Composition and uses thereof
Patent Information
- Application Number
- AU2025200873
- Authority / Receiving Office
- AU · AU
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2025-02-07
- Publication Date
- 2026-08-27
Abstract
Description
FIELD OF THE INVENTION
[0001] The present invention relates to the field of compositions (especially prebiotic compositions), uses of the compositions, methods of using the compositions and methods of preparing the compositions. However, it will be appreciated that the invention is not limited to these particular fields of use. BACKGROUND OF THE INVENTION
[0002] The following discussion of the prior art is provided to place the invention in an appropriate technical context and enable the advantages of it to be more fully understood. It should be appreciated, however, that any discussion of the prior art throughout the specification should not be considered as an express or implied admission that such prior art is widely known or forms part of the common general knowledge in the field.
[0003] Patients receiving medical treatments, such as chemotherapy, immunotherapy and antibiotic treatments, often experience a decline in gastrointestinal microbiome diversity, and low diversity is associated with a greater incidence or likelihood of infections and other poor outcomes. For patients receiving such treatments there can also be an overgrowth of pathogenic species in the gastrointestinal tract. For example, in patients having haematological cancer treatment, such as allogeneic stem cell transplantation, the gastrointestinal microbiome composition has been strongly linked with patient outcomes, and increased complications such as infections, graft versus host disease (GVHD) and mortality are seen with less diversity. These complications have also been associated with a decline in short chain fatty acid levels in stool and serum, for example, as seen post-stem cell transplantation.
[0004] For example, during initial induction chemotherapy for acute leukemia there is an adverse shift in microbial composition, including a decrease in abundance of Faecalibacterium, Bacteroides and Bifidobacterium species and increased Escherichia coli and Enterococcus. Additionally, stool short chain fatty acid levels and plasma citrulline decrease. Citrulline is a marker of gut cell (enterocyte) mass, with lower levels indicating intestinal dysfunction and gastrointestinal toxicity.
[0005] A decrease in short chain fatty acid levels in the stool and serum is significant, as short chain fatty acids (such as butyrate, propionate and acetate) in the gastrointestinal tract are produced 2025200873 07 Feb 2025 through bacterial fermentation of fibre. If populations of certain bacterial species in the gastrointestinal tract decrease, then this can impact the production of short chain fatty acids. Such short chain fatty acids assist in maintenance of the gastrointestinal barrier, have an antiinflammatory and immunomodulating effect, and assist in suppressing the growth of pathogens. Maintaining gastrointestinal barrier function is important during cancer treatment, for example, as intestinal permeability increases post chemotherapy which has been linked with the development of bloodstream infections. Short chain fatty acids may also positively impact immune cell function. Lower short chain fatty acid levels have also been associated with more complications post stem cell transplantation including graft versus host disease and viral respiratory tract infections. The benefits of higher butyrate levels have been explored in patients undergoing treatment for other cancers, and in patients undergoing immunotherapy those who responded to treatment had a higher serum butyrate than non-responders (He et al. (2021)). Maintaining higher short chain fatty acid levels (such as butyrate), for example, is therefore likely to be very beneficial for many types of patients.
[0006] Dietary fibre positively impacts the gastrointestinal microbiome and influences microbial composition and short chain fatty acid production. A diverse high fibre diet is associated with higher microbial diversity. For example, the beneficial role of dietary fibre for colon cancer prevention and reducing the risk of chronic disease has been reported, however the literature on fibre intake during cancer treatment is limited. However, during immunotherapy treatment it was found that a greater dietary fibre intake (>20 g / day) was associated with higher progression free survival, compared to lower fibre intake (<20 g / day) (Spencer et al. (2021)). Similarly, in patients undergoing surgery for colorectal cancer, prebiotic fibre supplementation mitigated the decline in microbial diversity that occurred post operatively in the control group (Xie et al. (2019)). Nonetheless low oral fibre intake is common during cancer treatment due to the side effects of chemotherapy. SUMMARY OF THE INVENTION
[0007] In one aspect, the present invention advantageously overcomes or ameliorates one or more the disadvantages of the prior art, or at least to provide a useful alternative.
[0008] In another aspect, the present invention advantageously provides a composition and uses of that composition which enable improved consumption of increased amounts of dietary fibre. 2025200873 07 Feb 2025
[0009] According to a first aspect, the present invention provides a method of increasing fibre consumption in a subject in need thereof, comprising administering to the subject a composition comprising a fructan, a resistant starch and psyllium.
[00010] According to a second aspect, the present invention provides a method of: (i) promoting growth of short chain fatty acid producing bacteria in the gastrointestinal tract of a subject in need thereof; (ii) increasing short chain fatty acid production in the gastrointestinal tract of a subject in need thereof; and / or (iii) reducing the potential side effects associated with the consumption of fibre by a subject in need thereof; comprising administering to the subject a composition comprising a fructan, a resistant starch and psyllium.
[00011] In some embodiments, the inventors have found that the combination of a fructan (such as inulin), resistant starch and psyllium provides various advantages. Fructans such as inulin are rapidly fermented in the proximal colon, and both inulin and resistant starch support production of butyrate, a key short chain fatty acid that assists in maintaining gastrointestinal barrier integrity. Without wishing to be bound by theory, it is believed that the combination of a fructan and resistant starch may offer additional benefit compared to administration of a single fibre type, especially as there can be inter-individual variability in response to different fibres, and different fibre types exhibit different functional effects. However, at higher dosages of a fructan and a resistant starch, abdominal bloating and cramping can occur. The inventors have surprisingly found that psyllium, when combined with a fructan and resistant starch, can reduce such cramping and bloating as psyllium may assist fermentation to occur more slowly. Without wishing to be bound by theory, the inventors believe that psyllium can reduce colonic gas production, enable higher doses of a fructan and a resistant starch to be comfortably administered, and improve short chain fatty acid production across the colon.
[00012] In one embodiment of the second aspect, the method increases the consumption of fibre by the subject. The method may increase the fibre consumption by the subject by at least 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 200%, 250%, or 300% of the initial amount. The initial amount may be the amount of fibre consumption before the composition is administered for the first time. The method may result in the subject receiving a total amount of fibre of greater than 20 g / day, especially greater than 25 g / day, greater than 30 g / day, greater than 35 g / day or greater than 40 g / day. The method may result in the subject receiving a total amount 2025200873 07 Feb 2025 of fermentable fibre of greater than 10 g / day, or greater than 13 g / day, or greater than 15 g / day, or greater than 20 g / day, or greater than 25 g / day.
[00013] In one embodiment of the second aspect, the method reduces the potential side effects associated with the consumption of fibre by the subject. In one embodiment, the method reduces the side effects associated with the consumption of fibre by the subject. Side effects and potential side effects associated with consumption of fibre may include, for example, at least one of abdominal bloating and abdominal cramping.
[00014] In another embodiment of the method of the second aspect, the present invention provides a method of promoting growth (or abundance) of short chain fatty acid producing bacteria in the gastrointestinal tract of a subject in need thereof, comprising administering to the subject a composition comprising a fructan, a resistant starch and psyllium. The short chain fatty acid may be as described in the preceding paragraph. In one embodiment, the short chain fatty acid producing bacteria may be one or more selected from the group consisting of: Eubacterium species, Faecalibacterium species, Bifidobacterium species, Anaerostipes species, Roseburia species, Ruminococcus species and Anaerostipes species. The short chain fatty acid producing bacteria may be one or more selected from the group consisting of: Eubacterium rectale, Eubacterium hallii, Faecalibacterium prausnitzii, Bifidobacterium species, Anaerostipes species, Roseburia species, Anaerostipes caccae, and Anaerostipes hadrus. The initial amount may be the amount before the composition is administered for the first time. The growth of short chain fatty acid producing bacteria may be assessed using a technique such as shotgun metagenomic sequencing or 16s RNA sequencing. Such techniques are discussed in Galloway-Pena and Hanson (2021).
