism leads to diseases like obesity and type II diabetes, which are pressing public health concerns. Obesity is a significant public health concern affecting more than half a billion people worldwide. Moreover, obesity is detrimental to the quality of life as a whole and implies high health costs as a consequence of its associated morbidities. Obesity is an important risk factor for diseases including hypertension, type 2 diabetes, cardiovascular diseases, liver diseases and some cancers. It results from a long-term imbalance between energy intake and expenditure; however, the mechanisms underlying obesity seem to go beyond the long-held belief in caloric intake and lifestyle factors. It is becoming evident that host genetics, environment, diet and lifestyle, and systemic and adipose tissue inflammation play important roles in the development of this pathology. In recent years, microbial changes in the human gut were proposed as a possible cause of obesity and obesity-related disorders. In line with this, in several studies bacterial probiotics have been shown to have anti-obesity effects. For example inoculation of the gut microbiota of obese mice into axenic mice induces significant mass gain when compared with that of the gut microbiota of lean animals, paving the way to use selected bacteria (i.e. probiotics) for anti-obesity treatment (Turnbaugh et al., 2006. Nature 444: 1027-1031). Several probiotic strains of the genera Bifidobacterium and Lactobacillus have anti-obesity effects on different mouse models of induced obesity. Recently, a study in Caenorhabditis elegans, a model organism used to study human metabolic disorders, pointed towards a bacterial strain, more specifically Bifidobacterium animalis subsp. lactis CECT 8145, as a promising probiotic for obesity disorders (Martorell et al., 2016. J Agric Food Chem 64: 3462−3472). There is a continuing need to provide alternative treatment possibilities of medical disorders, in particular metabolic disorders related to a dysregulation of the lipid metabolism, such as obesity, overweight, type 2 diabetes, insulin resistance, metabolic syndrome, hypercholesterolemia, lipodystrophy, lipohypertrophy or hypertension. There is further a continuing need to provide alternative products suitable for promotion of weight loss or reduction of fat deposition or fat accumulation. It is in particular an object to provide a composition, which is suitable to provide an improved effect in terms of weight loss or reduction or in terms of reduction in fat deposition or fat accumulation compared to known probiotics as described in the above discussed prior art. One or more further objects that may be addressed will follow from the description herein below. We have now found that one or more of said objects are realized by providing a specific composition comprising at least one bacterium and at least one yeast. Accordingly, the invention relates to a physiologically acceptable composition comprising (i) at least one bacterium or a component, lysate or extract thereof, wherein the bacterium is a lactic acid producing bacterium selected from the group of Lactiplantibacillus, Lactobacillus and Bifidobacterium, and further comprising (ii) at least one component selected from the group consisting of K. marxianus yeasts, K. marxianus lysates, K. marxianus cell wall components and K. marxianus extracts. Preferably, said at least one bacterium comprises or is a Lactiplantibacillus or a component, lysate or extract thereof, more preferably a Lactiplantibacillus plantarum (L. plantarum) or a component, lysate or extract thereof. Preferably, said physiologically acceptable composition further comprises at least one component selected from the group consisting of S. boulardii yeasts, S. boulardii lysates, S. boulardii cell wall components, and S. boulardii extracts. As illustrated in the examples, particularly good results have been achieved with a physiologically acceptable composition, comprising L. plantarum, inactivated K. marxianus yeast and inactivated S. boulardii yeast. Further, the invention relates to said physiologically acceptable composition for use in the treatment of an individual by therapy. Preferably, in said treatment, weight loss is promoted or fat deposition or fat accumulation is reduced, and / or the individual is overweight (typically a Body Mass Index (BMI) of 25 kg / m2or higher for an adult human) or obese (typically a BMI of 30 kg / m2or higher or a BMI of 35 kg / m2or higher for an adult human). Further, the invention relates to a use of a physiologically acceptable composition as a food additive, a feed additive, a functional food in human nutrition, a functional food in animal nutrition, a food additive or functional ingredient for nutraceuticals. Further, the invention relates to the physiologically acceptable composition according to the invention for use in the treatment of (an individual with) obesity, overweight, type 2 diabetes, insulin resistance, metabolic syndrome, hypercholesterolemia, hyperlipidaemia, cardiovascular disease, lipodystrophy, lipohypertrophy or hypertension. Further, the invention relates to a use of the physiologically acceptable composition as a probiotic, a postbiotic, a paraprobiotic, a prebiotic, a symbiotic or a probiotic-substitute. Further, the invention relates to a cosmetic use of said physiologically acceptable composition for promoting weight loss in an individual, for reducing fat deposition or fat accumulation or as a weight management supplement. Further, the invention relates to a food product, comprising a composition according to the invention, preferably a weight management food product. In a use in accordance with the invention (non-medical or medical), said lactic acid producing bacterium, K. marxianus and optionally present S. boulardii (or components thereof) are typically active ingredients of the composition. A medical use according to the invention can be a preventive treatment (prophylactic) or a treatment of an individual, in particular a human, having a medical disorder to be treated. A treatment of an individual having a medical disorder can comprise curing the medical disorder, reducing suffering, alleviating or relieving one or more symptoms associated with said medical disorder. The effectivity of a prophylactic treatment can routinely be determined, e.g. by comparing cohorts or test animals treated with a composition for use according to the invention and a reference product (placebo), with a reduced incidence. The effect of a treatment of an individual having the disorder can be a complete cure, an alleviation of a symptom, reduced suffering etc., which can also be routinely determined on the basis of the information disclosed herein and common general knowledge. As illustrated in the Examples below, a composition according to the invention has been found effective in the reduction of fat deposition, using Caenorhabditis elegans as an in vivo model. Many genes involved in the fat regulatory pathways are highly conserved between C. elegans and mammals, including humans (Ashrafi et al., 2003. Nature 421: 268-272). C. elegans stores fat in the form of lipid droplets in their intestinal and hypodermal cells. These droplets can easily be visualised and quantified after staining with fluorescent dyes, making C. elegans an ideal model to evaluate the effects of different compositions on the accumulation of body fat. Furthermore, the results of C. elegans studies have been successfully validated in clinical studies in humans. For example, the findings of Martorell et al. (Martorell et al., 2016. J Agric Food Chem 64: 3462−3472), namely that a specific Bifidobacterium animalis subsp. lactis CECT 8145 was able to reduce body fat in C. elegans, have been confirmed in a clinical study in obese humans, where treatment with said Bifidobacterium resulted in a significant reduction in obesity-related measurements such as waist circumference and BMI (Padret et al., 2019. Int J Obes 43: 1863-1868). These results prove that C. elegans is a good model organism to study the mechanisms underlying biology of fat regulatory pathways and make a successful translation from C. elegans to humans plausible. It was found that a composition according to the invention, comprising at least one of said bacteria and K. marxianus, caused a significant reduction in fat deposition in the C. elegans model. In particular, it was found that a composition comprising a Lactiplantibacillus plantarum bacterium and a K. marxianus yeast, lead to a significant reduction of the fat deposition in C. elegans. Further components, such a S. boulardii yeast, prebiotic fiber or a medium chain triglyceride (MCT) oil, can advantageously be present in the composition. This observed effect, i.e. the reduction of fat deposition in C. elegans, is indicative of a positive effect for use in the treatment or prevention of metabolic disorders characterized by a dysregulated lipid metabolism such as obesity or overweight and associated disorders such as type 2 diabetes, insulin resistance, metabolic syndrome, hypercholesterolemia, hyperlipidaemia, cardiovascular disease, lipodystrophy, lipohypertrophy and hypertension. Furthermore, the observed effect makes a composition according to the invention particularly effective for promoting weight loss in an individual, for reducing fat deposition or fat accumulation of an individual, or for managing weight of an individual. In particular, a surprising effect is obtained by combining a L. plantarum bacterium, and an inactivated K. marxianus yeast, further comprising an inactivated S. boulardii. In the examples, it is illustrated how such composition resulted in a reduction in fat deposition without affecting the development of the C. elegans, whilst individual bacteria or combinations with viable yeasts did not result in the same effects. The most advantageous effect in terms of both a reduction in fat deposition and development of the C. elegans was observed for a composition comprising L. plantarum bacterium, an inactivated K. marxianus yeast and an inactivated S. boulardii. The physiological composition according to the invention can contain viable yeast cells selected from the group of K. marxianus and / or S. boulardii. However, as illustrated by the Examples, viable yeasts do not need to be present. Accordingly, the inventors further conclude that one or each of said K. marxianus and S. boulardii as comprised in a composition according to the invention can also be replaced fully or in part by a yeast lysate, cell wall material or a yeast extract of respectively K. marxianus and S. boulardii. Fig. 1 depicts the in vivo inhibition of fat deposition by different compositions in a C. elegans model. Oil Red O (ORO) staining was used to assess the fat storage in C. elegans day-4 adult worms. The y-axis shows the average analogue-to-digital units (ADUs) across worms. The standard feed E. coli OP50 was taken along as a positive control (left bar). For the different tested compositions, results of one-way ANOVAtests compared with ABB S20 are shown (NS non-significant, ***p<0.001). Results for ABB S20 were compared to OP50. Fig. 2. shows the association of fat deposition inhibition with development time in a C. elegans model. On the x-axis the average ADUs across worms, indicative for the increasing fat deposition is shown. On the y axis the days until G2 appear, indicative for delay in development, is shown. For the purpose of clarity and a concise description, features are described herein as part of the same or separate embodiments, however, it will be appreciated that the scope of the invention may include embodiments having combinations of all or some of the features described. