Probiotics for treating tumors

Abstract

The present invention relates to a method for treating conditions associated with weight loss in emaciation and cachexia with a probiotic composition and the use of a probiotic composition in the treatment of conditions associated with weight loss in emaciation and cachexia. The present invention provides a method of treating a condition associated with weight loss, the method comprising administering to a subject considered in need of such treatment a probiotic composition wherein the composition comprises at least two bacteria, each preferably selected from a different genus, the genus is preferably selected from the group consisting of Lactobacillus genus, Enterococcus genus and Bifidobacterium genus. The present invention also provides a probiotic composition for use in the treatment of a subject suffering from a condition associated with weight loss wherein the composition comprises at least two bacteria each preferably selected from a different genus, preferably selected from the group consisting of Lactobacillus genus, Enterococcus genus and Bifidobacterium genus.

Description

Technical Field

[0001] The present invention relates to methods of treating weight loss-related conditions in wasting and cachexia with a probiotic composition and the use of a probiotic composition in treating weight loss-related conditions in wasting and cachexia. Background Art

[0002] Skeletal muscle wasting occurs in a variety of diseases, including diabetes, cancer, Crohn's disease, chronic obstructive pulmonary disease (COPD), disuse, and denervation (Zhou et al., Cytokine Signaling in Skeletal Muscle Wasting, Trends in Endocrinology & Metabolism, 2016, 27; 335-347). Muscle wasting is a frequently observed condition that leads to progressive functional impairment, psychological distress, and reduced overall resilience (Lenk, K.; Schuler, G.; Adams, V. Skeletal muscle wasting incachexia and sarcopenia: Molecular pathophysiology and impact of exercise training. J. Cachexia Sarcopenia Muscle 2010, 1, 9–21). Normally, the balance between protein synthesis and breakdown is tightly regulated and influenced by external stimuli such as physical activity and protein intake. However, during muscle wasting, this balance shifts toward muscle protein breakdown, often due to inflammation, whether disease-induced or age-induced. These inflammation-related muscle wasting syndromes are often referred to as cachexia and sarcopenia, respectively. Because chronic inflammatory diseases such as cancer primarily develop in the elderly, sarcopenia and cachexia can also occur simultaneously (Pan et al., Inflammation and sarcopenia: A focus oncirculating inflammatory cytokines, Experimental Gerontology, 154, 2021, 111544). Cachexia is often misdiagnosed as a simple condition of weight loss, but is actually a highly complex metabolic disorder involving features of anorexia, anemia, lipolysis, and insulin resistance (Saini A, Al-Shanti N, Stewart CE. Waste management - cytokines, growth factors and cachexia. Cytokine Growth Factor Rev. 2006 Dec;17(6):475-86). Such conditions can lead to a significant loss of lean body mass, resulting in skeletal muscle wasting. Unlike starvation, weight loss in chronic diseases is also due to a loss of muscle and fat. The cachectic state is particularly problematic in cancer, typically with a poor prognosis and often reduced response to chemotherapy and radiotherapy. More than half of cancer patients suffer from cachexia (also referred to herein as cancer-induced cachexia or tumor-induced cachexia or cancer-related cachexia or tumor-related cachexia), and remarkably, nearly one-third of cancer deaths are related to cachexia rather than tumor burden. As stated by Al-Zoughbi et al. (Tumour macroenvironment andmetabolism. Semin Oncol. 2014 Apr;41(2):281-95.), cancer-related cachexia is the most important tumor-related systemic syndrome in advanced malignant disease and not only affects the quality of life of patients with various malignancies but is also estimated to be the cause of death in 15%-20% of all cancer patients.

[0003] Cachexia is associated with infection, decubitus ulcers, and even death. A multivariate analysis of risk and prognostic factors for community-acquired pneumonia in older adults found that age alone was not a significant factor associated with prognosis. Among the significant risk factors, only nutritional status is amenable to medical intervention. Cachexia in older adults can have profound consequences: medical, cognitive, and psychiatric symptoms can reduce independence in activities of daily living, thereby diminishing quality of life and increasing the frequency of secondary surgeries, hospitalizations, and the need for skilled nursing care. Cachexia is often associated with elevated levels of tumor necrosis factor alpha (TNF-α), interleukin (IL) 1, IL-6, serotonin, and interferon gamma. These proinflammatory cytokines have been shown to play a role in cancer cachexia. Decreased levels of these cytokines are associated with weight gain. Furthermore, with recent advances in cancer therapy, patients are often living longer and, therefore, improving the quality of life during this period is crucial. In this context, treatment options targeting specific and often systemic complications of advanced malignant disease are needed. The gut microbiome is composed of a complex community of 100 trillion intestinal archaea and over 1,000 bacterial cells of different species. These bacteria have unique metabolisms that result in the production of metabolites and microbiome-associated molecular patterns. Some of these metabolites are secreted into the host's feces and are known as fecal volatile organic compounds (VOCs). In the context of cancer, bacterial metabolites may influence a patient's nutrient uptake, metabolism, intestinal motility and barrier function, and systemic inflammatory responses. Consequently, alterations in the gut microbiome composition, associated with increased proinflammatory cytokines and a catabolic state, have been observed in animal models of neoplastic disease.