[00015] In one embodiment of the method of the second aspect, the present invention provides a method of increasing short chain fatty acid production in the gastrointestinal tract of a subject in need thereof, comprising administering to the subject a composition comprising a fructan, a resistant starch and psyllium. Exemplary short chain fatty acids may be of the formula C1-6alkyl-CO2H or C1-6alkyl-CO2-; especially C1-4alkyl-CO2H or C1-4alkyl-CO2-. Short chain fatty acids may be selected from one or more of the group consisting of butyrate, propionate and acetate (or butyric acid, propionic acid and acetic acid). As used herein, the term “short chain fatty acids” also encompasses their carboxylates. The increase of short chain fatty acid production may be assessed by measuring a change in the concentration of short chain fatty acids (such as butyrate) in either the stool or in blood (serum). The amount of short chain fatty acids in the gastrointestinal tract may be assessed using liquid chromatography mass spectrometry (for example as discussed in 4 2025200873 07 Feb 2025 Weng et al. (2024)). The initial concentration may be the concentration before the composition is administered for the first time.
[00016] Features of the methods of the first and second aspects may be as discussed below.
[00017] In one embodiment, the subject has cancer. In one embodiment, the subject has received or is receiving chemotherapy, immunotherapy and / or an antibiotic. In one embodiment, the subject has received chemotherapy, immunotherapy and / or an antibiotic. In another embodiment, the subject is receiving chemotherapy, immunotherapy and / or an antibiotic. The subject may be receiving a chemotherapy or an immunotherapy for a haematological cancer.
[00018] In one embodiment, the chemotherapy and / or the immunotherapy is to treat, or the cancer is: a solid cancer (or tumour) or a haematological cancer. The haematological cancer may be, for example, lymphoma, myeloma or leukemia. The leukaemia may be acute or chronic leukaemia, especially acute leaukaemia. The lymphoma may be non-Hodgkin’s lymphoma (either high or low grade). The lymphoma may be Hodgkin’s lymphoma. The subject may have a haematological cancer and be receiving or have received a stem cell transplant (including an allogeneic stem cell transplant). The solid cancer may be, for example, selected from the group consisting of: melanoma, a cancer of the gastrointestinal tract (including colorectal cancer, colon cancer, oesophageal cancer, gastric cancer or rectal cancer), breast cancer, prostate cancer, liver cancer, lung cancer, head and neck cancer, skin cancer, renal cancer, pancreatic cancer, bile duct cancer, urothelial cancer, bladder cancer, sarcoma, uterine cancer, endometrial cancer, ovarian cancer, cervical cancer, bone cancer and brain cancer. In one embodiment, the subject is receiving Chimeric Antigen Receptor T cell (Car T) Therapy.
[00019] In one embodiment, the subject is receiving enteral nutrition. The enteral nutrition may be provided to the subject following a stem cell transplant (for example if the subject has a haematological cancer). The enteral nutrition may be provided for 1-5 weeks following a stem cell transplant, including 2-4 weeks or 2-3 weeks. The enteral nutrition may comprise a fibre, especially a prebiotic fibre. The fibre may comprise one or more of inulin and resistant starch. The fibre may comprise one or more of: a polysaccharide and a gelling agent. The polysaccharide may be one or more of (especially two or more of, or three or more of, or four or more of, or five or more of) the group consisting of: inulin, resistant starch, oligofructose, soy polysaccharides and cellulose; especially at least inulin and resistant starch. In one embodiment, the gelling agent is arabic gum. 2025200873 07 Feb 2025
[00020] The enteral nutrition may be in any suitable amount. In one embodiment, the subject is receiving at least 5, 10, 15 or 20 g of enteral nutrition per day. In another embodiment, the subject is receiving at least 5, 10, 15 or 20 g of fibre by enteral nutrition per day. In one embodiment, the subject is receiving from 8-35 g, or from 10-28 g of fibre by enteral nutrition per day.
[00021] The composition may be administered at any suitable number of times per day. In one embodiment, the composition is administered at least once per day. In another embodiment, the composition is administered at least twice per day. In a further embodiment, the composition is administered at least three, four, five, or six times per day. In one embodiment, the composition is administered 1-3 times per day, or 1-2 times per day. In one embodiment, the composition is administered once per day. In another embodiment, the composition is administered twice per day. In one embodiment, the composition is administered once per day for the first two to three days, then then the composition is administered twice per day thereafter. When the composition is administered two or more times per day it may be administered at least 4 hours apart, especially at least 6, 7, 8 or 9 hours apart. When the composition is administered twice per day it may be administered in the morning and the evening.
[00022] The composition may be administered in a fluid. The fluid may be at a temperature below 40 °C, or below 35 °C. In one embodiment, the fluid is at a temperature at or below room temperature. The fluid may be any suitable beverage, including water. The fluid may be in any suitable amount. In one embodiment, the composition is administered in from 100-500 mL fluid, especially from 150 - 300 mL fluid, or about 250 mL fluid. The composition may be administered in a food. The food may be, for example, custard, yoghurt, cereal or ice cream. The fluid or food may be at a pH of from 4.5-9, especially at about pH 7.
[00023] The composition may be in any suitable form. In one embodiment, the composition is in solid form, especially in the form of a powder. When the composition is in powder form, it should be stirred well in a fluid before administration.
[00024] The composition may be administered orally. The composition may be administered with food.
[00025] In one embodiment, the composition is a prebiotic composition. A prebiotic is a substance that stimulates the growth of health promoting bacteria, and may be selectively utilized by host microorganisms to promote a health benefit. Prebiotics may comprise a specific type of fibre (for example, inulin or fructans, and galacto-oligosaccharides). While fructans (and inulin) 6 2025200873 07 Feb 2025 are typically regarded to be a prebiotic, there is less evidence for resistant starch (but resistant starch may be considered to be a candidate prebiotic).
[00026] In one embodiment, the only source of fibres in the composition is a fructan, a resistant starch and psyllium. In one embodiment, the only source of fermentable fibres in the composition is a fructan and a resistant starch. In one embodiment, the only source of non-fermentable fibre in the composition is psyllium.
[00027] In one embodiment, the composition consists essentially of a fructan, a resistant starch and psyllium. In another embodiment, the composition consists of a fructan, a resistant starch and psyllium.
[00028] The fructan may include linear chains of fructosyl groups. The fructan may optionally terminate in a glucosyl group. The fructan may comprise, consist essentially of or consist of one or more fructose groups and optionally a terminal glucose group. The fructan may be a fructosugar, a fructooligosaccharide or oligofructose. A fructan may comprise 3(1,2) linked fructose units, 3(2,6) linked fructose units, or a mixture of 3(2,6) linked fructose units with 3(1,2) branches. An exemplary fructan with 3(1,2) linked fructose units is inulin. An exemplary fructan with 3(2,6) linked fructose units is levan. An exemplary fructan with a mixture of 3(2,6) linked fructose units with 3(1,2) branches is gramminan. In one embodiment, the fructan comprises 3(1,2) linked fructose units.
[00029] Fructans may vary depending on their average fructosyl chain length, or the average number of repeating fructose units (this is the “degree of polymerization”). The fructan may have a degree of polymerization of greater than 2, greater than 5, greater than 8 or greater than 10. The fructan may have a degree of polymerization of from 2-20 or 1-10 (such as a fructosugar, a fructooligosaccharide or oligofructose). The fructan may have a degree of polymerization of from 2100, or from 2-60 or > 10. In one embodiment, the fructan comprises 3(1,2) linked fructose units and has a degree of polymerization of from 2-100, or from 2-60 or > 10; especially > 10. Typically, fructans comprising 3(1,2) linked fructose units (which may also be described as “inulin type fructans”) with a shorter degree of polymerization (for example less than 10) are fermented more rapidly by bacteria, whereas longer-chain fructans (such as inulin) are fermented more slowly. Inulin, for example, typically ferments in the proximal colon.