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well. The term " or" includes any and all combinations of one or more of the associated listed items, unless the context clearly indicates otherwise (e.g. if an “either ….or” construction is used). It will be understood that the terms "comprises" and "comprising" specify the presence of stated features but do not preclude the presence or addition of one or more other features. It will be further understood that when a particular step of a method is referred to as subsequent to another step, it can directly follow said other step or one or more intermediate steps may be carried out before carrying out the particular step, unless specified otherwise. In the context of this application, the term "about" means generally a deviation of 15 % or less from the given value, in particular a deviation of 10% or less, more in particular a deviation of 5% or less. As is used herein, the term “physiologically acceptable composition”, refers to a composition that is suitable for administration to an individual such as an animal or a human. As is used herein, the term “probiotics”, refers to live microorganisms, which when administered in adequate amounts, confer a health benefit to an individual. Probiotics include all sorts of microorganisms including bacteria and yeasts. As is used herein, the term “inactivated”, or “dead”, or “non-viable”, refers to an organism, such as a yeast or bacterium, not being capable of reproduction or colonization. An inactivated organism can have intact or broken cell membranes. The skilled person will be able to obtain an inactivated organism based on common general knowledge and the information disclosed herein. Possible means include irradiation, heat inactivation, sonication, lyophilization and chemical inactivation. As used herein, the term “heat-killed”, refers to an organism inactivated by heat-treatment and such not capable of metabolic activity nor colonization. Means of heat-treatment to inactivate an organism are known to a person skilled in the art and include tyndallization, pasteurization, ultra-high temperature (UHT) heating, Ohmic heating (or Joule heating), blanching, drying, boiling and sterilization. As is used herein, the term “tyndallization”, refers to a sterilization process often used to heat-kill probiotic microorganisms. Tyndallization involves repeating a heat-killing step for a certain consecutive days, for example as described on page 11 in the Handbook of Microbiological Media (third edition, 2004, CRC Press) by Ronald M. Atlas. Therefore, the term “tyndallized”, refers to an organism having been heat-killed by tyndallization and such not capable of metabolic activity or colonization. As used herein, the term “cell lysis” refers to any type of cell disruption that results in the release of intercellular biological components naturally contained in the cells of an organism. Therefore, the term “lysate”, refers to a product obtained after cell lysis. A “lysate”, as used herein, means in particular essentially the entire lysate obtained by lysis of an organism and therefore comprises macromolecules such as DNA, RNA, proteins, peptides and lipids from the lysed cell; as well as cellular debris, including cell wall material, and cell membrane components from the lysed cells. Methods for obtaining a lysate are known to a person skilled in the art and include enzymatic, physical and chemical methods. Cell wall components can be separated from the fluid part of the lysate e.g. by centrifugation of filtering. As used herein, the term “extract” of a microorganism, refers to a fluid part or fraction of the microorganism cell or lysate, in particular liquid contents of yeast or bacterial cells, in particular obtainable by filtration or by centrifugation, or a fraction thereof, obtainable by extraction from the cells or the lysate, using an extracting phase, As used herein, the term “metabolite”, refers to any substance derived from the growth or maintenance of the microorganism, persisting in the culture medium and with no need to be preserved by special techniques. Examples of metabolites are organic and inorganic acids, proteins, (poly)peptides, amino acids, (co)enzymes, fatty acids, (esterified) lipids, carbohydrates (including monosaccharides, disaccharides and polysaccharides), lipoproteins, glycolipids, glycoproteins, sugar phosphates, vitamins, salts, metals, or nucleic acids. As is used herein, the term “alive”, or “viable”, refers to an organism being capable of reproduction or colonization. As is used herein, the term “individual”, refers to any living organism such as an animal or human that can benefit from the administration of a physiologically accepted composition of the invention. The term “animal” as used herein, refers in particular to vertebrate animals including fish, birds, mammals, reptiles and amphibians. The animal can be a farm animal, domestic animal or laboratory animal. An individual, which may be treated in accordance with the invention may in particular be selected from humans, nonhuman primates and monkey species, cows, sheep, pigs, goats, horses, dogs, cats, rodents such as mice, rats and guinea pigs, poultry, such as chickens, hens, turkeys, ducks and geese and aquatic animals such as fish and shrimp. The term individual does not denote a particular age or sex (such as male / female). Thus, humans of any age group, including adults (older than 18 years of age) and children (0-18 years of age), e.g. newborn individuals (0- 12 months of age), toddlers (12-36 months of age), can be treated in accordance with the invention. In a preferred embodiment, the composition is for use of the treatment of a human, for which the examples in particular illustrate a beneficial, even synergistic, effect on intestinal cells. In another preferred embodiment, the composition is for use in the treatment of a non-human mammal. As is used herein, the term “nutritional product”, refers to a composition intended for ingestion by an individual providing at least one nutrient to the individual. Nutritional products generally comprise one or more components selected from the group consisting of protein, fat, carbohydrate and micro- nutrients. As is used herein, the term “nutraceutical”, refers to any nutritional product providing an extra health benefit in addition to the basic nutritional value found in foods. As is used herein, the term “cosmeceutical”, refers to any cosmetic product with bioactive ingredients purported to have a health benefit. As used herein, the term “prebiotic” refers to any substance that is selectively utilized by microorganisms conferring a health benefit to an individual. Prebiotics are in particular nondigestible food ingredients that stimulate the growth and / or activity of said microorganisms. As used herein, the term “postbiotic” refers to any preparation of inactivated microorganisms and / or their components that confers a health benefit to an individual. The components that confer a health benefit may be a mixture of metabolic products secreted by probiotics in cell-free supernatants, such as enzymes, secreted proteins, short chain fatty acids, vitamins, secreted biosurfactants, amino acids, peptides, organic acids, etc. As used herein, the term “paraprobiotic” refers to inactivated microorganisms and / or cell fractions that confers a health benefit to an individual. As used herein, the term “synbiotic” or “symbiotic”, refers to any preparation comprising a mixture of probiotics and prebiotics. As used herein, the terms “overweight” and “obesity” refer in particular to abnormal or excessive fat accumulation that may impair health. For humans, the WHO definitions as available on 9 June 2021 can be used to determine whether a human is overweight or obese (https: / / www.who.int / news-room / fact- sheets / detail / obesity-and-overweight). For human adults, the WHO definition is based on BMI. The term “body mass index (BMI)”, refers to a measure of an individual’s weight compared according to height, which is a proxy for the relative percentage of fat and muscle mass of the human body. BMI is defined as an individual’s weight (kg) divided by the square of the individual’s height (m2), and can be used to define whether an individual is overweight. Typically, an adult human is considered underweight if the individual’s BMI is less than 18.5 (kg / m2); normal if the adult human’s BMI is equal to or greater than 18.5 (kg / m2) and less than 25.0 (kg / m2), overweight if the adult human’s BMI is equal to or greater than 25.0 (kg / m2) and less than 30.0 (kg / m2), obese if the adult human’s BMI is equal to or greater than 30.0 (kg / m2) and severely obese if the individual’s BMI is equal to or greater than 40.0 (kg / m2). For humans under 5 years of age, overweight is weight-for-height greater than 2 standard deviations above WHO Child Growth Standards median; and obesity is weight-for-height greater than 3 standard deviations above the WHO Child Growth Standards median (see also https: / / www.who.int / tools / child-growth- standards / standards). For humans aged between 5-19 years, overweight is BMI- for-age greater than 1 standard deviation above the WHO Growth Reference median; and obesity is greater than 2 standard deviations above the WHO Growth Reference median (see also https: / / www.who.int / tools / growth-reference-data-for- 5to19-years / indicators / height-for-age). Regarding non-human individuals, the skilled person will be able to determine whether an animal is overweight or obese based on common general knowledge, for instance making use of a body condition score (BCS) for a specific mammal, e.g. a cat, a dog or a horse. As used herein, the term “cosmetic use”, refers to a non-therapeutic use. A cosmetic use (cosmetic promotion of weight loss, cosmetic reduction of fat depositions / accumulation, cosmetic weight management) is not directed at improving or maintaining health, but performed for an aesthetic reason (such as visual appearance, body shape). Medical and cosmetic uses in accordance with the invention are not inextricably linked; e.g. individuals having a healthy weight and fat levels may use the composition according to the invention in order to change their weight or body shape for aesthetic reasons without experiencing any health benefit. A cosmetic use can comprise oral ingestion of a composition according to the invention with the aim of promoting non-medical weight loss in an individual, for non-medically reducing fat deposition or for non-medical fat accumulation in an individual, or for non-medically managing weight in an individual. Individuals with