[0004] Over the past three decades, probiotics have become an increasingly popular research topic. Defined as "live microorganisms that confer a health benefit on the host when administered in adequate amounts," probiotics have been found to have a variety of local and systemic effects in humans. Research on probiotics and cancer cachexia is still in its infancy, but intriguing new evidence has emerged. Varian et al. recently evaluated the role of Lactobacillus reuteri (L. reuteri) as a probiotic in cancer cachexia (Beneficial Bacteria Inhibit Cachexia. Oncotarget 2016, 7, 11803–11816). Using the widely accepted ApcMIN / + mouse model of colon cancer cachexia, which was administered via drinking water, they found that administration of this lactic, Gram-positive bacterium was associated with greater gastrocnemius muscle mass and reduced evidence of muscle atrophy. Oral administration of L. reuteri was also associated with increased lifespan, thymus enlargement, and decreased expression of FoxN1, a transcription factor involved in systemic inflammation. Bindels et al. are pioneering probiotic trials in patients with cancer cachexia (Synbiotic Approach Restores Intestinal Homeostasis and Prolongs Survival in Leukaemic Mice with Cachexia. ISME J. 2016, 10, 1456–1470). In their study, they noted reduced levels of Lactobacillus reuteri and Lactobacillus johnsonii / gasseri in a cachectic leukemic mouse model. Following oral supplementation with L. reuteri, these mice demonstrated reduced expression of markers of muscle atrophy, particularly in the gastrocnemius and tibialis muscles. They also demonstrated reductions in systemic inflammatory cytokines (IL-6, monocyte chemoattractant protein-1, IL-4, and granulocyte colony-stimulating factor). Separate studies further expanded on this evidence using a symbiotic approach using a probiotic (L. reuteri) and a prebiotic (inulin-type fructan). The effects of this combination were evaluated in mouse models of cancer cachexia, including colon cancer (C26) and leukemia (BaF). Administration of this combination was found to be associated with reduced cancer cell proliferation and muscle wasting. Furthermore, mice treated with Lactobacillus reuteri and inulin-type fructans showed reduced morbidity and prolonged survival (Restoring Specific Lactobacilli Levels Decreases Inflammation and Muscle Atrophy Markers in an Acute Leukemia Mouse Model. PLoS ONE 2012, 7, e37971).However, Lactobacillus reuteri among probiotics is generally considered to carry a risk of negative consequences because it tends to produce histamine, which can be harmful to individuals who are overly sensitive to histamine (Straub et al., Z Lebensm Unters Forsch. 1995 Jul; 201(1): 79-82.). As described by Herremans et al. (The Microbiota and Cancer Cachexia; Int. J. Mol. Sci. 2019, 20, 6267;), research on probiotics continues to develop because they hold promise as a new treatment option for patients with cancer cachexia. Evaluation by Genaro et al. (Probiotic supplementation attenuates the aggressiveness of chemically induced colorectal tumor in rats. Life Sci. 2019 Nov 15;237:116895) Probiotics Chemically induced Colorectal cancer Twenty-five male Fisher 344 rats, 250 g, were provided with feed and water ad libitum and randomly divided into 5 groups (5 rats / group): G 对照 ,not yet deal with ; G 肿瘤 , tumor induction; G 肿瘤+5FU , tumor induction, application of 5-fluorouracil; G 肿瘤+Prob , induce tumors, supplement with probiotics; G 肿瘤+5-FU+Prob , tumor induction, application of 5-fluorouracil, and supplementation with probiotics. For tumor induction, 20 mg / kg of 1,2-dimethylhydrazine was administered over a period of approximately 10 weeks in all rats other than the control group (administered intraperitoneally over 4 weeks, followed by a 15-day interval and then repeated for another 4 weeks). Fifteen weeks after the onset of tumor induction (five weeks after the final dose of the carcinogen), 5-fluorouracil (15 mg / kg, intraperitoneally / week) and / or commercial probiotics (containing Lactobacillus acidophilus, Lactobacillus paracasei, Bifidobacterium lactis and Bifidobacterium bifidum, totaling 1×10 9 CFU, daily / gavage) for 10 weeks. Genaro et al. neither implicitly nor explicitly measured effects on time to tumor onset, time to tumor progression, or tumor-induced cachexia. These researchers first concluded that the approximately 15-week regimen used for tumor induction allowed the development of preneoplastic but aberrant crypt foci (ACFs). They then determined the effects of treatment on established tumors and found (see also Table 1 of Genaro et al.) that treatment with the chemotherapy and / or probiotics resulted in a slight reduction in the aggressiveness of tumor histopathology, as evidenced by a decrease in the number of adenocarcinomas compared with untreated rats with tumor induction, despite a proportional increase in the number of tubular adenomas or carcinomas in situ in treated rats 25 weeks after tumor induction. Notably, less aggressive adenomas or carcinomas in situ replaced more aggressive adenocarcinomas without changing the final total number of tumors per five rats, again suggesting that Genaro et al.'s treatment was not associated with a reduction in time to tumor onset or progression, but rather simply that the reduction in tumor aggressiveness observed in these rats was entirely genuine.

[0005] WO / 2022 / 15797 relates to a nutritional composition consisting of Bifidobacterium breve, Bifidobacterium bifidum, Lactobacillus caucasus, Lactobacillus plantarum, Lactobacillus salivarius, Lactobacillus reuteri, prebiotics such as inulin and transferrin, such as lactoferrin, for the treatment of chemotherapy-related diseases. WO / 2022 / 15797 neither implicitly nor explicitly measures or reports the effects of probiotics on the time to tumor onset, the significant effects on the time to tumor progression, and the effects of chemotherapy on tumor-induced cachexia. Furthermore, WO / 2022 / 15797 specifically teaches that the composition is only supposed to rely on its effect on cachexia when a Lactobacillus reuteri strain is present in the composition, along with prebiotics such as inulin and transferrin, such as lactoferrin.

[0006] WO / 2021 / 138979 is limited to probiotic-mineral composite formulations. Probiotic microspheres are obtained by mixing an anaerobic probiotic culture solution with a mineral material suspension and then continuing the culture. The probiotics are selected from Lactobacillus, Bifidobacterium, Enterococcus faecalis, or Bacillus subtilis; and the mineral material is selected from montmorillonite, diatomaceous earth, kaolin, attapulgite, or clay particles. Furthermore, the invention discloses the use of probiotic-mineral composite formulations, the mineral materials in the preparation of drugs for inhibiting the growth of malignant tumors, and corresponding drugs for inhibiting the growth of malignant tumors. Experiments in mice have shown that the probiotic-mineral composite formulation and the mineral materials alone have an inhibitory effect on malignant tumors. WO / 2021 / 138979 does not disclose that the probiotic composition itself (without the mineral material) has an inhibitory effect on malignant tumors, let alone an effect on any aspect of tumor onset or progression, or an effect on weight loss, emaciation, or cachexia. WO / 2021 / 138979 does not disclose a probiotic mineral material complex formulation, in which a probiotic mixture of at least two different species of Lactobacillus, Bifidobacterium, Enterococcus faecalis or Bacillus subtilis is provided. Summary of the Invention

[0007] The present invention provides a method for treating a condition associated with weight loss in a subject, preferably allowing or inducing an increase in the accumulation of white adipose tissue in the subject, preferably a human subject, the method comprising administering a probiotic composition to a subject deemed in need of such treatment, wherein the composition comprises at least two bacteria, each of the at least two bacteria being preferably selected from a different genus, preferably selected from the group consisting of Lactobacillus (preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus salivarius, or Lactobacillus plantarum), Enterococcus (preferably selected from Enterococcus faecalis or Enterococcus faecium), and Bifidobacterium (preferably selected from Bifidobacterium bifidum or Bifidobacterium lactis). To minimize the effects of histamine, preferably at least one, preferably at least two, more preferably at least three different bacteria, more preferably at least four, and most preferably all five bacteria selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus salivarius, or Lactobacillus plantarum are selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus salivarius, or Lactobacillus plantarum. Compared with selecting Enterococcus faecalis and selecting Enterococcus faecium, the latter is preferred because Enterococcus faecium is considered to have a much lower risk of carrying virulence factors than Enterococcus faecalis (Elsner et al. Eur J Clin Microbiol Infect Dis. 2000 Jan; 19 (1): 39-42). From the group of Bifidobacteria, preferably at least Bifidobacterium lactis is selected, more preferably both Bifidobacterium bifidum and Bifidobacterium lactis. In a preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus and one bacterium selected from the genus Enterococcus. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium. In another and further preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus, one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium.