[00030] The composition may comprise one or more types of fructan. In one embodiment, the composition comprises 1, 2 or 3 types of fructan. In another embodiment, the composition comprises 1 or 2 types of fructan, or 1 type of fructan. 2025200873 07 Feb 2025
[00031] The fructan may be in any suitable form. In one embodiment, the fructan is a solid. The fructan may be a powder.
[00032] The fructan may be prepared from any suitable source. In one embodiment, the fructan (such as inulin) is prepared from at least one of the following: chicory roots, wheat, onion, banana, garlic, and leek; especially chicory roots. Inulin supplementation may lead to increased abundances of short chain fatty acid producing bacteria.
[00033] The amount of fructan administered in the composition may be less than 10 g / day, or less than 9 g / day, or less than 8 g / day, or less than 7.8 g / day, or less than 7.6 g / day, or less than 7.4 g / day or less than 7.2 g / day. The amount of fructan administered in the composition may be from 1-10 g / day, especially from 2-10 g / day, or from 1-8 g / day, or from 2-8 g / day or from 3-8 g / day, or from 4-8 g / day, or from 5-8 g / day, or from 6-7.5 g / day, or from 6.5 - 7.5 g / day or about 7 g / day. The composition may comprise from 12-35 wt% fructan, or from 15-32 wt% fructan, or from 17-30 wt% fructan, or from 18-29 wt% fructan, or from 19-28 wt% fructan, or from 20-27 wt% fructan, or from 21-26 wt% fructan, or about 23 wt% fructan. In these embodiments, the fructan may be a fructan comprising [3(1,2) linked fructose units, such as inulin.
[00034] The term “resistant starch” is known in the art and refers to dietary starch that resists digestion in the small intestine. Resistant starch is typically fermented in the large intestine. Resistant starch may be fermented by bacteria in the colon and produce short chain fatty acids (as discussed above). The resistant starch may be selected from one or more of the group consisting of: type 1, type 2, type 3, type 4 or type 5. Type 1 may be physically protected starch. Type 1 may be found in whole or partially milled grains and seeds, legumes. Type 2 may be ungelatinized resistant granules with type B crystallinity, slowly hydrolysed by a-amylase. Type 2 may be found in raw potatoes, green bananas, some legume and high-amylose corn. Type 3 may be retrograded starch. Type 3 may be found in cooked and cooled potatoes, bread, cornflakes and food products with repeated moist heat treatment. Type 4 may be chemically modified starches due to crosslinking with chemical reagents. Type 4 may be found in foods in which modified starches have been used (for example in breads and cakes). Type 5 may be amylose-lipid complexes. Type 5 may be found in foods with high amylose content. Resistant starches are further discussed in Raigond et al. (2015). In one embodiment, the resistant starch is type 2 or type 4 resistant starch, especially a type 2 resistant starch. Resistant starch may increase short chain fatty acid production in the gastrointestinal tract of a subject, and promote growth of short chain fatty acid producing bacteria in the gastrointestinal tract of a subject. 2025200873 07 Feb 2025
[00035] The composition may comprise one or more types of resistant starch. In one embodiment, the composition comprises 1, 2 or 3 types of resistant starch. In another embodiment, the composition comprises 1 or 2 types of resistant starch, or 1 type of resistant starch.
[00036] The resistant starch may be derived from any suitable source. In one embodiment, the resistant starch is potato or maize resistant starch, especially potato resistant starch. Both potato and maize resistant starch are a type 2 resistant starch.
[00037] The amount of resistant starch administered in the composition may be less than 22 g / day, or less than 20 g / day, or less than 18 g / day, or less than 16 g / day, or less than 14 g / day, or less than 12 g / day or less than 11 g / day. The amount of resistant starch administered in the composition may be from 1-22 g / day, especially from 2-20 g / day, or from 1-18 g / day, or from 218 g / day or from 4-18 g / day, or from 5-18 g / day, or from 6-18 g / day, or from 7-17 g / day, or from 9 - 17 g / day, or from 12-20 g / day, or from 13-19 g / day, or from 14-18 g / day, or from 15-17 g / day, or about 16 g / day, or from 6-14 g / day, or from 7-13 g / day, or from 8-12 g / day, or from 9-11 g / day, or about 10g / day. The composition may comprise from 20-75 wt% resistant starch, or from 2060 wt% resistant starch, or from 25-55 wt% resistant starch, or from 20-45 wt% resistant starch, or from 25-40 wt% resistant starch, or from 30-35 wt% resistant starch, or about 32-33 wt% resistant starch, or from 35-65 wt% resistant starch, or from 40-60 wt% resistant starch, or from 45-60 wt% resistant starch, or about 52 wt% resistant starch. In these embodiments, the resistant starch may be potato or maize resistant starch.
[00038] The amount of fermentable fibres (or the amount of fructan and resistant starch) administered in the composition may be more than 10 g / day, or more than 12 g / day, or more than 14 g / day, or more than 15 g / day. The amount of fermentable fibres administered in the composition may be less than 30 g / day, or less than 25 g / day, or less than 20 g / day, or less than 18 g / day. The amount of fermentable fibres administered in the composition may be from 2-30 g / day, especially from 5-30 g / day, or from 10-30 g / day, or from 15-30 g / day, or from 20-30 g / day, or from 22-26 g / day, or from 12-22 g / day, or from 14-20 g / day or from 16-18 g / day. The composition may comprise from 40-90 wt% fermentable fibres (or fructan and resistant starch), or from 45-80 wt% fermentable fibres, or from 50-60 wt% fermentable fibres, or about 55 wt% fermentable fibres, or from 55-85 wt% fermentable fibres, or from 60-85 wt% fermentable fibres, or from 65-85 wt% fermentable fibres, or from 70-85 wt% fermentable fibres, or from 75 - 80 wt% fermentable fibres. 2025200873 07 Feb 2025
[00039] The psyllium may be in any suitable form. The psyllium may be in the form of psyllium husks or psyllium powder, especially psyllium husks. The psyllium powder may be in the form of ground husks. The psyllium powder may have a particle size of less than about 1 mm in diameter.
[00040] The amount of psyllium administered in the composition may be more than 2 g / day, or more than 3 g / day, or more than 4 g / day, or more than 5 g / day. The amount of psyllium administered in the composition may be less than 15 g / day, or less than 10 g / day, or less than 9 g / day, or less than 8 g / day. The amount of psyllium administered in the composition may be from 1-15 g / day, especially from 2-10 g / day, or from 3-9 g / day, or from 4-8 g / day or from 4-6 g / day, or from 5-9 g / day, or from 6-8 g / day, or about 5 g / day, or about 6 g / day, or about 7g / day. The composition may comprise from 5-40 wt% psyllium, or from 10-30 wt% psyllium, or from 10-25 wt% psyllium, or from 10-23 wt% psyllium, or from 13-30 wt% psyllium, or from 14-25 wt% psyllium, or from 15-23 wt% psyllium, or from 16-22 wt% psyllium, or from 17-21 wt% psyllium, or about 19 wt% psyllium, or from 12-19 wt% psyllium, or from 15-17 wt% psyllium, or about 16 wt% psyllium, or from 15-35 wt% psyllium, or from 18-30 wt% psyllium, or from 20-25 wt% psyllium, or from 21-24 wt% psyllium, or about 22 wt% psyllium.