A composition according to the invention may typically be used cosmetically by individuals having a neither overweight nor underweight (a normal weight), by individuals without markers that are characteristic for a dysregulated lipid metabolism or both. In a cosmetic use surgical treatment, therapeutic treatment and diagnostic treatment of the human or animal body are excluded. As used herein, the term “lactic acid producing bacterium”, refers to a general term for a bacterium that can produce lactic acid, at least when living. The term refers not only to lactic acid-producing bacteria belonging to the orderLactobacillales, but includes other lactic acid producing bacteria such as forexample Bifidobacterium belonging to the order Bifidobacteriales. Hereinbelow, the term “ bacterial material” or “bacterial based fraction” is used as a genus for living bacterial cells, inactivated bacterial cells, bacterial lysates, bacterial cell wall components and bacterial extracts. The term “ yeast material” or “yeast based fraction” is used as a genus for living yeast cells, inactivated yeast cells, yeast lysates, yeast cell wall components and yeast extracts. Likewise, the term “microbiological material” is used as a genus for living microorganisms, inactivated microorganisms, lysates of microorganisms, cell wall components of microorganisms and extracts of microorganisms. Components of a physiologically acceptable composition In this invention, a physiological acceptable composition comprises a lactic acid producing bacterium selected from the group of the bacterial generaLactiplantibacillus, Lactobacillus and Bifidobacterium. Preferably, the bacteriumis a Lactiplantibacillus plantarum, which is a member of the genus Lactiplantibacillus. This species is also referred to in the art as Lactiplantibacillusplantarum, Lactobacillus plantarum, Lactobacterium plantarum, Streptobacteriumplantarum, Lactobacillus arabinosus and Lactobacillus arizonensis. In an embodiment, the composition comprises one or more strains selected from the group consisting of Lactiplantibacillus plantarum and Lactobacillus gasseri. Good results have in particular be achieved with a composition according to the invention comprising L. plantarum ABB S20cells. Accordingly, L. plantarum ABB S20 cells, an extract of L. plantarum ABB S20 cells, a lysate of L. plantarum ABB S20 cells or cell wall material of L. plantarum ABB S20 cells thereof is present in a preferred composition of the invention. L. plantarum ABB S20 has been deposited on 01 August 2023 with the National Measurement Institute (1 / 153 Bertie Street, Port Melbourne, Victoria, Australia 3207) under accession number V23 / 013536 on the same terms as laid down in the Budapest Treaty. The deposit was made by AB Mauri Technology & Development Pty. Ltd., 1 Richardson Place, North Ryde NSW, 2113, Australia (AB Mauri T&D). The depositor has authorised the applicant to refer to the deposited material in the application and has given his unreserved and irrevocable consent to the deposited material being made available to the public in accordance with Rule 31(1)(d) of the European Patent Convention (EPC). A statement of authorisation and consent is being filed with this application. In a further preferred embodiment, the L. plantarum is a derivative strain of L. plantarum ABB S20. A person skilled in the art will be able to determine if a given bacterial strain is classified or classifiable as genus Lactiplantibacillus, genus Lactobacillus, genus Bifidobacterium, species Lactiplantibacillus Plantarum and / or species Lactobacillus gasseri by using standard references such as e.g by using taxonomic classification based on the identification of one or more variable regions of the 16S ribosomal RNA gene (Vandamme et al., 1996. Microbiol Rev 60: 407-438) or full- length 16S ribosomal RNA gene-based taxonomic classification (Singer et al.n 2016. ISME J 10: 2020 - 2032) or by using Randomly amplified polymorphic DNA Polymerase Chain Reaction (RAPD PCR) (Johansson et al., 1995. Lett Appl Microbiol 21: 155-159). In this invention, the K. marxianus can be any strain belonging to the species K. marxianus. This species is also referred to in the art as Saccharomyces marxianus, Candida kefyr, Candida pseudotropicalis, Kluyveromyces fragilis, Kluyveromyces cicerisporus. In the physiologically acceptable composition inaccordance with the invention, the K. marxianus is typically inactivated. In anembodiment, the composition comprises one or more strains selected from the group consisting of K. marxianus AS41, K. marxianus B0399, K. marxianus CIDCA 8154, K. marxianus CBS1553, K. marxianus M3, K. marxianus V21 / 012435, K. marxianus Z17 and derivative strains of one or more of said strains. Good results have in particular be achieved with a composition according to the invention comprising K. marxianus V21 / 012435 cells. K. marxianus V21 / 012435 has been deposited on 24 June 2021 with the National Measurement Institute (1 / 153 Bertie Street, Port Melbourne, Victoria, Australia 3207) under accession number V21 / 012435 on the same terms as laid down in the Budapest Treaty. The deposit was made by AB Mauri Technology & Development Pty. Ltd., 1 Richardson Place, North Ryde NSW, 2113, Australia (AB Mauri T&D). The depositor has authorised the applicant to refer to the deposited material in the application and has given his unreserved and irrevocable consent to the deposited material being made available to the public in accordance with Rule 31(1)(d) of the European Patent Convention (EPC). A statement of authorisation and consent is being filed with this application. Live K. marxianus V21 / 012435 is available from ABBiotek HNH upon demand as ABB S7. Tyndallised K. marxianus V21 / 012435 is available from ABBiotek HNH as ABB S8. Accordingly, K. marxianus V21 / 012435 cells, an extract of K. marxianus V21 / 012435 cells, a lysate of K. marxianus V21 / 012435 cells or cell wall material of K. marxianus V21 / 012435 cells thereof is present in a preferred composition of the invention. In a further preferred embodiment, the cells are a derivative of K. marxianus V21 / 012435 or the extract, lysate or cell wall material is from a derivative strain of K. marxianus V21 / 012435. In this invention, the S. boulardii can be any strain classified or classifiable as S. cerevisiae var. boulardii, in particular any such strain that is probiotic in a living or inactivated form. In the physiologically acceptable composition in accordance with the invention, the S. boulardii is typically inactivated. In an embodiment, the composition comprises at least one S. boulardii selected from the group of a S. boulardii DSM 33954 a S. boulardii CNCM I-745, S. boulardii Hansen CBS 5926, S. boulardii BLD-3, S. boulardii CCTCC M2012116, S. boulardii CNCM I-1079, S. boulardii ATCC MYA-796, S. boulardii Unique28, S.boulardii Kirkman, S.boulardii Unisankyo, S. boulardii CNCM I-3799 and derivative strains of any one or more of said strains. In particular good results have been achieved with a composition comprising inactivated S. boulardii DSM 33954 (available as ABB S3 from ABBiotek HNH- UK, https: / / humannutrition.abbiotek.com / ). S. boulardii DSM 33954 has been deposited on 19 July 2021 with the Leibniz Institute DSMZ – German Collection of Microorganisms and Cell Cultures GmbH (Inhoffenstr. 7 B, D-38124 Braunschweig, Germany) under accession number DSM 33954 on the same terms as laid down in the Budapest Treaty. The deposit was originally made by MD’E Srl, Via tevere 16, 64020 Castelnuovo Vomano, Italy. All rights and duties in connection with this patent deposit were transferred to NTP BIOTECH Srl, Via F.P. Michetti 3, Penna Sant’Andrea, Italy, being the current depositor of the deposited culture. The depositor has authorised the applicant to refer to the deposited material in the application and has given his unreserved and irrevocable consent to the deposited material being made available to the public in accordance with Rule 31(1)(d) of the European Patent Convention (EPC). A statement of authorisation and consent is being filed with this application. A person skilled in the art will be able to determine if a given yeast strain is classified or classifiable as S. cerevisiae var. boulardii or as K. marxianus by using standard references such as e.g. “The yeasts, a taxonomic study” (CP Kurtzman, JW Fell and T Boekhout), 5thedition, 2011, Elsevier. Furthermore, person skilled in the art will be able to differentiate S. cerevisiae var. boulardii from other yeast strains belonging to the species S. cerevisiae based on standard references such as e.g. Edwards-Ingram L, Gitsham P, Burton P, et al., “Genotypic and physiological characterization of Saccharomyces boulardii, the probiotic strain of Saccharomyces cerevisiae”, Appl Environ Microbiol 2007; 73: 2458–67. As used herein, a “derivative strain” is a strain derived from a strain disclosed herein, including through hybridization, mutagenesis, recombinant DNA technology, mating, cell fusion, or cytoduction between strains. Further, derivative strains, in particular derivative strains of bacteria, may be obtained by transformation, transduction or conjugation. A derivative strain can be a strain found in nature (a natural strain), yet isolated from its natural environment. In an embodiment, the derivative strain is not found in nature (a non-natural strain). Advantageously, the derivative strain is a progeny strain of a parent strain (i.e. a strain from which it is a progeny), which progeny strain typically is the product of a mating between said parent strain and another parent strain or the progeny strain is a descendent of that mating product. In an embodiment, the derivative strain is a hybrid strain that is producible or has been produced by a method comprising using a strain (such as a L. plantarum, K. marxianus or S. boulardii strain mentioned in the present disclosure, or a derivative of any of these) as a parent strain for hybridisation. In a preferred embodiment, the progeny strain can be obtained using a hybridization method comprising hybridization of a parent strain (such as a L. plantarum, K. marxianus or S. boulardii strain mentioned in the present disclosure, or a derivative of any of these) and at least one step of screening or selection of the hybrid obtained, which selection is based on one or more defining characteristics of said parent strain. For instance, a defining characteristic can be based on taxonomic classification (e.g.16S characterization for L. Plantarum; 18S or ITS for K. Marxianus and SB. Preferably, a defining characteristic is a reduction of fat deposition for a combined administration of L. plantarum and K. marxianus and optionally further combined with S. boulardii. Tests for screening or selecting on the basis of said defining characeristics can be based on the Examples, herein below. In a particularly preferred embodiment, the derivative strain is obtained or obtainable by a method comprising, (a) providing: (i) a first strain (such as a L. plantarum, K. marxianus or S. boulardii strain mentioned in the present disclosure, or a derivative of any of these); and (ii) a second strain, wherein