[0008] In another preferred embodiment, the present invention provides a method of treating a condition associated with weight loss, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, the species being preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis. In another preferred embodiment, the present invention provides a method of treating a weight loss-related condition in a subject, preferably allowing an increase in the accumulation of white adipose tissue in the subject, preferably a human subject, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0009] In another preferred embodiment, the present invention provides a method of treating a condition associated with weight loss, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, the species being preferably selected from the group consisting of Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0010] In another preferred embodiment, the present invention provides a method of treating a condition associated with weight loss, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the composition comprises at least nine different bacteria, the at least nine different bacteria being preferably selected from the group consisting of Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23, and Bifidobacterium lactis W51.

[0011] The present invention provides a method for treating emaciation in a subject, preferably allowing or inducing an increase in the accumulation of white adipose tissue in the subject, preferably a human subject, the method comprising administering a probiotic composition to a subject deemed in need of such treatment, wherein the composition comprises at least two bacteria, each of the at least two bacteria being preferably selected from a different genus, preferably selected from the group consisting of Lactobacillus (preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus salivarius, or Lactobacillus plantarum), Enterococcus (preferably selected from the group consisting of Enterococcus faecalis or Enterococcus faecium), and Bifidobacterium (preferably selected from the group consisting of Bifidobacterium bifidum or Bifidobacterium lactis). To minimize the effects of histamine, preferably at least one, preferably at least two, more preferably at least three different bacteria, more preferably at least four, and most preferably all five bacteria selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus salivarius, or Lactobacillus plantarum are selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus salivarius, or Lactobacillus plantarum. Compared with selecting Enterococcus faecalis and selecting Enterococcus faecium, the latter is preferred because Enterococcus faecium is considered to have a much lower risk of carrying virulence factors than Enterococcus faecalis (Elsner et al. Eur J Clin Microbiol Infect Dis. 2000 Jan; 19 (1): 39-42). From the Bifidobacterium group, preferably at least Bifidobacterium lactis is selected, more preferably both Bifidobacterium bifidum and Bifidobacterium lactis. In a preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus and one bacterium selected from the genus Enterococcus. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus, one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium.

[0012] In another preferred embodiment, the present invention provides a method for treating emaciation, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, the species being preferably selected from the following group: Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum, and Bifidobacterium lactis. In another preferred embodiment, the present invention provides a method for treating wasting, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, the species being preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0013] In another preferred embodiment, the present invention provides a method for treating emaciation, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, the species being preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51. In another preferred embodiment, the present invention provides a method for treating emaciation, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the composition comprises at least nine bacteria, preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0014] The present invention provides a method for treating cachexia in a subject, preferably allowing or inducing an increase in the accumulation of white adipose tissue in the subject, preferably a human subject, the method comprising administering a probiotic composition to a subject deemed in need of such treatment, wherein the composition comprises at least two bacteria, each of the at least two bacteria being preferably selected from a different genus, preferably selected from the group consisting of Lactobacillus (preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus salivarius, or Lactobacillus plantarum), Enterococcus (preferably selected from the group consisting of Enterococcus faecalis or Enterococcus faecium), and Bifidobacterium (preferably selected from the group consisting of Bifidobacterium bifidum or Bifidobacterium lactis). To minimize the effects of histamine, preferably at least one, preferably at least two, more preferably at least three different bacteria, more preferably at least four, and most preferably all five bacteria selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus salivarius, or Lactobacillus plantarum are selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus salivarius, or Lactobacillus plantarum. Compared with selecting Enterococcus faecalis and selecting Enterococcus faecium, the latter is preferred because Enterococcus faecium is considered to have a much lower risk of carrying virulence factors than Enterococcus faecalis (Elsner et al. Eur J Clin Microbiol Infect Dis. 2000 Jan; 19 (1): 39-42). From the group of Bifidobacteria, preferably at least Bifidobacterium lactis is selected, more preferably both Bifidobacterium bifidum and Bifidobacterium lactis. In a preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus and one bacterium selected from the genus Enterococcus. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus, one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium.

[0015] In another preferred embodiment, the present invention provides a method of treating cachexia, said method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein said composition comprises at least eight bacteria, each of said at least eight bacteria being preferably selected from a different species, said species being preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis. In another preferred embodiment, the present invention provides a method of treating cachexia, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the composition comprises bacteria, each of which is preferably selected from a different species, preferably selected from the following group: Lactobacillus acidophilus W55 and / or W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23, Bifidobacterium lactis W51. In another preferred embodiment, the present invention provides a method for treating cachexia, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, the species being preferably selected from the group consisting of Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23, and Bifidobacterium lactis W51. In another preferred embodiment, the present invention provides a method for treating cachexia, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the composition comprises at least nine bacteria, preferably selected from the group consisting of Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62, Lactobacillus plantarum W1, Bifidobacterium bifidum W23, and Bifidobacterium lactis W51.

[0016] The present invention also provides a method for treating a neoplastic disease, the method comprising administering a probiotic composition to a subject deemed in need of such treatment, wherein the composition comprises at least two bacteria, each of the at least two bacteria being preferably selected from a different genus, the genus being preferably selected from the group consisting of Lactobacillus, Enterococcus, and Bifidobacterium. In a preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus and one bacterium selected from the genus Enterococcus. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus, one bacterium selected from the genus Enterococcus, and one bacterium selected from the genus Bifidobacterium.

[0017] In another preferred embodiment, the present invention provides a method for treating a neoplastic disease, said method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein said composition comprises at least eight bacteria, each of said at least eight bacteria being preferably selected from a different species, said species being preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis. In another preferred embodiment, the present invention provides a method for treating a neoplastic disease, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, the species being preferably selected from the following group: Lactobacillus acidophilus W55 and / or W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and / or W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0018] In another preferred embodiment, the present invention provides a method for treating a neoplastic disease, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, the species being preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and / or W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0019] In another preferred embodiment, the present invention provides a method for treating a neoplastic disease, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the composition comprises at least nine different bacteria, the at least nine different bacteria being preferably selected from the group consisting of Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0020] The present invention also provides a method for treating a malignant neoplastic disease, the method comprising administering a probiotic composition to a subject deemed in need of such treatment, wherein the composition comprises at least two bacteria, each of the at least two bacteria being preferably selected from a different genus, the genus being preferably selected from the group consisting of Lactobacillus, Enterococcus, and Bifidobacterium. In a preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus and one bacterium selected from the genus Enterococcus. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus, one bacterium selected from the genus Enterococcus, and one bacterium selected from the genus Bifidobacterium.