[00041] In one embodiment, the subject is administered from 2-10 g / day fructan (such as inulin); from 2-22 g / day resistant starch; and from 2-10 g / day psyllium.
[00042] In one embodiment, the ratio (by weight) of psyllium : resistant starch and fructan in the composition is from 1:2 to 1:6, or from 1:2 to 1:5, or from 1:2.5 to 1:4.5, or from 1:3 to 1:4, or about 1:3.4. In one embodiment, the ratio (by weight) of psyllium to resistant starch is from 1:1 to 1:4, or from 1:1.2 to 1:3, or from 1:1.5 to 1:2.5, or about 1:2. In one embodiment, the ratio (by weight) of psyllium to fructan is from 1:1 to 1:2, or from 1:1.1 to 1:1.8, or from 1:1.2 to 1:1.6, or about 1:1.4. In one embodiment, the ratio of fructan to resistant starch is from 1:0.5 to 1:3, or from 1:1 to 1:2, or from 1:1.1 to 1:1.8, or from 1:1.2 to 1:1.6, or about 1:1.4.
[00043] In one embodiment, the composition comprises from 20-60 wt% resistant starch; from 15-32 wt% fructan (such an inulin); and from 10-30 wt% psyllium.
[00044] The combination of a fructan, which typically ferments in the proximal colon, and a resistant starch, which typically ferments in the more distal colon, is likely to enable fermentation across the entire colon rather than only in a small part. Without wishing to be bound by theory, the inventors believe that this would promote tolerance of the composition when administered to a subject, and also support gastrointestinal barrier function due to short chain fatty acid production across the colon (which in turn may improve gastrointestinal barrier function over a greater area 10 2025200873 07 Feb 2025 of the colon). The combination may also support production of butyrate in the gastrointestinal tract, and can also increase stool and serum short chain fatty acid levels compared to a low fibre diet. Without wishing to be bound by theory, the inventors believe that administration of psyllium to the subject slows colonic transit time and the rate of fermentation of the fructan and the resistant starch, reducing bloating and cramping and improving patient tolerance.
[00045] In one embodiment the composition may comprise a carrier or excipient. The carrier or excipient may be selected from one or more of the group consisting of: colourants, flavouring agents, sweetening agents, dispersants and the like. In one embodiment, the composition comprises no carriers or excipients.
[00046] In some embodiments, the composition of the first or second aspect may be the composition of the seventh aspect.
[00047] According to a third aspect, the present invention provides a use of a fructan, a resistant starch and psyllium in the manufacture of a medicament for increasing fibre consumption in a subject in need thereof. The medicament of the third aspect may be the composition as defined in the first or second aspects, or the composition of the seventh aspect.
[00048] According to a fourth aspect, the present invention provides a use of a fructan, a resistant starch and psyllium in the manufacture of a medicament for: (i) promoting growth of short chain fatty acid producing bacteria in the gastrointestinal tract of a subject in need thereof; (ii) increasing short chain fatty acid production in the gastrointestinal tract of a subject in need thereof; and / or (iii) reducing the potential side effects associated with the consumption of fibre by a subject in need thereof. The medicament of the fourth aspect may be the composition as defined in the first or second aspects, or the composition of the seventh aspect.
[00049] According to a fifth aspect, the present invention provides a composition comprising a fructan, a resistant starch and psyllium for increasing fibre consumption in a subject in need thereof. The composition in the fifth aspect may be the composition as defined in the first or second aspects, or the composition of the seventh aspect.
[00050] According to a sixth aspect, the present invention provides a composition comprising a fructan, a resistant starch and psyllium for: (i) promoting growth of short chain fatty acid producing bacteria in the gastrointestinal tract of a subject in need thereof; (ii) increasing short chain fatty acid production in the gastrointestinal tract of a subject in need thereof; and / or (iii) reducing the potential side effects associated with the consumption of fibre by a subject in need 2025200873 07 Feb 2025 thereof. The composition in the sixth aspect may be the composition as defined in the first or second aspects, or the composition of the seventh aspect.
[00051] Features of the third and fifth aspects of the invention may be as described for the first aspect. Features of the fourth and sixth aspects of the invention may be as described for the second aspect.
[00052] According to a seventh aspect, the present invention provides a composition comprising a fructan, a resistant starch and psyllium. Features of the seventh aspect of the invention may be as described for the first to sixth aspects of the invention. In particular, the composition of the seventh aspect may be the composition as defined in the first to sixth aspects of the present invention.
[00053] In one embodiment of the seventh aspect, the fructan is inulin. In one embodiment, the composition comprises from 45-80 wt% of fructan and resistant starch. In one embodiment, the composition comprises from 13-30 wt% psyllium. In one embodiment, the composition comprises from 20-60 wt% resistant starch, from 15-32 wt% inulin and from 10-30 wt% psyllium.
[00054] According to an eighth aspect, the present invention provides a method of preparing the composition of the seventh aspect. The method may comprise the step of mixing a fructan, a resistant starch and psyllium. Features of the eighth aspect may be as described for the first to seventh aspects of the present invention.
[00055] The skilled addressee will understand that the invention comprises the embodiments and features disclosed herein as well as all combinations and / or permutations of the disclosed embodiments and features. DEFINITIONS
[00056] In describing and claiming the present invention, the following terminology will be used in accordance with the definitions set out below. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments of the invention only and is not intended to be limiting.
[00057] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one having ordinary skill in the art to which the invention pertains. 2025200873 07 Feb 2025
[00058] Unless the context clearly requires otherwise, throughout the description and the claims, the terms “comprise”, “'comprising”, and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”. For example, a composition, mixture, process or method that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process or method.
[00059] The transitional phrase "consisting of” excludes any element, step, or ingredient not specified. If in the claim, such would close the claim to the inclusion of materials other than those recited except for impurities ordinarily associated therewith. When the phrase "consisting of" appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole.
[00060] The transitional phrase "consisting essentially of" is used to define a composition, process or method that includes materials, steps, features, components, or elements, in addition to those literally disclosed, provided that these additional materials, steps, features, components, or elements do not materially affect the basic and novel characteristic(s) of the claimed invention. The term "consisting essentially of" occupies a middle ground between "comprising" and "consisting of".
[00061] Where the applicant has defined an invention or a portion thereof with an open-ended term such as "comprising", it should be readily understood that (unless otherwise stated) the description should be interpreted to also describe such an invention using the terms ''consisting essentially of" or "consisting of." In other words, with respect to the terms “comprising”, “consisting of”, and “consisting essentially of”, where one of these three terms is used herein, the presently disclosed and claimed subject matter may include the use of either of the other two terms. Thus, in some embodiments not otherwise explicitly recited, any instance of “comprising” may be replaced by “consisting of” or, alternatively, by “consisting essentially of”.
[00062] While reference may be made in this disclosure to the invention comprising a combination of a plurality of elements, it is also understood that this invention is regarded to comprise combinations which omit or exclude one or more of such elements, even if this omission or exclusion of an element or elements is not expressly stated herein, unless it is expressly stated herein that an element is essential to the applicant's combination and cannot be omitted. It is further understood that the related prior art may include elements from which this invention may be distinguished by negative claim limitations, even without any express statement of such negative 2025200873 07 Feb 2025 limitations herein. It is to be understood, between the positive statements of applicant's invention expressly stated herein, and the prior art and knowledge of the prior art by those of ordinary skill which is incorporated herein even if not expressly reproduced here for reasons of economy, that any and all such negative claim limitations supported by the prior art are also considered to be within the scope of this disclosure and its associated claims, even absent any express statement herein about any particular negative claim limitations.