the second strain is in the same clade as the first strain; (b) inducing mating (e.g. sporulation or conjugation) of the first and the second strain; (c) screening or selecting for a derivative strain. In a particularly preferred embodiment, the derivative strain of a spore- forming strain is obtained or obtainable by a method comprising, (a) providing: (i) a first strain (such as a L. plantarum, K. marxianus or S. boulardii strain mentioned in the present disclosure, or a derivative of any of these); and (ii) one or more additional strains that are in the same clade as the first strain; (b) inducing sporulation of the first strain and the one or more additional strains to produce spores; (c)mixing the spores of step (b) to allow for hybridization of the spores; and (d) screening or selecting for the derivative strain. In a further preferred embodiment, the derivative strain is an evolved strain, in particular a strain obtained or obtainable be an evolution induced by applying selection pressure to the parent strain or a derivative thereof). In a further preferred embodiment, the derivative strain is a mutant strain of the parent strain or a derivative thereof. A mutant can be obtained by contacting the derivative with a mutagen. Examples of mutagens are ethyl methanesulfonate (EMS), ultraviolet light (UV), X-rays, methylmethane sulphonate (MMS), nitrous acid, nitrosoguanidine (NNG), acridine mustard, 2- methoxy-6-chloro-9[3- (ethyl-2-chloroethyl)aminopropylamino]acridine·2 (ICR-170), and nitrogen mustard. In a further preferred embodiment, strain is a genetically modified strain. In particular, the genetically modified strain has a modification made using gene editing (also called genome editing). The gene editing can in particular comprise a modification to suppress expression of a gene, enhance expression of a gene, introduce one or more genomic nucleic acids, delete one or more genomic nucleic acids, introduce a gene, or delete a gene. The relative amounts of the at least one bacterium or a component, lysate or extract thereof, wherein the bacterium is a lactic acid producing bacterium selected from the group of Lactiplantibacillus, Lactobacillus and Bifidobacterium, can vary within wide limits. Generally, the bacterium-based fraction of the composition according to the invention is: 0.05 – 99.95 wt.%, preferably 5-90 wt.%, more preferably 10-90 wt.%, more preferably 15-80 wt.%, in particular 20-80 wt.%, more in particular 20-60 wt.%, more in particular 25-50 wt.%, based on total microbiological components of the composition. The relative amounts of the at least one component selected from the group consisting of K. marxianus yeasts, K. marxianus lysates, K. marxianus cell wall components and K. marxianus extracts (also referred to herein as K. marxianus- based fraction) can vary within wide limits. Generally, the K. marxianus-based fraction of the composition according to the invention is: 0.05 – 99.95 wt.%, preferably 5-90 wt.%, more preferably 10-90 wt.%, more preferably 15-80 wt.%, in particular 20-80 wt.%, more in particular 20-60 wt.%, more in particular 25-50 wt.%, based on total microbiological components of the composition. The relative amounts of the at least one component selected from the group consisting of S. boulardii yeasts, S. boulardii lysates, S. boulardii cell wall components and S. boulardii extracts (also referred to herein as S. boulardii-based fraction) ) can vary within wide limits. Generally, the S. boulardii-based fraction of the composition according to the invention is: 0 – 90 wt.%, preferably 0.05 – 90 wt. %, more preferably 5-80 wt. %, in particular 10-60 wt.%, more in particular 15-50 wt.%, based on total microbiological components of the composition. Usually, the bacterium-based and yeast-based fraction form together at least 10 wt.% of the total microbiological material (such as bacterial, algae or fungal cells, lysates thereof, extracts thereof, cell wall parts thereof), preferably at least 25 wt. %, more preferably at least 50 wt. %, in particular at least 75 wt.%. If desired, other microbiological material may be present in the composition, in particular a probiotic micro-organism or cell material of a probiotic micro-organism. Thus, the total of the bacterium-based fraction and the yeast-based fraction is 100 % of the total microbiological material or less, for instance 99 wt. % or less, based on total microbiological material. In an advantageous embodiment, the physiological composition comprises (all based on based on total microbiological components and preferably on total microbiological material) 5-95 wt.% L. plantarum, 5-95 wt.% K. marxianus-based fraction (typically inactivated K. marxianus) and 0-80 wt. % S. boulardii-based fraction (typically inactivated S. boulardii). In particular, good results are achieved, e.g. with respect to fat deposition reduction with a composition having a L. plantarum-based fraction content in the range of 15-50 wt. %,a K. marxianus- based fraction content in the range of 15-50 wt. % and a S. boulardii-based fraction content in the range of 0-50 wt. %, all based on of the total microbiological material of the composition, with the proviso that the total of said three fractions is 100 wt. % or less. Herein, advantageously the yeast based fraction at least substantially consists of inactivated yeast cells. Herein, advantageously, the total microbiological material at least substantially consists of inactivated yeast cells. As the skilled person will understand, based on the information disclosed herein and common general knowledge, different contents may be applied with satisfactory results. Since safety issues with the use of live microorganisms have been arisen, for example in fragile or immunocompromised patient groups or neonates, interest in using non-viable inactivated probiotics has increased. Several inactivation methods are known to a person skilled in the art and include irradiation, heat inactivation, sonication, lyophilization and chemical inactivation. Tyndallization is a sterilization process often used to heat-kill probiotic microorganisms. Accordingly, typically the physiologically acceptable composition of the invention comprises non-viable K. marxianus and optionally non-viable S. boulardii. Preferably, the inactivated yeast is heat-killed. More preferably, the inactivated yeast is tyndallized. The tyndallization may be based on tyndallization processes generally known in the art. In particular, good results have been achieved with a composition comprising a tyndallized K. marxianus and further a tyndallized S. boulardii. Usually at least substantially all of the yeast cells present in the physiologically acceptable composition according to the invention are non-viable. Thus, usually the yeast material is essentially free of viable yeast cells. However, in a specific embodiment the physiologically acceptable composition of the invention comprises at least one live yeast selected from S. boulardii and K. marxianus. If at least one of said yeast is present in an alive form, preferably at least K. marxianus is present in an alive form. If present, the content of live yeast material is typically a minor fraction of total yeast material, in particular 10 wt.% or less, more in particular 1 wt. % or less. The physiologically acceptable composition of the invention preferably comprises living L. plantarum; in a particular preferred embodiment, 50-100 wt.% of the L. plantarum material (L. plantarum cells, L. plantarum lysate, L. plantarum components) is living L. plantarum The L. plantarum in the physiologically acceptable composition of the invention for administration into the gastrointestinal tract is usually present in a concentration ranging from 106cells per gram (based on total weight of the microbiological components) to 1011cells per gram (based on total weight of the microbiological components)¸ preferably from 108cells per gram (based on total weight of the microbiological components) to 5x1010cells per gram (based on total weight of the microbiological components). The K. marxianus in the physiologically acceptable composition of the invention for administration into the gastrointestinal tract is usually present in a concentration ranging from 106cells per gram (based on total weight of the microbiological components) to 1011cells per gram (based on total weight of the microbiological components)¸ preferably from 108cells per gram (based on total weight of the microbiological components) to 5x1010cells per gram (based on total weight of the microbiological components). The S. boulardii as optionally included in the physiologically acceptable composition of the invention for administration into the gastrointestinal tract is usually present in a concentration ranging from 106cells per gram (based on total weight of the microbiological components) to 5 x 1011cells per gram (based on total weight of the microbiological components)¸ preferably from 108cells per gram (based on total weight of the microbiological components) to 1011cells per gram (based on total weight of the microbiological components), more preferably 109cells per gram (based on total weight of the microbiological components) to 5x1010cells per gram(based on total weight of the microbiological components). Concentrations of live and inactivated bacteria and yeasts are measured and expressed in cells per gram total microbiological components. For live bacteria and yeasts the concentration in ‘cells per gram’ is equivalent as ‘colony forming units (CFU) per gram total microbiological components. If a combination of live cells and inactivated cells (not colony forming) are present’, the total of cells is will usually be in the above mentioned usual range, preferably in an above mentioned preferred range or more preferred range. For a lysate, for an extract or for cell wall components a suitable concentration usually corresponds to the amount of lysate, extract respectively cell wall components obtainable from 104cells per gram (based on total weight of the microbiological components) to 1011cells per gram (based on total weight of the microbiological components). A composition according to the invention may further comprise prebiotic fiber. A prebiotic fiber, also referred to as “dietary fiber”, means cell components of plants, which are hardly or low digestible by animals, such as cellulose, lignin, hemicellulose, pectin and low-digestible water-soluble polysaccharides which are not digested by amylases. A preferred dietary fiber is dextran, i.e. a water soluble α-glucan comprising at least 95% α-D-(1,6) glycosidic linkages. An example of a preferred prebiotic fiber is Dextran ABB I5 (also known as NextDext®). Consumption of prebiotic fiber may have several beneficial effects on digestive health, e.g. it can increase satiety, controls hunger hormones (e.g. enhances ghrelin and suppresses PYY), improves glycemic control, has laxative effects, can increase stool frequency and has a role in maintaining transit regularity. Therefore, including prebiotic fiber in a composition according to the invention may have an advantageous effect on the reduction of fat accumulation. A composition