[0021] In another preferred embodiment, the present invention provides a method for treating a malignant neoplastic disease, said method comprising administering a probiotic composition to a subject deemed in need of such treatment, wherein said composition comprises at least eight bacteria, each of said at least eight bacteria being preferably selected from a different species, said species being preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis. In another preferred embodiment, the present invention provides a method for treating a malignant neoplastic disease, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, the species being preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0022] In another preferred embodiment, the present invention provides a method for treating a malignant neoplastic disease, the method comprising administering a probiotic composition to a subject deemed in need of such treatment, wherein the composition comprises at least nine different bacteria, the at least nine different bacteria being preferably selected from the group consisting of Lactobacillus acidophilus W55 and / or W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0023] The present invention also provides a method for treating a malignant tumor disease, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the subject can, is or has undergone an anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least two bacteria, each of the at least two bacteria being preferably selected from a different genus, the genus being preferably selected from the following group: Lactobacillus, Enterococcus and Bifidobacterium. In a preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus and one bacterium selected from the genus Enterococcus. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus, one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium.

[0024] In another preferred embodiment, the present invention provides a method for treating a malignant tumor disease, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the subject can be, is or has been undergoing anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, the species being preferably selected from the following group: Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis.

[0025] In another preferred embodiment, the present invention provides a method for treating a malignant tumor disease, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the subject can be, is or has been undergoing anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, the species being preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0026] In another preferred embodiment, the present invention provides a method for treating a malignant tumor disease, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the subject can be, is or has been undergoing anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, the species being preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and / or W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51. In another preferred embodiment, the present invention provides a method for treating a malignant tumor disease, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the subject can be, is or has been undergoing anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, the species being preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0027] The present invention also provides a method for treating a malignant tumor disease, wherein the treatment is also intended to delay the onset of cancer and / or delay the progression of cancer, the method comprising administering a probiotic composition to a subject deemed to be in need of such treatment, wherein the subject may or may not be, is undergoing or has undergone an anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least two bacteria, each of the at least two bacteria being preferably selected from a different genus, the genus being preferably selected from the following group: Lactobacillus, Enterococcus and Bifidobacterium. In a preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus and one bacterium selected from the genus Enterococcus. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus, one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium.

[0028] In another preferred embodiment, the present invention provides a method for treating a malignant tumor disease, wherein the treatment is also aimed at delaying the onset of cancer and / or delaying the progression of cancer, the method comprising administering a probiotic composition to a subject deemed in need of such treatment, wherein the subject may or may not be, is undergoing or has undergone anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, the species being preferably selected from the following group: Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis. In another preferred embodiment, the present invention provides a method for treating a malignant tumor disease, wherein the treatment is also aimed at delaying the onset of cancer and / or delaying the development of cancer, the method comprising administering a probiotic composition to a subject deemed to be in need of such treatment, wherein the subject may or may not be, is undergoing or has undergone anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, the species being preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0029] In another preferred embodiment, the present invention provides a method for treating a malignant tumor disease, wherein the treatment is also aimed at delaying the onset of cancer and / or delaying the development of cancer, the method comprising administering a probiotic composition to a subject deemed to be in need of such treatment, wherein the subject may or may not be, is undergoing or has undergone anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, the species being preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0030] In another preferred embodiment, the present invention provides a method for treating a malignant tumor disease, wherein the treatment is also aimed at delaying the onset of cancer and / or delaying the development of cancer, the method comprising administering a probiotic composition to a subject deemed to be in need of such treatment, wherein the subject may or may not be, is undergoing or has undergone anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, the species being preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0031] The present invention provides a probiotic composition for treating a subject suffering from a condition associated with weight loss, wherein the composition comprises at least two bacteria, each of the at least two bacteria being preferably selected from a different genus, preferably selected from the group consisting of Lactobacillus, Enterococcus, and Bifidobacterium. In a preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus and one bacterium selected from the genus Enterococcus. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus, one bacterium selected from the genus Enterococcus, and one bacterium selected from the genus Bifidobacterium.

[0032] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a condition associated with weight loss, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis.

[0033] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a condition associated with weight loss, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the following group: Lactobacillus acidophilus W55 and / or W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0034] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a condition associated with weight loss, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0035] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a condition associated with weight loss, wherein the composition comprises at least nine bacteria, each of the at least nine bacteria being preferably selected from a different species, preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23, Bifidobacterium lactis W51.

[0036] The present invention also provides a probiotic composition for treating a subject suffering from a wasting condition, wherein the composition comprises at least two bacteria, each of the at least two bacteria being preferably selected from a different genus, preferably selected from the group consisting of Lactobacillus, Enterococcus, and Bifidobacterium. In a preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus and one bacterium selected from the genus Enterococcus. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus, one bacterium selected from the genus Enterococcus, and one bacterium selected from the genus Bifidobacterium.

[0037] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a wasting condition, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis. In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a wasting condition, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the group consisting of Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0038] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a wasting condition, wherein the composition comprises at least eight bacterial species, preferably selected from the group consisting of Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0039] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a wasting condition, wherein the composition comprises at least nine bacterial species, preferably selected from the group consisting of Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0040] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a wasting condition, wherein the composition comprises ten bacterial species, preferably selected from the group consisting of Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0041] The present invention also provides a probiotic composition for treating a subject suffering from a cachexia condition, wherein the composition comprises at least two bacteria, each of the at least two bacteria being preferably selected from a different genus, preferably selected from the group consisting of Lactobacillus, Enterococcus, and Bifidobacterium. In a preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus and one bacterium selected from the genus Enterococcus. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus, one bacterium selected from the genus Enterococcus, and one bacterium selected from the genus Bifidobacterium.

[0042] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a cachexia condition, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis.

[0043] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a cachexia condition, wherein the composition comprises at least nine bacteria, each of the at least nine bacteria being preferably selected from a different species, preferably selected from the group consisting of Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0044] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a cachexia condition, wherein the composition comprises ten bacteria, each of the ten bacteria being preferably selected from a different species, preferably selected from the group consisting of Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0045] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a cachexia condition, wherein the composition comprises ten bacteria, each of the ten bacteria being preferably selected from a different species, preferably selected from the group consisting of Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0046] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a cachexia condition, wherein the composition comprises at least eight bacterial species, preferably selected from the group consisting of Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0047] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a cachexia condition, wherein the composition comprises at least nine bacterial species, preferably selected from the group consisting of Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0048] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a cachexia condition, wherein the composition comprises ten bacterial species, preferably selected from the group consisting of Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0049] The present invention also provides a probiotic composition for treating a subject suffering from a tumor disease condition, wherein the composition comprises At least two bacteria, each of which Preferably selected from different genera, said genera are preferably selected from the group consisting of Lactobacillus, Enterococcus and Bifidobacterium. In a preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus and one bacterium selected from the genus Enterococcus. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus, one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium.