[00063] As used herein, with reference to numbers in a range of numerals, the terms "about," "approximately" and "substantially" are understood to refer to the range of -10% to +10% of the referenced number, preferably -5% to +5% of the referenced number, more preferably -1 % to + 1 % of the referenced number, most preferably -0 .1 % to +0 .1 % of the referenced number. Moreover, with reference to numerical ranges, these terms should be construed as providing support for a claim directed to any number or subset of numbers in that range. For example, a disclosure of from 1 to 10 should be construed as supporting a range of from 1 to 8, from 3 to 7, from 1 to 9, from 3.6 to 4.6, from 3.5 to 9.9, from 8 to 10, and so forth.
[00064] The terms “preferred” and “preferably” refer to embodiments of the invention that may afford certain benefits, under certain circumstances. However, other embodiments may also be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful, and is not intended to exclude other embodiments from the scope of the invention.
[00065] The complete disclosures of the patents, patent documents and publications cited herein are incorporated by reference in their entirety as if each were individually incorporated.
[00066] Unless expressly stated to the contrary, "or" refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).
[00067] The term "and / or" used in the context of "X and / or Y" should be interpreted as "X," or "Y," or "X and Y." Similarly, "at least one of X or Y" should be interpreted as "X," or "Y," or "both X and Y."
[00068] The indefinite articles "a" and "an" preceding an element or component of the invention are intended to be non-restrictive regarding the number of instances (i.e., occurrences) of the element or component. Therefore "a" or "an" should be read to include one or at least one, and the 2025200873 07 Feb 2025 singular word form of the element or component also includes the plural unless the number is obviously meant to be singular.
[00069] As used herein, wt.% refers to the weight of a particular component relative to total weight of the referenced composition.
[00070] The term “alkyl” refers to a straight-chain or branched alkyl substituent containing the specified number of carbon atoms. Examples of suitable alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl and the like. The number of carbons referred to relates to the carbon backbone and carbon branching.
[00071] Various features of the embodiments of the invention disclosed herein are, for brevity, described in the context of a single embodiment, but may also be provided separately or in any suitable sub-combination. All combinations of the embodiments are specifically embraced by the illustrative embodiments disclosed herein just as if each and every combination was individually and explicitly disclosed. In addition, all sub-combinations listed in the embodiments describing such variables are also specifically embraced by the present compositions and are disclosed herein just as if each and every such sub-combination was individually and explicitly disclosed herein.
[00072] In the foregoing paragraphs, where various ratios of components have been disclosed. It will be appreciated that these ratios of components can be combined in any disclosed combination. EXAMPLES
[00073] The present invention will now be described with reference to the following examples which should be considered in all respects as illustrative and non-restrictive. The aspects described above, as well as other apparent aspects, advantages, and objectives of the present invention are apparent from the examples below. Materials
[00074] In the compositions discussed below, the inulin product used is Orafti™ GR. The resistant potato starch product was Solnul™ resistant potato starch. The psyllium product was Psyllium Husk 95% pure U.S.P. / EP.
[00075] Further details of these products follow: 2025200873 07 Feb 2025 - Orafti™ GR was manufactured by Beneo in Belgium or Chile and sold in Australia through Invita Australia. Orafti™ GR consists mainly of inulin derived from chicory and it is a granulated powder. Inulin includes oligo- and polysaccharides composed of fructose units linked together by P-(2,1 )-linkages. Almost every fructose chain is terminated by a glucose unit. The number of fructose and glucose units in inulin (Degree of Polymerization = DP) ranges mainly between 2 and 60. Orafti™ GR has an average DP of > 10. It is a fine, white to slightly yellow powder, with a solubility in water of approximately 120 g / L at 25 °C, and approximately 350 g / L at 90 °C. It has a bulk density of 620 g / L ± 50 g / L. Orafti™ GR includes at least 90 g / 100 g dry matter of inulin (as measured by AOAC997.08), and a maximum of 10 g / 100 g dry matter of glucose, fructose and sucrose (as measured by AOAC997.08). It has a dry matter of 97 ± 2 g / 100 g (as measured by vacuum, <35 mbar, 70 °C, 20h) and a pH of 6 ± 1. It has a dietary fiber content (non-digestible carbohydrate oligo- or polymers with three or more monomeric units (DP > 3); excludes inulobiose) of 89 g / 100 g (as measured by AOAC 997.08). - Solnul™ resistant potato starch was manufactured by Solnul™ in Canada and sold in Australia by Ingredients Plus. Specifications: item number SOL100, 100% Resistant Potato Starch (Solanum tuberosum), used parts: tuber. Free-flowing white powder with neutral taste and smooth mouthfeel. < 20% moisture (assessed by method SOP-050-06; AOAC 930.15. 18.5g moisture / 100g product - AOAC 950.46B), pH 6.0-8.0 (assessed by method SOP-050-07; CRA B-44-1); Total carbohydrate > 80% (81.1 g / 100g product); Resistant Starch: > 60% ‘as is’ basis (assessed by method SOP-050-20; AOAC2002.02. 61.7 g / 100 g of product - AOAC2002.02); Total Dietary Fiber:> 63% ‘as is’ basis (AOAC 2009.01. 67.1 g / 100 g product - AOAC2009.01). - Psyllium Husk 95% pure U.S.P. / EP was manufactured in India and packaged and sold in Australia by Bonvit™. The product is a pale buff coloured to off white coloured whole husk, not marked odour. Moisture / Loss Drying was 8.80%. Total consumable fiber was 85.05%.
[00076] For the clinical trials, the three powdered products were combined and repackaged into sealed individual serve sachets by Pakco in Victoria, Australia. The individual sachets were stored at room temperature and provided to the trial participants every one to four weeks. For sachets for Prebiotic Composition 2, each sachet contained 3.5 g psyllium product, 8 g resistant potato starch and 4 g inulin. Example 1: Prebiotic Composition 1 2025200873 07 Feb 2025
[00077] A prebiotic composition was prepared containing 3.5 g psyllium product, 8 g resistant potato starch and 5 g inulin. The composition was to be administered twice per day, so the total amount to be administered per day was 7 g psyllium product, 16 g resistant potato starch and 10 g inulin. The composition was in the form of a powder. Example 2: Prebiotic Composition 2
[00078] A prebiotic composition was prepared containing 3.5 g psyllium product, 8 g resistant potato starch and 4 g inulin. The composition was to be administered twice per day, so the total amount to be administered per day was 7 g psyllium product, 16 g resistant potato starch and 8 g inulin. The composition was in the form of a powder. Example 3: Preliminary Study
[00079] Four healthy people, who were all on a full diet, trialled Prebiotic Composition 1 (Example 1) and Prebiotic Composition 2 (Example 2). The compositions were administered twice per day, once in the morning and once in the evening. Two of the healthy people tolerated both compositions with no gastrointestinal side effects. The remaining two healthy people reported some gastrointestinal side effects with Prebiotic Composition 1. All four people reported excellent tolerance of Prebiotic Composition 2.
[00080] Comparison Prebiotic Composition 2A was prepared, which contained 4 g inulin and 8 g resistant potato starch (but no psyllium product). Comparison Prebiotic Composition 2A was taken twice per day by a healthy person, so that the total daily amount administered was 8 g inulin and 16 g resistant potato starch per day. This person experienced significant abdominal cramping with this composition. Example 4: Clinical Trial - Treatment during allogeneic stem cell transplantation
[00081] Australian New Zealand Clinical Trial Registry No. ACTRN12624000262505.
[00082] A randomized controlled trial which studied the feasibility of an oral prebiotic fibre supplement during allogeneic haematopoietic stem cell transplantation is in progress. This trial evaluates the feasibility of oral plus enteral prebiotic fibre supplementation during allogeneic stem cell transplantation (SCT) and the impact on clinical outcomes, the microbiome and immune function. The trial is taking place in the haematology unit at the Royal Brisbane and Women's 2025200873 07 Feb 2025 Hospital. The trial compares oral and enteral supplementation (group 1) to standard care (group 2).