according to the invention may further comprise a medium chain triglyceride (MCT) oil. An MCT oil is an oil which is mainly in the triglyceride form and containing mainly capryc (C8:0) and caprylic (C10:0) fatty acids. The MCT oil may be prepared by an esterification process between glycerol and fatty acids in their free, methyl ester or ethyl ester form. An example of a preferred MCT oil is ABB I4. MCT oil generally is digested rapidly and represents a rapid source of energy. Rather than being stored as body fat, MCT oil increases satiety, increase the body’s ability to burn fat and calories, which may turn into less fat accumulation. Therefore, including MCT oil in a composition according to the invention may have an advantageous effect on the reduction of fat accumulation. Administration mode and formulations of a physiologically acceptable composition The physiologically acceptable composition of the present invention is preferably administered into the gastrointestinal tract. Administration into the gastrointestinal tract is preferably orally. In a specific embodiment, the composition is administered by tube feeding or as a suppository. Formulations of a composition according to the invention suitable for oral intake include but are not limited to: capsules, coated capsules, tablets, sachets, pills, pearls, softgels, vials, powders, granules, solutions, suspensions, emulsions, elixirs, syrups, sprays, lozenges, troches, gums, hard candies and gels. Topical administration in the treatment of a metabolic disorder generally comprises administration at mucosa or epithelium of the gastro-intestinal tract. A medical product comprising the composition (for use) according to the invention can be a product suitable to create a protective biofilm or the like at the surface of the gut epithelium. Such product can be based for instance on known products for treatment of obesity. In a specific embodiment, the composition is to be administered as a sustained release product. The composition according to the invention may be a food product. The food product may be a fermented food product or a non-fermented food product. Examples of a particularly suitable food products include dairy products such as a yogurt, a yogurt drink, cheese, milk, milk powder, infant formula, cream, ice- cream, cream powder and butter; fruit-based products such as fruit juice, compote or fruit jelly; solid foodstuffs such as flours, bread, cereals, a cereal bar, a snack, a biscuit, a chocolate, a powder for a beverage, and liquid formulations such as ready-to-drink beverages, vegetable beverages, smoothies, isotonic drinks, salts solutions and enteral nutrition recipes. The physiologically acceptable composition according to the invention for intake by an animal may be any appropriate food product for animals and include, in addition to the food products listed above, tablets, coated tablets, granules, cereal grains, (dried) meat, (dried) fish, oil meals, cakes, cookies, sugarcane, and roughages such as grasses, hays, silage, root crops, straw and stover. A food product according to the invention, such as a weight management food product, usually comprises at least one component selected from proteinaceous matter (amino acids, peptides, proteins), lipids (triglycerides etc) and digestible carbohydrates (digestible sugars, oligosaccharides, polysaccharides). Further one or more components selected from the group of dietary fibres, minerals, vitamins, colouring agents, thickening agents, flavouring agents, sweeteners, acidity regulators, antioxidants, stabilizers, emulsifiers and salt are preferably present. Additionally, a food product according to the invention may comprise one or more ingredients selected from the group of water, milk, oil, butter and rice. The nutritional product according to the invention may be in the form of a dietary supplement, a food additive, a feed additive, a functional food in human nutrition, a functional food in animal nutrition, a food additive or functional ingredient for nutraceuticals or food for special medical purposes. The physiologically acceptable composition according to the invention can be a pharmaceutical product, a cosmeceutical product or a nutraceutical product. Said pharmaceutical product may further comprise a pharmaceutically acceptable adjuvant and / or excipient. Adjuvants and excipients are well known to a person skilled in the art. A food product according to the invention may have a high fiber content such as a fiber content of between 5-50 g per 100 g of the total product, making the product highly satiating. A food product according to the invention preferably has a low fat content such as a fat content between 0-20 g per 100 g of the total product. The protein content of a food product according to the invention may vary within wide limits, but preferably is between 1-60 g per 100 g of the total product. A food product according to the invention preferably has a low carbohydrate content such as a carbohydrate content between 0-50 g per 100 g of the total product. The caloric value of a food product according to the invention may vary within wide limits, preferably a food product according to the invention has a caloric value of about 10- 500 kcal per 100 g. Preferably, a food product according to the invention has a low glycemic index (GI) and / or low glycemic load (GL). The GI is a measure of the blood glucose-raising potential of the carbohydrate content of a food product compared to a reference food product, generally pure glucose. To determine the GI of a food product, healthy volunteers are typically given a test food product that provides a certain amount, such as e.g. 50 grams (g), of carbohydrate and a control food (e.g. white bread or pure glucose) that provides the same amount of carbohydrate, on different days. Blood samples for the determination of glucose concentrations are taken prior to eating, and at regular intervals for a few hours after eating. The changes in blood glucose concentration over time are plotted as a curve. The GI is calculated as the incremental area under the glucose curve (iAUC) after the test food is eaten, divided by the corresponding iAUC after the control food is eaten. The value is multiplied by 100 to represent a percentage of the control food. Carbohydrate- containing foods can be classified as high- (i.e. GI ≥70), moderate- (i.e. GI of 56-69), or low-GI (i.e. GI ≤55) relative to pure glucose (i.e. GI GI=100). The GL is a measure used to simultaneously describes the quality (GI) and quantity of carbohydrate in a food product, meal, or diet. The GL of a single food product is calculated by multiplying the GI by the amount of carbohydrate in grams (g) provided by a food serving and then dividing the total by 100. In general for a certain food product, GL is considered high with GL≥20, intermediate with GL of 11-19, and low with GL≤10. High GI or high GL diets have been associated with a higher risk for the development of disorders such as type 2 diabetes and cardiovascular disease. The GL or GI of a food product can be lowered by increasing the amount of whole grains, nuts, legumes, fruit, and non-starchy vegetables, and decreasing the amounts of moderate- and high-GI components such as rice and sugar. An example of a food product according to the invention is a cereal barcomprising Lactiplantibacillus plantarum, tyndallized K. marxianus andinactivated (such as tyndallized) S. boulardii; and further one or more components selected from the group consisting of fibers (e.g. soluble corn fiber and / or chicory root fiber), vitamins (e.g. A, D, E, K, B1, B2, B3, B5, B6, folic acid, biotine and / or B12), milk proteins, vegetable glycerine, butter (e.g. cacao butter, hazelnut butter and / or clarified butter), minerals (potassium, magnesium, iron, copper, manganese, zinc, chlorine and / or iodine), emulsifier (e.g. lecithin), sweeteners (e.g. steviol glycoside and / or maltitol), nuts (e.g. hazelnuts), salt and natural flavourings. Such cereal bar may have a caloric value of about 367 kcal per 100 g, a fat content of about 18 g per 100 g, a carbohydrate content of about 28 g per 100 g, a fiber content of about 20 g per 100 g and a protein content of about 22 g per 100g. Another example of a food product according to the invention is a ready-to-drink smoothie comprising Lactiplantibacillus plantarum, tyndallized K.marxianus and tyndallized S. boulardii; and further one or more components selected from the group consisting of water, milk (e.g. semi-skimmed milk and / or coconut milk), milk protein, vegetable oils (e.g. rapeseed and / or sunflower oil), fibers (e.g. soluble corn fiber and / or oat fiber), rice powder (e.g. rice flour, rice starch and / or rice syrup), maltodextrin, vitamins (e.g. A, D, E, K, B1, B3, B5, B6, folic acid and / or biotine), minerals (e.g. magnesium, iron, copper, manganese, selenium, chromium, molybdenum and / or iodine), emulsifier (e.g. lecithin), sweeteners (e.g. sucralose), stabiliser (e.g. gellan gum), processed euchema seaweed, lactase, salt and natural flavourings. Such smoothie may have a caloric value of about 100 kcal per 100 g, a fat content of about 4.7 g per 100 g, a carbohydrate content of about 6.8 g per 100 g, a fiber content of about 1.6g per 100 g and a protein content of about 6.8 g per 100g. The production of a physiologically acceptable composition The physiologically acceptable composition can be made by combining the different components based on methodology known for making probiotic preparation. For instance for the production of yeasts as comprised in a composition according to the invention, all yeasts may be produced from a non-GMO yeast strain. A fermentation process known per se for the yeast of interest can be used to produce a primary grown, yeast whose growth occurs under aseptic, aerobic conditions. The resulting product, or yeast cream may be held in refrigerated storage to maintain cell viability, if desired. The yeast cream can be subjected to an inactivation treatment, such as a high temperature sterilization or tyndallization to obtain a heat-treated version of the yeast. If desired, the yeast can be dried, for instance by spray drying, which preferably is done after inactivation (if non-viable yeast is to be used for the composition). For instance for the production of bacteria as comprised in a composition according to the invention the bacteria may be produced from a non-GMO bacterial strain. A fermentation process known for the bacteria of interest can be used to produce a primary grown, bacteria whose growth occurs under aseptic, aerobic conditions. The resulting product, can be subjected to an inactivation treatment, such as a high temperature sterilization or tyndallization to obtain a heat-treated version of the bacteria. The bacteria can be dried, for instance by spray drying, to stabilize the cell counts along shelf life. Maltodextrin or other bulking agents can be used as support agent to have standardized concentrations. The bacteria and yeasts are mixed, which mixing may be followed by a homogenization step. Therapeutic and cosmetic uses of the physiologically acceptable composition In accordance