[0050] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a neoplastic disease condition, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis.

[0051] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a neoplastic disease condition, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0052] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a neoplastic disease condition, wherein the composition comprises at least nine bacteria, each of the at least nine bacteria being preferably selected from a different species, preferably selected from the group consisting of Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0053] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a tumor disease condition, wherein the composition comprises ten bacteria, each of the ten bacteria is preferably selected from a different species, and the species is preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0054] The present invention also provides a probiotic composition for treating a subject suffering from a malignant disease condition, wherein the composition comprises at least two bacteria, each of the at least two bacteria being preferably selected from a different genus, preferably selected from the group consisting of Lactobacillus, Enterococcus, and Bifidobacterium. In a preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus and one bacterium selected from the genus Enterococcus. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus, one bacterium selected from the genus Enterococcus, and one bacterium selected from the genus Bifidobacterium.

[0055] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a malignant disease condition, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis.

[0056] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a malignant disease condition, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0057] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a malignant disease condition, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0058] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a malignant disease condition, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0059] The present invention also provides a probiotic composition for treating a subject suffering from a malignant disease condition, wherein the subject can, is or has undergone an anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least two bacteria, each of the at least two bacteria being preferably selected from a different genus, the genus being preferably selected from the following group: Lactobacillus, Enterococcus and Bifidobacterium. In a preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus and one bacterium selected from the genus Enterococcus. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus, one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium.

[0060] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a malignant disease condition, wherein the subject can be, is or has been subjected to anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the following group: Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis. In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a malignant disease condition, wherein the subject can be, is or has been undergoing anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0061] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a malignant disease condition, wherein the subject can be, is or has been undergoing anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0062] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a malignant disease condition, wherein the subject can be, is or has been undergoing anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0063] The present invention also provides a probiotic composition for treating a subject suffering from a malignant disease condition, wherein the treatment is also intended to delay the onset of cancer and / or delay the progression of cancer, wherein the subject may or may not be, is undergoing or has undergone an anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least two bacteria, each of the at least two bacteria being preferably selected from a different genus, the genus being preferably selected from the following group: Lactobacillus, Enterococcus and Bifidobacterium. In a preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus and one bacterium selected from the genus Enterococcus. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium. In another preferred embodiment, the composition comprises at least one bacterium selected from the genus Lactobacillus, one bacterium selected from the genus Enterococcus and one bacterium selected from the genus Bifidobacterium.

[0064] In another preferred embodiment, the present invention provides a probiotic composition for use in treating a subject suffering from a malignant disease condition, wherein the treatment is also aimed at delaying the onset of cancer and / or delaying the progression of cancer, wherein the subject may or may not be, is or has been undergoing an anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis.

[0065] In another preferred embodiment, the present invention provides a probiotic composition for use in treating a subject suffering from a malignant disease condition, wherein the treatment is also intended to delay the onset of cancer and / or delay the progression of cancer, wherein the subject may or may not be, is or has been undergoing an anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0066] In another preferred embodiment, the present invention provides a probiotic composition for use in treating a subject suffering from a malignant disease condition, wherein the treatment is also intended to delay the onset of cancer and / or delay the progression of cancer, wherein the subject may or may not be, is or has been undergoing an anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0067] In another preferred embodiment, the present invention provides a probiotic composition for use in treating a subject suffering from a malignant disease condition, wherein the treatment is also intended to delay the onset of cancer and / or delay the progression of cancer, wherein the subject may or may not be, is or has been undergoing an anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0068] In another preferred embodiment, the present invention provides a probiotic composition for treating a subject suffering from a malignant disease condition, wherein the treatment is also intended to delay the onset of cancer and / or delay the progression of cancer, wherein the subject may or may not be, is or has been undergoing an anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W1, Bifidobacterium bifidum W23, Bifidobacterium lactis W51.

[0069] In yet another preferred embodiment, the present invention provides a method for shortening the time to onset of a tumor in a subject, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the composition comprises at least two bacteria, each of the at least two bacteria being selected from a different genus, preferably selected from the group consisting of Lactobacillus, Enterococcus, and Bifidobacterium. Preferably, the present invention provides a method for shortening the time to onset of a tumor in a subject, the method comprising administering a probiotic composition to a subject believed to be in need of such treatment, wherein the composition comprises bacteria preferably selected from different species, preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum, and Bifidobacterium lactis. Preferably, the composition for reducing the time to tumor onset as provided herein comprises at least eight bacterial species, preferably selected from the following groups: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51, more preferably, the composition comprises at least nine bacterial species, preferably selected from the following groups: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51. Most preferably, the composition comprises ten bacterial species, which are preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51.

[0070] In yet another preferred embodiment, the present invention provides a method for shortening the time to tumor development in a subject, the method comprising administering a probiotic composition to a subject deemed in need of such treatment, wherein the composition comprises at least two bacteria, each of the at least two bacteria being selected from a different genus, preferably selected from the group consisting of Lactobacillus, Enterococcus, and Bifidobacterium. Preferably, the present invention provides a method for shortening the time to tumor development in a subject, the method comprising administering a probiotic composition to a subject deemed in need of such treatment, wherein the composition comprises bacteria, preferably selected from different species, preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum, and Bifidobacterium lactis. Preferably, the composition for reducing the time to tumor development as provided herein comprises at least eight bacterial species, preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51, more preferably, the composition comprises at least nine bacterial species, preferably selected from the following group: Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51, most preferably, the composition comprises ten bacterial species, preferably selected from the group consisting of Lactobacillus acidophilus W55 and W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius 24, Lactobacillus plantarum W62 and W1, Bifidobacterium bifidum W23 and Bifidobacterium lactis W51. Most preferably, the method of shortening the time to onset of a tumor in a subject or shortening the time to progression of a tumor in a subject is applied to a condition in which the subject can, is or has undergone anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy.

[0071] The multispecies probiotic product Eco AAD is a defined multispecies probiotic composition comprising bacterial strains from the genera Lactobacillus, Enterococcus, and Bifidobacterium and is commercially available from Winclove (www.winclove.com; Hulstweg 11, 1032 LB, Amsterdam) and the Institut Allergosan (www.allergosan.com; Gmeinstraße 13, 8055 Graz, Österreich). It contains the following commonly available probiotic strains: Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum, and Bifidobacterium lactis. Neuroblastoma (NB) cell lines are transformed neural crest-derived cells that are capable of immortalized proliferation in vitro and in vivo. These cell lines retain the ability to differentiate into neuronal cell types when treated with various agents (Dimitroulakos J, Squire J, Pawlin G, Yeger H. NUB-7: astable I-type human neuroblastoma cell line inducible along N- and S-type cell lineages. Cell Growth Differ. 1994 Apr;5(4):373-84. PMID: 8043511.) BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 Effects of 1.2 x 10^9 CFU of a probiotic product administered daily for at least 3 weeks on the total weight of white adipose tissue (WAT; g / g body weight) in athymic Hsd:Fox1nu mice receiving subperitoneal implantation of human NB cells (n = 12 / group). Animals in the chemotherapy group received two intraperitoneal doses of 50 mg / kg of CTX chemotherapy on days 8 and 9 after human NB cell administration. A p-value < 0.05 was considered statistically significant.