[00083] Group 1 is receiving an oral and enteral prebiotic supplement (Prebiotic Composition 2 Example 2). This intervention group is commencing an oral prebiotic fibre supplement from a week prior to the start of conditioning therapy and continued until a month post SCT (typically the composition would be provided for five to six weeks depending on the type of transplant conditioning). Prebiotic Composition 2 (Example 2) is administered in two sachets per day to provide a combined dose of 22g fibre per day (including 7 g from inulin, 5 g from psyllium and 10 g from resistant starch) in 31 g of composition. Participants are advised to take the supplement with a meal and to commence 1 sachet per day for the first 3 days then increase to 2 sachets per day. Participants are advised to: (i) add Prebiotic Composition 2 to 1 cup of cool or room temperature fluid in the morning and evening, stir well and drink immediately, or (ii) mix the composition into food of thicker consistency (e.g. custard, yoghurt, cereal or ice cream) but in this case a glass of water should be consumed at the same time. The composition should not be mixed with hot food or fluid or acidic liquids (pH <4.5), such as sports drinks, soft drinks and fruit juice. The intervention group commenced fibre containing enteral nutrition (EN) on day one post SCT and increased the feeding rate as per usual care. Participants on enteral nutrition receive a polymeric ready to hang formula (1.2 kcal / mL, 63 g protein and 15 g fibre per litre) containing inulin, oligofructose, arabic gum, soy polysaccharides, cellulose and resistant starch providing 10-28g fibre per day (depending on the feeding rate required). Participants are provided with high protein meals, snacks and drinks throughout their admission.
[00084] Participants receiving partial prebiotic enteral nutrition (at 30ml / hr or 50ml / hr) to meet part of their nutritional requirements were encouraged to continue 1 prebiotic fibre oral sachet per day. Participants receiving full rate prebiotic enteral nutrition (>50ml / hr) to meet full estimated nutritional requirements (due to consuming minimal or nil oral intake) could cease the oral prebiotic supplement. Enteral nutrition may be achieved via a 10-12 Fr nasogastric tube. Once enteral nutrition reduces to meet partial requirements the oral prebiotic supplement recommenced at 1 sachet per day. Once enteral nutrition ceases participants were encouraged to take 2 sachets per day until study cessation. Adherence to prebiotic fibre supplementation was measured by participants reporting the number of prebiotic fibre sachets consumed weekly (assessed at timepoints (1), (2), (3) and (4) outlined below). Additionally during provision of prebiotic enteral nutrition the amount provided were collected from fluid balance charts. 2025200873 07 Feb 2025
[00085] Group 2 is a control group which are receiving standard care. This group receives standard fibre free enteral nutrition from day one after transplant as per usual care. The feeding commencement time, rate and cessation are as per usual care (the same as group 1.). Participants in the control group receive a non-fibre enteral nutrition formula from day one post SCT as per usual care (following the RBWH ‘Allogeneic stem cell transplant nutrition support protocol’). This involves provision of a polymeric non-fibre ready to hang formula (1.2 kcal / mL, 63 g protein per litre, 0 g fibre per litre). The feeding rate increases if oral intake declines as per usual care described above. Tolerance of enteral nutrition in both the control and intervention group is monitored and if poor, participants are changed to parenteral nutrition as per standard care. Tolerance of enteral nutrition in both groups are monitored and if poor, participants are changed to parenteral nutrition (PN). Both enteral nutrition and parenteral nutrition cease once oral intake is >50% meals and two snacks or high protein drinks per day post neutrophil engraftment as per the unit nutrition protocol. During the inpatient stay patients are provided with high protein high energy meals, drinks and snacks.
[00086] Outcomes of the trial include (in addition to these, gastrointestinal microbiome diversity and composition (e.g. through stool sample collection at timepoints (0), (2) and (5), via shotgun metagenomic sequencing), serum and stool SCFA levels and citrulline analysis, and immune function (cytokines and T cell subsets) would be assessed - blood sample collection would be collected at at least timepoints (0), (2), (4) and (5)): Outcome Assessment method Timepoint Feasibility of prebiotic fibre supplementation, defined as consuming >80% of the prescribed supplement (oral + enteral) over the study period. Calculating the percent of goal prebiotic fibre sachets consumed over the trial period. When supplementation ends. Amount of prescribed enteral nutrition received Fluid balance charts Collected daily during provision of enteral nutrition Patient acceptability of the oral prebiotic supplement Self developed questionnaire At the end of conditioning treatment and at the end of supplementation Appetite PRO-CTCAE (Patient Reported Outcomes of the Common Terminology Criteria for Adverse Events) tool and CTCAE tool At baseline pre supplementation then weekly from the end of conditioning to 1 month post transplant at the end of supplementation Quality of life EORTC QLQ-C30 validated questionnaire At baseline and at the end of supplementation 2025200873 07 Feb 2025 Unplanned hospital admissions by 100 days post transplant Hospital medical chart Assessed at day 100 post transplant Duration of enteral nutrition Fluid balance charts Assessed at hospital discharge Requirement for parenteral nutrition Medical chart The number of participants who required parenteral nutrition will be assessed on hospital discharge Nutritional status Subjective global assessment (SGA) At baseline and at the end of supplementation Dietary intake Assessed using the Monash validated CNAQ tool (comprehensive nutrition assessment questionnaire - Barrett and Gibson 2010) at baseline as well as patients self reporting intake via a food diary for two days per week. CNAQ only at baseline. Intake via food diary collected at each timepoint- every one to two weeks from the end of conditioning to the end of supplementation. This is timepoints (0), (2), (3), (4) and (5) Length of hospital stay Medical chart At hospital discharge Incidence of infections CTCAE > grade 2 grading from medical charts Collected continuously from study commencement to 100 days post transplant Acute graft versus host disease Grade and site will be collected from medical charts Day 100 post transplant Disease status medical chart day 100 post transplant Survival medical chart Day 100 after transplant Nausea PRO-CTCAE tool and CTCAE tool At baseline pre supplementation then every one to two weeks from the end of conditioning to 1 month post transplant at the end of supplementation. This is timepoints (0), (2), (3), (4) and (5) Mucositis PRO-CTCAE tool and CTCAE tool At baseline pre supplementation then every one to two weeks from the end of conditioning to 1 month post transplant at the end of supplementation. This is timepoints (0), (2), (3), (4) and (5) Diarrhoea PRO-CTCAE tool and CTCAE tool At baseline pre supplementation then every one to two weeks from the end of 2025200873 07 Feb 2025 conditioning to 1 month post transplant at the end of supplementation. This is timepoints (0), (2), (3), (4) and (5)
[00087] Exploratory endpoints may include SCFA concentration in stool and serum; stool microbial diversity and composition, citrulline concentration, and immune markers (T cell subsets and inflammatory cytokines. Patients for the Trial - Age: age 18 years or older - Gender: Both males and females - Other inclusion criteria: o undergoing allogeneic myeloablative or reduced intensity myeloablative allogeneic stem cell transplantation at the Royal Brisbane and Women’s Hospital (RBWH) - Exclusion Criteria: o Healthy volunteer o inflammatory bowel disease o formal diagnosis of irritable bowel syndrome o gastrointestinal resection o ileostomy or colostomy o any bariatric surgery including gastric bypass surgery, sleeve gastrectomy and gastric band o any other contraindication to a high fibre diet (e.g. active diverticulitis or bowel obstruction) o allergy / intolerance to any ingredient in the fibre supplement or enteral feed o current and planned ongoing consumption of probiotic or prebiotic supplements o hepatitis B, hepatitis C or HIV infection unless viral load negative o participation in a GVHD prevention trial during SCT o on carbamazepine o inability to provide written informed consent
[00088] Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures): Yes, the investigator recruiting participants will be unable to see which group they 2025200873 07 Feb 2025 will be allocated to until after recruitment when the randomisation will be completed in RedCap (Research Electronic Data Capture). In RedCap future allocations are concealed.