with the invention, the physiologically acceptable composition is advantageously used in treating or preventing a medical disorder related to a dysregulated lipid metabolism, in particular in treating or preventing a metabolic disorder, such as overweight, obesity, type 2 diabetes, insulin resistance, metabolic syndrome, hypercholesterolemia, hyperlipidaemia, hypertension, cardiovascular disease, lipodystrophy, lipohypertrophy and combinations thereof. Preferably, a metabolic disorder selected from the group consisting of overweight, obesity, metabolic syndrome is treated. It is well-known that some patients do not achieve optimal weight loss or regain weight after bariatric surgery. Therefore, the physiologically acceptable composition of the invention may be used as an adjuvant to bariatric surgery, wherein it may be administered prior to surgery or after surgery. Further, the physiologically acceptable composition is advantageously used in the prevention or treatment of an individual with a high abdominal fat level and in particular a high visceral fat level. It has been shown that overweight individuals with high visceral fat levels have more associated morbidities or experience more severe morbidities. Additionally, high visceral fat levels are a predictor for coronary disease and increased cardiovascular risk. Methods to measure visceral fat levels are known to a person skilled in the art and include imaging methods such as magnetic resonance (MR) or computed tomography (CT) scanning. Alternatively, the determination of the visceral fat level of an individual can be done indirectly, by determining one or more anthropometric or clinical indicators that have been shown to be associated with visceral fat level. Such indicators include weight, body mass Index (BMI), waist circumference (WC), hip circumference (HC); waist-to-hip ratio, waist-to-height ratio, waist-to-thigh ratio, sagittal abdominal diameter (SAD), abdominal diameter height index (SAD / Height), abdominal diameter index (ADI), conicity index (CI), visceral adiposity index (VAI) and the lipid accumulation production (LAP). A person skilled in the art knows how to determine these indicators and their association to visceral fat level, by using standard referencessuch as e.g Roriz et al. (Roriz et al., 2016. Nutr clín diet hosp 36: 168-179).Further, the physiologically acceptable composition according to the invention is particularly suitable to reduce fat deposition and fat accumulation and to promote weight loss in an individual, wherein the individual has a BMI of 25 kg / m2or higher. Further, the physiologically acceptable composition is advantageously used in the prevention or treatment of an individual with a disorder defined by markers that are characteristic for a dysregulated lipid metabolism, such markers include blood lipids apoB and apoA1, satiety hormones, glycemic parameters and inflammatory parameters . Disorders defined by such markers that are treated by the invention include overweight, obesity, type 2 diabetes, insulin resistance, metabolic syndrome, hypercholesterolemia, hyperlipidaemia, hypertension, cardiovascular disease, lipohypertrophy and lipodystrophy. In particular, the physiologically acceptable composition of the invention is suitable for the treatment of metabolic disorders defined by one or more of said markers. A medical use according to the invention is in particular advantageous for use in an individual that has a medical disorder associated with bodyweight, lipid metabolism or the like. Preferably, a medical use according to the invention is for the treatment of an individual having a disorder selected from the group of overweight, obesity, type 2 diabetes, insulin resistance, metabolic syndrome, hypercholesterolemia, hyperlipidaemia, cardiovascular disease and hypertension. Preferably, a medical use according to the invention is for the treatment of an individual having one or more markers that are characteristic for a dysregulated lipid metabolism such as blood lipids apoB and apoA1, satiety hormones, glycemic parameters and inflammatory parameters. A medical use according to the invention can be directed at treating an individual for prophylactic reasons, in particular if the individual is at risk of developing a medical disorder involving overweight, fat accumulation or fat deposition, such as mentions above. In particular, a prophylactic use according to the invention can be for reducing the risk of developing a disorder selected from the group consisting of overweight, obesity, type 2 diabetes, insulin resistance, metabolic syndrome, hypercholesterolemia, hyperlipidaemia, cardiovascular disease and hypertension. Furthermore, the physiologically acceptable composition according to the invention can be cosmetically used to increase or maintain metabolic rate, decrease percent body fat, increase or maintain muscle mass or manage body weight. The administration dosage, duration and frequency can be chosen within wide limits, dependent on the intended purpose and the subject to whom the composition is to be administered. The duration of treatment can be a relatively short period, e.g. of a month or less, as a preparation for other medical interventions including bariatric surgery, hemodynamic measurements, etc. The duration of a treatment can also be prolonged, e.g. for some a months or more or a year or more, e.g. in case of a chronic disorder such as obesity or diabetes or in case of weight maintenance in case of healthy individuals. The physiologically acceptable composition for use according to the invention may be administered as multiple dosage. The number of dosages is generally 5 times per day or less. E.g. more than 3 dosages per day may be administered, but typically it is administered about 3 time per day or less, preferably about 2 times per day or less, in particular about once per day or less. In an embodiment, the composition is administered (on average) at least about once a week. Preferably, it is administered (on average) at least once per period of three days, more preferably (on average) at least once per period of two days. The physiologically acceptable composition may comprise or can be co- administered with a(nother) probiotic, a prebiotic, a postbiotic, an antibiotic, an analgesic, an herbal product, an(other) weight loss or anti-obesity agent such as naltrexone, bupropion, liraglutide, locarserin, orlistat, phentermine or topiramate among others, or a mixture thereof. It may be administered as adjuvant to bariatric surgery. The physiologically acceptable composition may be combined with lifestyle modifications including nutritional interventions, increased physical activity and behavioural therapy. A person skilled in the art will be able to determine an appropriate dose of the physiologically acceptable composition to administer to an individual based on common general knowledge and the information disclosed herein without undue experimentation. As the skilled person will understand, an actual preferred dosage depends on a variety of factors, including the activity of the specific yeasts and bacteria employed, the metabolic stability and length of action of that yeast or bacterium, the age, body weight, general health, sex and species of the individual diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular disorder, and the individual. The dosages disclosed herein are indicative of an average case for a human individual. There can of course be individual instances where higher or lower dosage ranges are merited. The usual effective daily dose for oral administration or other administration into the gastrointestinal tract, in particular for humans, is from about 20 mg (of the microbiological components) to about 1000 mg (of the microbiological components), preferably, from about 200 mg (of microbiological components) to about 900 mg (of the microbiological components), more preferably, from about 200 mg (of the microbiological components) to about 650 mg (of microbiological components). The invention provides a physiologically acceptable composition for use as a medicament. The invention provides a method of treating an individual with a dysregulated lipid metabolism, comprising the administration of an effective amount of the physiologically acceptable composition according to the invention, hereby reducing fat deposition or fat accumulation in said individual. The invention provides a method of treating an individual with a metabolic disorder, such as of a disorder such as obesity, type 2 diabetes, insulin resistance, metabolic syndrome, hypercholesterolemia, hyperlipidaemia, cardiovascular disease or hypertension, comprising the administration of an effective amount of the physiologically acceptable composition according to the invention to said individual. The invention provides a method of treating an overweight individual (such as an adult human having a BMI of 25 kg / m2or higher), in particular an obese individual (such as an adult human with a BMI of 30 kg / m2or higher), wherein weight loss is promoted or wherein fat deposition or fat accumulation is reduced, comprising the administration of an effective amount of the physiologically acceptable composition according to the invention to said individual. The invention provides a method of promoting weight loss, for reducing fat deposition or fat accumulation, or managing weight in an individual, comprising the administration of an effective amount of the physiologically acceptable composition according to the invention to said individual. The invention provides the use of the physiologically acceptable composition according the invention for use in the preparation of a product, which may be a medicament or a food product (such as a medical or clinical food), for use in the treatment of a disorder such as overweight, obesity, type 2 diabetes, insulin resistance, metabolic syndrome, hypercholesterolemia, hyperlipidaemia, cardiovascular disease or hypertension. The invention provides the use of the physiologically acceptable composition according the invention for use in the preparation of a product, which may be a medicament or a food product (such as a medical or clinical food), for use in treatment of an overweight individual (such as an adult human having a BMI of 25 kg / m2or higher) or obese individual (such as an adult human having a BMI of 30 kg / m2or higher or BMI of 35 kg / m2or higher), wherein weight loss is promoted or wherein fat deposition or fat accumulation is reduced. The invention provides the use of the physiologically acceptable composition according the invention for use in the preparation of a product, which may be a medicament or a food product (such as a medical or clinical food), for cosmetic use for promoting weight loss in an individual, for reducing fat deposition or fat accumulation, or as a weight management supplement. The invention will now be illustrated by the following examples, which are provided by way of illustration and it will be understood that many variations in the methods described and the amounts indicated can be made without departing from the spirit of the invention and the scope of the appended claims.