[0072] Figure 2 Effect of 1.2x10^9 CFU of a probiotic product administered daily for at least 3 weeks on the time to tumor onset (time to first visible tumor, measured in days) in athymic Hsd:Fox1nu mice implanted intraperitoneally with human NB cells (n=12 / group). p-values ​​< 0.05 were considered statistically significant.

[0073] Figure 3Effect of 1.2x10^9 CFU of probiotic product eco-AAD / day for at least 3 weeks on total tumor development time (measured in days from subperitoneal implantation to euthanasia) in athymic Hsd:Fox1nu mice receiving subperitoneal implantation of human NB cells (n=12 / group). p-values ​​< 0.05 were considered statistically significant. DETAILED DESCRIPTION

[0074] Cachexia is a multifactorial syndrome defined as weight loss greater than 5%, weight loss greater than 2% in patients with a BMI <20 kg / m², or depletion of skeletal muscle mass. Muscle wasting is an inflammation-driven condition frequently observed in aging and disease, termed sarcopenia and cachexia, respectively. Current therapeutic strategies directly target muscle and generally fail to reverse this process. Because reduced intestinal function is associated with systemic inflammation, this could be an indirect target for ameliorating muscle wasting, treating muscle wasting with pre-, pre-, and synbiotic α, and elucidating which metabolites and mechanisms influence organ crosstalk in cachexia. Collectively, studies have demonstrated that multiple Lactobacillus species (spp.), and possibly other genera such as Bifidobacterium, can ameliorate muscle wasting in mouse models. The beneficial effects of Lactobacillus supplementation may be attributed to their potential to improve microbiome balance and reported ability to reduce intestinal permeability.

[0075] Cachexia is present in approximately 80% of patients with advanced cancer and reportedly contributes to 30% of cancer deaths (Kalantar-Zadeh, K.; Rhee, C.; Sim, J.; Stenvinkel, P.; Anker, S.; Kovesdy, C. Why Cachexia Kills: Examining the Causality of Poor Outcomes in Wasting Conditions. J. Cachexia Sarcopenia Muscle 2013, 4, 89–94.). The clinical manifestations of cachexia have been recognized for centuries, first described by Hippocrates as "a wasting away of the flesh, with incapacity of the shoulders, clavicles, chest, and thighs: this disease is fatal." Modern research has elucidated the complex interplay of cytokines, inflammation, and metabolic derangements. Cachexia includes not only weight loss but also white adipose tissue (WAT) depletion, muscle atrophy, and decreased appetite, with these signs preceded by metabolic dysfunction. Cachexia has been noted in many chronic inflammatory conditions, such as acquired immunodeficiency syndrome (AIDS), sepsis, autoimmune disorders, chronic lung disease, and cancer. Cancer cachexia is particularly devastating, as it predicts early death, poor response to chemotherapy, and can even be the direct cause of death. Beyond the sheer magnitude of the disease, cancer cachexia also impacts patients' quality of life. Muscle and fat loss, as well as progressive anorexia, are particularly distressing for patients and their families. Early interventions such as exercise, nutritional supplements, counseling, and medications have proven ineffective. Several different pharmacological therapies have been tested, focusing on appetite stimulants, anabolic agents, and metabolic inhibitors. Short courses of corticosteroids, progesterone analogs, and more recently, cannabinoids have been used to enhance appetite stimulation in patients with cancer cachexia. Theoretical mechanisms of action of anabolic steroids and recombinant growth hormone in muscle anabolism have been evaluated; however, no statistically significant benefit has been found. Metabolic inhibitors are also being investigated for their potential benefits in reducing systemic inflammation. Eicosapentaenoic acid (EPA) is thought to reduce IL-6, but studies have not consistently shown improvement. Additionally, despite its mechanism of action, TNF-α antibodies have not been shown to have any statistically significant benefit in humans.Overall, pharmacological interventions have not shown a significant survival benefit or improvement in quality of life for patients with cancer cachexia (Bruggeman, AR; Kamal, AH; LeBlanc, TW; Ma, JD; Baracos, VE; Roeland, EJ Cancer Cachexia: Beyond Weight Loss. J. Oncol. Pract. 2016, 12, 1163–1171).

[0076] The probiotic product ecoAAD (van der Geest AM, et al, Multispecies probiotics promote perceived human health and wellbeing: insights into the value of retrospective studies on user experiences. Benef Microbes. 2021 Oct11;12(5):413-430.) used in this article is a defined multispecies probiotic composition comprising bacterial strains from the genera Lactobacillus, Enterococcus, and Bifidobacterium and is commercially available from Winclove (www.winclove.com; Hulstweg 11, 1032LB, Amsterdam) and at the Institut Allergosan (www.allergosan.com; Gmeinstraße 13, 8055 Graz, Österreich). It contains the following nine commonly available probiotic strains: Lactobacillus acidophilus W55 and Lactobacillus acidophilus W37, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62 and Bifidobacterium bifidum W23, Bifidobacterium lactis W51. In order to improve the performance, other established probiotic strains can be preferably added thereto, such as preferably Lactobacillus plantarum W1 (=WCFS1) (van den Nieuwboer Met al., Lactobacillus plantarum WCFS1 and its host interaction: a dozen years after the genome. Microb Biotechnol. 2016 Jul; 9(4): 452-65.).

[0077] Neuroblastoma (NB) cell lines are transformed neural crest-derived cells that are capable of indefinite proliferation in vitro and in vivo. These cell lines maintain the ability to differentiate into neuronal cell types when treated with various agents (Dimitroulakos J, Squire J, Pawlin G, Yeger H. NUB-7: a stable I-type human neuroblastoma cell line inducible along N- and S-type cell lineages. Cell Growth Differ. 1994 Apr; 5(4): 373-84. PMID: 8043511).