[00089] Methods used to generate the sequence in which subjects will be randomised (sequence generation): Simple randomisation using a randomisation table created by computer software then entered into Redcap database by an investigator not involved in recruitment.
[00090] Masking / blinding: Open (masking not used)
[00091] Intervention assignment: Parallel
[00092] Phase: Phase 1 / Phase 2
[00093] Type of endpoint / s: Safety / efficacy
[00094] Target number of patients: 36 (24 in Group 1, 12 in Group 2)
[00095] Data collection timepoints: (0) baseline (at transplant workup / preconditioning), (1) 1 week pre conditioning (supplementation commencement), (2) post conditioning (pre EN), (3) 1 week post-transplant, (4) hospital discharge, (5) one month post SCT, (6) 100 days post SCT. Preliminary Results from Five Patients Fibre supplement tolerance:
[00096] At baseline, participants had a median fibre intake of 24g per day from their food intake. The goal supplement dose in the clinical trial is two fibre sachets per day while not receiving any additional nutrition support via enteral feeding (in this instance a fibre containing enteral feed is given and sachet doses are reduced or ceased depending on feeding rate). The goal supplement of two sachets per day provides 8g inulin, 16g resistant starch and 7g psyllium in a total of 31g supplement which provides 22g fibre.
[00097] Prior to transplant (prior to and during conditioning chemotherapy) median fibre supplement consumption was 80% of the goal amount (range 52-100%). In 4 weeks post stem cell transplantation a median 55% of the supplement goal was consumed (range 36-86%). The reduction in consumption of the supplement in this time period is consistent with previous data regarding the impact of transplantation on adequacy of oral intake (Andersen et al., (2015)). Supplement acceptability survey 2025200873 07 Feb 2025
[00098] All patients complete an acceptability survey of the supplement, six patients have completed this to date. Preliminary results from the survey completion after chemotherapy indicates: • All patients agreed the sachet size was a good amount to take at one time • 67% of patients felt the supplement was easy to take twice a day, 33% of patients did not agree or disagree with this statement. • 67% of patients reported no side effects to taking the supplement • 83% of patients reported they would continue to take the supplement in the future • No patients felt they needed to alter their diet when taking the supplement Example 5: Clinical Trial - Treatment in Acute Leukemia
[00099] Australian New Zealand Clinical Trial Registry No. ACTRN12624000792527. [000100] A randomized controlled trial which studies the feasibility of an oral prebiotic fibre supplement during treatment for acute leukemia is to be conducted. The study is a randomized control trial in patients with newly diagnosed acute leukemia and considered the impact of the fibre supplement on clinical outcomes, the microbiome and immune function. The trial is being performed at the Royal Brisbane and Women's Hospital. The trial compares oral prebiotic supplementation with Prebiotic Composition 2 (Example 2) (group 1) to standard care (group 2). [000101] Group 1 is to commence treatment with Prebiotic Composition 2 (Example 2) from the start of induction treatment after diagnosis and is to continue until the end of consolidation chemotherapy. The supplement is provided for 3-6 months depending on number of consolidation cycles required. Prebiotic Composition 2 (Example 2) is administered in two sachets per day to provide a combined dose of 22g fibre per day. Participants are advised to take the supplement with a meal and to commence 1 sachet per day for the first 3 days then increase to 2 sachets per day. Adherence is measured by patients reporting consumption fortnightly (number of sachets provided compared to number remaining each fortnight and whether full sachets were consumed). [000102] Group 2 is a control group which received standard care with no fibre supplementation. There is no difference in nutrition care or medical treatment between groups. 2025200873 07 Feb 2025 [000103] Outcomes of the trial include: Outcome Assessment method Timepoint Feasibility of prebiotic fibre supplementation, defined as patients consuming >80% of the prescribed supplement over the study period Patient report of number of sachets consumed compared to number provided fortnightly. This is collected in person during inpatient treatment and by a REDCap emailed questionnaire when an outpatient (specifically designed for this study). Every week during induction treatment then every two weeks during the remaining supplementation period. Patient acceptability of the oral prebiotic supplement A questionnaire developed specifically for the study sent from REDCap. At the end of induction treatment and at the end of second consolidation treatment. Incidence of infections Common Terminology Criteria for Adverse Events (CTCAE) > grade 2 grading from medical chart Collected continuously from study commencement to the end of the supplementation period. Length of hospital stay (days) medical chart At hospital discharge after induction treatment. Unplanned hospital admissions medical chart At the end of second consolidation treatment Disease relapse medical chart End of study (end of acute leukemia treatment for each patient, either end of consolidation treatment or post stem cell transplantation) Nutritional status Subjective global assessment tool Baseline, end of induction treatment and end of second consolidation treatment Dietary intake Assessed using the validated CNAQ tool (comprehensive nutrition assessment questionnaire) at baseline as well as patients self reporting intake via a 24 hour recall CNAQ at baseline only. 24 hour recalls at baseline, end of induction treatment, end of second consolidation treatment, and end of all consolidation (for patients having more than 2 cycles). Gastrointestinal symptoms CTCAE and PRO-CTCAE Baseline, weekly during induction treatment and end of second consolidation treatment Quality of life The European Organisation for Research and Treatment of Cancer, quality of life questionnaire (EORTC QLQ-C30) Baseline, end of induction treatment, end of second consolidation treatment. 2025200873 07 Feb 2025 Survival medical chart End of induction treatment, end of second consolidation and end of treatment for acute leukemia. Patients for the Trial - Age: age 18 years or older - Gender: Both males and females - Other inclusion criteria: o newly diagnosed acute leukemia or myelodysplasia undergoing high intensity intravenous induction chemotherapy at the Royal Brisbane and Women’s Hospital (RBWH) o ability to provide written informed consent - Exclusion Criteria o healthy volunteer o inflammatory bowel disease o formal diagnosis of irritable bowel syndrome o gastrointestinal resection o ileostomy or colostomy o any bariatric surgery including gastric bypass surgery, sleeve gastrectomy and gastric band o a contraindication to a high fibre diet (e.g. active diverticulitis or bowel obstruction) o allergy / intolerance to any ingredient in the fibre supplement o current and planned ongoing consumption of probiotic or prebiotic supplement o hepatitis B, hepatitis C or HIV infection unless viral load negative o on carbamazepine o inability to provide written informed consent [000104] Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures): The investigator recruiting participants will be unable to see which group they will be allocated to until after recruitment when the randomisation will be completed in REDCap. In REDCap future allocations are concealed. 