[0002] EXAMPLES Example 1: in vivo inhibition of fat deposition (C. elegans model) Materials and methods The strains were cultured in their respective media from powders, streaked out onto MRS agar plates to visually observe any possible contamination. and Glycerol stocks were made from single colonies and kept at -80°C. Concentrations of the bacteria, yeasts, extracts, prebiotics and oils in the combinations were previously pre-defined to optimize visibility under a dissecting microscope. Live bacteria and yeasts were cultured from glycerol stock inoculum, grown in cognate media under appropriate conditions and time. The bacteria were washed and resuspended in M9 Buffer [3 g KH2PO4, 6 g Na2HPO4, 5 g NaCl, 1 ml 1 M MgSO4, H2O to 1 litre. Sterilize by autoclaving]. The live yeasts were resuspended in the supernatant from their liquid cultures in order to retain any metabolites released during growth that may have a beneficial effect on the bacteria or worms. Inactive yeast suspensions were made by resuspending at 20 mg / ml in M9. The different components were mixed at appropriate amounts in a final volume of 105 – 110 µL, in order to add 100 µL to agar plates, which contained Defined Media without amino acids* to limit the growth of the microbes. DM-a / a media was prepared by adding agar at 2% and NaCl at 0.3% to distilled water and autoclaving at 121°C for 20 minutes. Once media had cooled to 55°C, the following solutions were added: 1M Magnesium Sulphate at 0.1%, 1M Potassium Phosphate buffer pH 6 at 2.5%, Cholesterol stock solution (5mg / ml, dissolved in ethanol) at 0.1%, Trace metals stock solution at 0.02% (Maynard et al 2018 BMC Biology), 100 µM Vitamin B12 stock solution at 0.01%, Uracil stock solution (2mg / ml dissolved in distilled water and filter sterilized) at 0.2%. Each petri dish was filled with 15 ml of media. Plates were left to dry for 18-20h at 24ºC and were inspected visually for homogeneity and opacity before worms were added. The next day, thirty age- synchronised juvenile C. elegans (L4 larvae) wild type worms (N2 strain) were added to each plate and kept at 24°C. 5 plates of 30 worms were set up per condition. For quantifying fat deposition, Oil Red staining protocol adapted from Escorcia et al 2018 J Vis Exp. 2018; (133): 57352 was used. Optimisation of this protocol was performed using SS104 worms from starved vs unstarved plates. ORO (Oil Red O) working solution made by diluting ORO stock solution (0.5% Oil Red O solution in isopropanol, SIGMA) 3:2 to 60% isopropanol and mixed overnight. The working solution is filtered through a 0.22um PES filter before using (0.2 µm cellulose acetate filters can also be used). After 4 days, worms were washed in M9-Tween (M9-T) and fixed by adding 600 μl, 40% isopropanol and rocking at room temperature for 3 minutes. The worms are fixed within 15 min of washing. Worms are settled by spinning at 500 rpm, 30 sec. and fix was removed so that 100 μl remains. 600 μl ORO working solution (see above) is added and tubes inverted so that the worms mix well in ORO solution. The tubes are rocked at 40 rpm on shaker at 24°C for 2 hours, then spun at 500 rpm for 1 min. Supernatant is then removed taking care that settled worms are not removed. Staining solution is removed till 100 μl remains.600 μl of M9-T is added and tubes rocked at 40 rpm on shaker at 24°C for 30 min. Worms are settled by spinning 500 rpm for 1 min and the supernatant removed so that 50 μl remains. The tubes are kept at 4°C overnight. Stained worms are imaged on the brightfield microscope. A minimum of 90 worms per condition were imaged. Measurement of Oil red O intensity as analogue digital units (ADUs) were performed using Image J as follows: The images were converted to RGB and using the blue channel the outlines of the worms were selected and the mean intensity was measured. The background mean intensity was also measured and absorbance was calculated as A=1- (worm intensity / background intensity). The analysis was performed using Microsoft Excel and a one-way ANOVA test was used for statistical analysis. Results The effect of different yeasts and yeast combinations added to a bacterial food source (i.e. Lactiplantibacillus plantarum, ABB S20) was studied by measurement of Oil Red O (ROR) intensity as analogue digital units (ADUs) using Image J in stained C. elegans worms (Figure 1). The standard feed E. coli OP50 was taken along as a positive control. A significant reduction of fat deposition was observed when adding the following to L. plantarum (ABB S20): live K. marxianus (ABB S7) alone; live K. marxianus (ABB S7) and live S. boulardii (ABB S1); live K. marxianus (ABB S7) and prebiotic fiber Dextran (ABB I5); live K. marxianus (ABB S7) and MCT oil (ABB I4); tyndallized K. marxianus (ABB S8) and tyndallized S. boulardii (ABB S3); and tyndallized K. marxianus (ABB S8) and MCT oil (ABB I4). Preferably, the reduction in fat deposition is unrelated to the development of C. elegans. Therefore, the combination of tyndallized K. marxianus (ABB S8) and tyndallized S. boulardii (ABB S3) added to Lactiplantibacillus plantarum ABB S20 is a preferred combination. This combination resulted in a reduction in fat deposition without affecting the development of the C. elegans (Figure 2).