[0078] Neuroblastoma (NB) is the most common extracranial malignancy in children, with an incidence of 10.7 per million. NB remains distinct from other pediatric solid tumors due to its biological heterogeneity and the spectrum of clinical behavior, ranging from spontaneous regression to highly aggressive metastatic disease unresponsive to standard and investigational anticancer therapies. The gut microbiota consists of a complex community of 100 trillion intestinal archaea and over 1,000 bacterial cells of different species. These bacteria have unique metabolisms that result in the production of metabolites and microbiome-associated molecular patterns. Some of these metabolites are secreted into the host's feces and are known as fecal volatile organic compounds (VOCs). In the context of cancer, bacterial metabolites may influence patients' nutrient uptake, metabolism, intestinal motility and barrier function, and systemic inflammatory responses. Consequently, alterations in the gut microbiome composition, associated with increased proinflammatory cytokines and a catabolic state, have been observed in animal models of leukemia and neuroblastoma.

[0079] With the advancement of modern chemotherapy, the 5-year survival rate for patients with nephropathy has increased to 76%. Cyclophosphamide (CTX) is included in the SIOPN standard (HRNBL1.7 / SIOPEN) chemotherapy for nephropathy. In addition to its effects on tumor growth, chemotherapy can also lead to intestinal barrier dysfunction, significant bacterial translocation, and increased inflammation. Beyond its effects on the intestinal lining, recent studies have also suggested chemotherapy-induced alterations in the intestinal microbiome. Finally, an intact microbiome appears to be crucial for the efficacy of CTX chemotherapy—for example, by influencing the reprogramming of myeloid cells within the tumor microenvironment.

[0080] Study Design Cancer therapy is often associated with severe side effects, such as drug-induced weight loss, also known as chemotherapy-induced cachexia. The purpose of this study was to investigate the effects of a multispecies probiotic (OMNi-BiOTiC® 10 AAD) in a mouse model of chemotherapy. A total of 24 male BALB / c mice were gavage-fed with either the probiotic formulation or water once daily for three weeks. In the third week, the mice received intraperitoneal cyclophosphamide. At euthanasia, organs were dissected, and serum was sampled for cytokine analysis. Tight junction components, myosin light chain kinase, mucins, and apoptosis markers were examined in the ileum and colon using histological analysis and qRT-PCR. Lipolysis was analyzed using enzyme activity assays, Western blot analysis, and qRT-PCR in WAT. The fecal microbiome was measured by 16S rRNA gene sequencing of fecal samples, and fecal volatile organic compounds were analyzed using gas chromatography / mass spectrometry. Probiotic-fed mice exhibited significantly less weight loss and adipose tissue depletion associated with a CGI58-mediated reduction in lipolysis. They showed significantly fewer proinflammatory cytokines and lower intestinal permeability compared to animals not fed probiotics. The colons of probiotic-fed animals showed lower inflammation scores and less goblet cell loss. qRT-PCR revealed no differences in tight junction components, mucins, or apoptosis markers. No differences in microbiome alpha diversity were observed between treatment groups, but differences in beta diversity were observed. Taxonomic analysis showed that the probiotic group had lower relative abundances of Bacillus odorifera and Ruminococcus-UCG014, and higher abundances of Desulfovibrio. VOC analysis did not produce significant differences. The results of this study suggest that oral administration of the multispecies probiotic OMNi-BiOTiC® 10 AAD can alleviate cyclophosphamide-induced chemotherapy side effects.

[0081] Athymic Hsd:Fox1nu mice received intraperitoneal administration of human NB cells (MHH-NB11) (n = 12 / group; NB-AAD versus NB-Aqua) as previously described (Obermüller et al., Nutrients. 2020 Jul 8;12(7):2029). For CTX chemotherapy, a solution containing 10 mg / ml CTX was prepared by the institution's pharmacy. On days 8 and 9 after administration of human NB cells, animals in the chemotherapy group received two intraperitoneal doses of 50 mg / kg CTX chemotherapy (n = 12 / group; CTX-AAD versus CTX-Aqua).

[0082] In this study, 1.2 x 10 9CFU of probiotic product / day. The probiotic product contained the bacteria Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum, and Bifidobacterium lactis. The results are depicted in Figure 1 、 2 and 3.

[0083] Additional embodiments 1. A method of treating a condition associated with weight loss, the method comprising administering to a subject deemed in need of such treatment a multi-species probiotic composition, wherein the composition comprises at least two bacteria, each of the at least two bacteria being preferably selected from a different genus, preferably selected from the group consisting of Lactobacillus, Enterococcus and Bifidobacterium.

[0084] 2. A method of treating a condition associated with weight loss, the method comprising administering to a subject deemed in need of such treatment a multispecies probiotic composition, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria being preferably selected from a different species, the species being preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis. 3. A method of treating a condition associated with weight loss, the method comprising administering to a subject deemed in need of such treatment a multi-species probiotic composition, wherein the composition comprises the species preferably selected from the group consisting of Lactobacillus acidophilus W37, Lactobacillus acidophilus W55, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62, Bifidobacterium bifidum W23, and Bifidobacterium lactis W51. 4. A method of treating a condition associated with weight loss, the method comprising administering to a subject deemed in need of such treatment a multi-species probiotic composition, wherein the composition comprises the species preferably selected from the group consisting of Lactobacillus acidophilus W37, Lactobacillus acidophilus W55, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62, Lactobacillus plantarum W1, Bifidobacterium bifidum W23, and Bifidobacterium lactis W51. 5. A method of treating a condition associated with weight loss, the method comprising administering to a subject deemed in need of such treatment a multi-species probiotic composition, wherein the composition comprises species from the following group: Lactobacillus acidophilus W37, Lactobacillus acidophilus W55, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62, Bifidobacterium bifidum W23, and Bifidobacterium lactis W51. 6. A method of treating a condition associated with weight loss, the method comprising administering to a subject deemed in need of such treatment a multi-species probiotic composition, wherein the composition comprises species from the following group: Lactobacillus acidophilus W37, Lactobacillus acidophilus W55, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62, Lactobacillus plantarum W1, Bifidobacterium bifidum W23, and Bifidobacterium lactis W51. 7. The method according to any one of further embodiments 1 to 6, wherein the condition comprises wasting.

[0085] 8. The method of any one of further embodiments 1 to 7, wherein the condition comprises cachexia.

[0086] 9. The method according to any one of further embodiments 1 to 8, wherein the condition further comprises a tumor disease.

[0087] 10. The method according to any one of further embodiments 1 to 9, wherein the condition is a malignant neoplastic disease.

[0088] 11. The method according to any one of further embodiments 1 to 10, wherein the subject can be, is or has been subjected to anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy.

[0089] 12. The method according to any one of further embodiments 1 to 11, wherein the treatment is also intended to delay the onset of cancer.

[0090] 13. The method according to any one of further embodiments 1 to 12, wherein the treatment is also intended to delay cancer development.

[0091] 14. The method according to any one of further embodiments 1 to 13, wherein the condition is associated with a solid tumor.

[0092] 15. A multi-species probiotic composition for use in treating a subject suffering from a condition associated with weight loss, wherein the composition comprises at least two bacteria, each of the at least two bacteria being preferably selected from a different genus, preferably selected from the group consisting of Lactobacillus, Enterococcus and Bifidobacterium.

[0093] 16. A multi-species probiotic composition for use in treating a subject suffering from a condition associated with weight loss, wherein the composition comprises at least eight bacteria, each of the at least eight bacteria preferably being selected from a different species, preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis. 17. A multi-species probiotic composition for use in treating a subject suffering from a condition associated with weight loss, wherein the composition comprises species preferably selected from the group consisting of Lactobacillus acidophilus W37, Lactobacillus acidophilus W55, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62, Bifidobacterium bifidum W23, and Bifidobacterium lactis W51.

[0094] 18. A multi-species probiotic composition for use in treating a subject suffering from a condition associated with weight loss, wherein the composition comprises species preferably selected from the group consisting of Lactobacillus acidophilus W37, Lactobacillus acidophilus W55, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62, Lactobacillus plantarum W1, Bifidobacterium bifidum W23, and Bifidobacterium lactis W51. 19. A multi-species probiotic composition for treating a subject suffering from a condition associated with weight loss, wherein the composition comprises species from the following group: Lactobacillus acidophilus W37, Lactobacillus acidophilus W55, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62, Bifidobacterium bifidum W23, and Bifidobacterium lactis W51.

[0095] 20. A multi-species probiotic composition for treating a subject suffering from a condition associated with weight loss, wherein the composition comprises species from the following group: Lactobacillus acidophilus W37, Lactobacillus acidophilus W55, Lactobacillus paracasei W20, Lactobacillus rhamnosus W71, Enterococcus faecium W54, Lactobacillus salivarius W24, Lactobacillus plantarum W62, Lactobacillus plantarum W1, Bifidobacterium bifidum W23, and Bifidobacterium lactis W51.

[0096] 21. The probiotic composition according to further embodiments 15 to 20, wherein said condition comprises wasting.

[0097] 22. The probiotic composition of any one of further embodiments 15 to 21, wherein the condition comprises cachexia.

[0098] 23. The probiotic composition according to any one of further embodiments 15 to 22, wherein said condition further comprises a neoplastic disease.

[0099] 24. The probiotic composition according to any one of further embodiments 15 to 23, wherein the condition is a malignant neoplastic disease.

[0100] 25. A probiotic composition according to any one of further embodiments 15 to 24, wherein the subject can be, is or has been undergoing anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy.

[0101] 26. A probiotic composition according to any one of further embodiments 15 to 25, wherein said treatment is further intended to delay the onset of cancer.

[0102] 27. A probiotic composition according to any one of further embodiments 15 to 26, wherein said treatment is further aimed at delaying cancer development.

[0103] 28. A probiotic composition according to any one of further embodiments 15 to 27, wherein the condition is associated with a solid tumor.

Claims

1. A method of treating a condition associated with weight loss, preferably wasting or cachexia, comprising administering a probiotic composition to a subject deemed in need of such treatment, wherein the composition comprises at least two bacteria, each of the at least two bacteria being selected from a different genus, preferably selected from the group consisting of Lactobacillus, Enterococcus and Bifidobacterium.

2. A method of treating a condition associated with weight loss, the method comprising administering a probiotic composition to a subject deemed in need of such treatment, wherein the composition comprises bacteria preferably selected from different species, preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis.

3. The method according to any one of claims 1 or 2, wherein the pathology further comprises, preferably, a malignant tumor disease.

4. A method of shortening the time to onset of a tumor in a subject, the method comprising administering to a subject deemed in need of such treatment a probiotic composition, wherein the composition comprises at least two bacteria, each of the at least two bacteria being selected from a different genus, preferably selected from the group consisting of Lactobacillus, Enterococcus and Bifidobacterium.

5. A method of shortening the time to onset of a tumor in a subject, the method comprising administering to a subject deemed in need of such treatment a probiotic composition, wherein the composition comprises bacteria preferably selected from different species, preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis.

6. A method of shortening the time to tumor development in a subject, the method comprising administering to a subject deemed in need of such treatment a probiotic composition, wherein the composition comprises at least two bacteria, each of the at least two bacteria being selected from a different genus, preferably selected from the group consisting of Lactobacillus, Enterococcus and Bifidobacterium.

7. A method of shortening the time to tumor development in a subject, the method comprising administering a probiotic composition to a subject deemed in need of such treatment, wherein the composition comprises bacteria preferably selected from different species, preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis.

8. The method according to any one of claims 1 to 7, wherein the subject can be, is or has been subjected to an anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy.

9. A probiotic composition for use in treating a subject suffering from a weight loss related condition, preferably wasting or cachexia, wherein the composition comprises at least two bacteria, each of the at least two bacteria being selected from a different genus, preferably selected from the group consisting of Lactobacillus, Enterococcus and Bifidobacterium.

10. A probiotic composition for use in treating a subject suffering from a weight loss related condition, preferably wasting or cachexia, wherein the composition comprises bacteria, each of which is preferably selected from a different species, preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis.

11. The probiotic composition according to any one of claims 9 to 10, wherein the pathology further comprises, preferably, a malignant tumor disease.

12. A probiotic composition for use in a method of shortening the time to onset of a tumor in a subject, the method comprising administering a probiotic composition to a subject deemed in need of such treatment, wherein the composition comprises at least two bacteria, each of the at least two bacteria being selected from a different genus, preferably selected from the group consisting of Lactobacillus, Enterococcus and Bifidobacterium.

13. A probiotic composition for use in a method of shortening the time to onset of a tumor in a subject, the method comprising administering a probiotic composition to a subject deemed in need of such treatment, wherein the composition comprises bacteria preferably selected from different species, preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis.

14. A probiotic composition for use in a method of shortening the time to tumor development in a subject, the method comprising administering a probiotic composition to a subject deemed in need of such treatment, wherein the composition comprises at least two bacteria, each of the at least two bacteria being selected from a different genus, preferably selected from the group consisting of Lactobacillus, Enterococcus and Bifidobacterium.

15. A probiotic composition for use in a method of shortening the time to tumor development in a subject, the method comprising administering a probiotic composition to a subject deemed in need of such treatment, wherein the composition comprises bacteria preferably selected from different species, preferably selected from the group consisting of Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Enterococcus faecium, Lactobacillus salivarius, Lactobacillus plantarum, Bifidobacterium bifidum and Bifidobacterium lactis.

16. A probiotic composition according to any one of claims 9 to 15, wherein the subject can be, is undergoing or has undergone anti-cancer therapy, such as immunotherapy, chemotherapy, radiotherapy and / or surgical therapy.

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