Claims

Claims 1. A physiologically acceptable composition comprising (i) at least one bacterium or a component, lysate or extract thereof, wherein the bacterium is selected from the group of Lactiplantibacillus, Lactobacillus and Bifidobacterium, and further comprising (ii) at least one component selected from the group consisting of K. marxianus yeasts, K. marxianus lysates, K. marxianus cell wall components and K. marxianus extracts.

2. The physiologically acceptable composition according to claim 1, wherein the bacterium is a Lactiplantibacillus plantarum, preferably the bacterium is L. plantarum ABB S20 as deposited with the National Measurement Institute (Victoria, Australia) under accession number V23 / 013536 or a derivative strain thereof.

3. The physiologically acceptable composition according to any of claims 1-2, comprising K. marxianus yeast, wherein at least part of said yeast is inactivated, preferably heat-killed, more preferably tyndallized.

4. The physiologically acceptable composition according to any of the preceding claims, wherein the bacterium, preferably Lactiplantibacillus plantarum, is present in a concentration of at least 106cells per gram (based on total weight of the yeast and bacterial components)¸ preferably from 108cells per gram (based on total weight of the yeast and bacterial components) to 5x1010cells per gram (based on total weight of the yeast and bacterial components) and wherein K. marxianus is present in a concentration of at least 106cells per gram¸ preferably 108cells per gram (based on total weight of the yeast and bacterial components) to 5x1010cells per gram (based on total weight of the yeast and bacterial components).

5. The physiologically acceptable composition according to any of the preceding claims, further comprising at least one component selected from the group consisting of S. boulardii yeasts, S. boulardii lysates, S. boulardii cell wall components, and S. boulardii extracts.

6. The physiologically acceptable composition according to any of claims 5, comprising S. boulardii yeast, wherein at least part of said yeasts is inactivated, preferably heat-killed, more preferably tyndallized.

7. The physiologically acceptable composition according to claim 5 or claim 6, wherein the S. boulardii is present in a concentration of at least 106cells per gram(based on total weight of the yeast and bacterial components)¸ preferably 109cells per gram (based on total weight of the yeast and bacterial components) to 5x1010cells per gram (based on total weight of the yeast components).

8. The physiologically acceptable composition according to any of claims 1-7, wherein the composition is a pharmaceutical product, a nutraceutical product or a cosmeceutical product.

9. The physiologically acceptable composition according to any of claims 1-7, wherein the composition is a food product, preferably a food product selected from the group consisting of dairy products, fruit-based products, cereal products, snacks, powders for a beverage, ready-to-drink beverages, vegetable beverages, smoothies, isotonic drinks and weight management food products, more preferably a weight management food product.

10. The physiologically acceptable composition according to any of the preceding claims, comprising K. marxianus yeast, which yeast is of a strain of which arepresentative sample of which has been deposited with the NationalMeasurement Institute (Port Melbourne, Victoria, Australia) under accession numberV21 / 012435 or a derivative strain thereof; the composition further comprising L. plantarum bacterium, which bacterium is of a strain of which a representative sample has been deposited with the National Measurement Institute (Port Melbourne, Victoria, Australia) under accession number V23 / 013536 or a derivative strain thereof.

11. The physiologically acceptable composition according to claim 10, the composition further comprising S. boulardii yeast, which S. boulardii is of a strain of which a representative sample has been deposited with the Leibniz Institute DSMZ – German Collection of Microorganisms and Cell Cultures GmbH (Braunschweig, Germany) under accession number DSM 33954 or a derivative strain thereof.

12. The physiologically acceptable composition according to any of the preceding claims, comprising L.plantarum lysate, K. marxianus lysate and optionally viable S. boulardii lysate.

13. The physiologically acceptable composition according to any of the preceding claims, for use in the treatment of an individual by therapy, wherein the individual is a human or animal.

14. The physiologically acceptable composition for use according to claim 13, wherein weight loss is promoted or wherein fat deposition or fat accumulation is reduced, and wherein the individual is an adult human having a Body Mass Index (BMI) of 25 kg / m2or higher, such as a BMI of 30 kg / m2or higher or a BMI of 35 kg / m2or higher.

15. The physiologically acceptable composition for use according claims 13 or 14, for use in the treatment of a medical disorder selected from the group consisting of overweight, obesity, type 2 diabetes, insulin resistance, metabolic syndrome, hypercholesterolemia, hyperlipidaemia, cardiovascular disease and hypertension.

16. The physiologically acceptable composition for use according to any of the claims 13-15, wherein the composition is to be administered into the gastrointestinal tract, preferably orally.

17. The physiologically acceptable composition for use according to any of the claims 13-16, wherein fat deposition or fat accumulation in the body of said human or animal is reduced.

18. The physiologically acceptable composition for use according to any of the claims 13-17, wherein the composition is co-administered with a probiotic, a prebiotic, a postbiotic, an antibiotic, an analgesic, an herbal product, an anti- obesity agent such as naltrexone, bupropion, liraglutide, locaserin, orlistat, phentermine or topiramate among others, or a mixture thereof.

19. The physiologically acceptable composition for use according to any of the claims 13-18, for use as adjuvant to bariatric surgery.

20. Use of a physiologically acceptable composition according to any of the claims 1-12 as a food additive, a feed additive, a functional food in human nutrition, a functional food in animal nutrition, a food additive or functional ingredient for nutraceuticals.

21. Use of a physiologically acceptable composition according to any of the claims 1-12 as a probiotic, a postbiotic, a paraprobiotic, a prebiotic, a symbiotic or a probiotic-substitute.

22. Cosmetic use of a physiologically acceptable composition according to any of the claims 1-12 for promoting weight loss in an individual, for reducing fat deposition or fat accumulation, or as a weight management supplement.

23. Cosmetic use of a physiologically acceptable composition according to claim 22, wherein the individual is an adult human having a BMI in the range of 18.5-25, in particular 20-25.

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