2025200873 07 Feb 2025 [000105] Methods used to generate the sequence in which subjects will be randomised (sequence generation): Prior to study commencement, a randomisation table created by computer software will be entered into the REDCap database by an investigator not involved in recruitment. [000106] Masking / blinding: Open (masking not used) [000107] Phase: Phase 1 / Phase 2 [000108] Target number of patients: 30 Example 6: Clinical Trial - Treatment in Chimeric Antigen Receptor T cell Therapy [000109] Australian New Zealand Clinical Trial Registry No. ACTRN12625000056493p. [000110] A randomized controlled trial which studies the safety and feasibility of an oral prebiotic fibre supplement in Chimeric Antigen Receptor T cell (Car T) Therapy is to be conducted. [000111] Participants in this study will receive standard of care CAR T and be randomly assigned to either standard supportive care or receive an oral prebiotic fibre supplement in addition to supportive care. Participants will be followed up for up to 6 months to assess for feasibility and safety, and documented for clinical response, adverse events, and gastrointestinal symptoms to CAR T therapy. [000112] The trial compares oral prebiotic supplementation with Prebiotic Composition 2 (Example 2) (group 1 - Intervention arm patients) to standard care (group 2 - Control arm patients). Intervention arm patients receive an oral prebiotic fibre supplement in addition to standard of care CAR T and supportive care. The supplement will be taken twice per day from the day after collection of cells to manufacture CAR T until 30 days after CAR T administration (approximately 8-12 weeks supplementation period depending on CAR T manufacture time). [000113] Prebiotic Composition 2 is a powdered fibre supplement mix of inulin (4g), resistant starch (8g), and psyllium (3.5g) combined into a single serve sachet. Two sachets per day will provide a combined dose of 8g inulin, 16g resistant starch and 7g psyllium (providing 31g of supplement and a total of 22g fibre including 7g from inulin, 5g from psyllium and 10g from resistant starch). Adherence will be assessed by patient reporting as well as supplement sachet return. 2025200873 07 Feb 2025 [000114] Control arm patients (Group 2) receive standard of care CAR T therapy and supportive care. This includes standard commercial CAR T products available in Australia and supportive therapies required for CAR T administration including intravenous fluids, intravenous antibiotics and therapies to manage immune related toxicities as appropriate (including corticosteroids and other immune-modifying therapies). [000115] Outcomes of the trial include: Outcome Assessment method Timepoint To determine the feasibility of a dietary Prebiotic Fibre supplement (PFS) in CAR T therapy Adherence and dosage completion (defined as consuming >80% of the total number of PFS sachets prescribed for daily oral intake for up to 60-90 days). At day 0 at CAR T infusion, 7 days after CAR T infusion and 30 days after CAR T infusion when the supplement period ends. To determine the composite outcome of safety and tolerability of a dietary PFS in CAR T therapy. Adverse event grading according to standard CTCAE criteria v5.0 and patient reported outcome version (PRO-CTCAE). Possible adverse events include gastrointestinal symptoms including constipation / diarrhoea, bloating or abdominal pain / cramps. At day 0 at CAR T infusion, 7 days after CAR T infusion and 30 days after CAR T infusion when the supplement period ends. To determine the clinical response to CAR T therapy with oral dietary PFS. Standard disease response criteria performed routinely at day 30 and 6 months on Positron Emission Tomography / Computed Tomography (PET / CT) imaging (graded according to standardised Lugano criteria based on 5 point scale) 30 days and 6 months after CAR T infusion To determine the incidence and severity of immune-related adverse events with CAR T after oral dietary PFS. This will be assessed as a composite outcome. Incidence and severity of immune-related adverse events including cytokine release syndrome (CRS) and immune effector-cell associated neurotoxicity (ICANS) (graded according to standardised American Society of Transplantation and Cellular Therapy (ASTCT) criteria). Assessed within first 6 months after CAR T treatment. To determine the adequacy of dietary intake, nutritional status and incidence and severity of gastrointestinal symptoms. This will be Dietary intake - Monash CNAQ tool validated comprehensive nutritional assessment questionnaire Nutritional status - subjective global assessment Gastrointestinal symptoms - Patient Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) tool Within first 6 months after CAR T infusion 2025200873 07 Feb 2025 assessed as a composite outcome Assess quality of life Quality of life measures (EORTC QLQ-C30 questionnaire) 1 week and 1 month after CAR T infusion Overall survival after CAR T administration Overall survival or date of last follow up 6 months following end of treatment Length of hospital stay Length of hospital stay (assessed from electronic medical records) Within 6 months of CAR T administration Incidence of infection Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Within 6 months of CAR T administration Patients for the Trial - Age: age 18 years or older - Gender: Both males and females - Other inclusion criteria: o Planned recipient of CAR T cell therapy as part of standard of care indication (DLBCL, MCL, B-ALL and Myeloma) o Ability to provide voluntary informed consent o Willing and able to commence daily oral intake of PFS for potentially up to 90 days - Exclusion Criteria o healthy volunteer o Inflammatory bowel disease o Formal diagnosis of irritable bowel syndrome o Gastrointestinal resection, ileostomy or colostomy o Any bariatric surgery including gastric bypass surgery, sleeve gastrectomy and gastric band o Any other contraindication to a high fibre diet (e.g. active diverticulitis or bowel obstruction) o Allergy / intolerance to any ingredient in the PFS o Current and planned ongoing consumption of other probiotic or prebiotic supplements. o Hepatitis B, hepatitis C or HIV infection unless viral load negative o On carbamazepine o Enrolled in CAR T cell clinical trial 2025200873 07 Feb 2025 [000116] Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures): Central randomisation. [000117] Methods used to generate the sequence in which subjects will be randomised (sequence generation): Simple randomisation using a randomisation table created by computer software. [000118] Masking / blinding: Open (masking not used) [000119] Intervention assignment: Parallel [000120] Phase: Phase 1 [000121] Type of endpoint: Safety [000122] Target number of patients: 30 [000123] Although the invention has been described with reference to specific examples, it will be appreciated by those skilled in the art that the invention may be embodied in many other forms, and in particular features of any one of the various described examples may be provided in any combination in any of the other described examples. Various modifications and alterations to this invention will become apparent to those skilled in the art without departing from the scope and spirit of this invention. It should be understood that this invention is not intended to be unduly limited by the illustrative embodiments and examples set forth herein and that such examples and embodiments are presented by way of example only with the scope of the invention intended to be limited only by the claims set forth herein as follows. REFERENCES Andersen, S., Brown, T., Kennedy, G., & Banks, M. (2015). Implementation of an evidenced based nutrition support pathway for haematopoietic progenitor cell transplant patients. Clinical Nutrition, 34(3), 536-540. Barrett JSPMND, Gibson PRMDF. Development and Validation of a Comprehensive Semi-Quantitative Food Frequency Questionnaire that Includes FODMAP Intake and Glycemic Index. J Am Diet Assoc. 2010;110(10):1469-1476. Galloway-Pena J. and Hanson, B. Tools for Analysis of the Microbiome. Dig Dis Sci. 2021: 65(3): 674-685. 2025200873 07 Feb 2025 He Y, Fu L, Li Y, et al. Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8+ T cell immunity. Cell Metab. 2021;33(5):988-1000.e1007. Raigond, P., Ezekiel, R., & Raigond, B. (2015). Resistant starch in food: a review. J. Sci. Food Agric, 95(10), 1968-1978. https: / / doi.org / 10.1002 / jsfa.6966 Spencer CN, McQuade JL, Gopalakrishnan V, et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science. 2021;374(6575):1632-1640. Weng et al. Quantifying Gut Microbial Short-Chain Fatty Acids and Their Isotopomers in Mechanistic Studies Using a Rapid, Readily Expandable LC-MS Platform. Analytical Chemistry. 2024; 96:6, 2415-2424. Xie X, He Y, Li H, et al. Effects of prebiotics on immunologic indicators and intestinal microbiota structure in perioperative colorectal cancer patients. Nutrition. 2019;61:132-142.
Claims
2025200873 07 Feb 20251. A method of increasing fibre consumption in a subject in need thereof, comprisingadministering to the subject a composition comprising a fructan, a resistant starch and psyllium.
2. A method of: (i) promoting growth of short chain fatty acid producing bacteria in thegastrointestinal tract of a subject in need thereof; (ii) increasing short chain fatty acid production in the gastrointestinal tract of a subject in need thereof; and / or (iii) reducing the potential side effects associated with the consumption of fibre by a subject in need thereof;comprising administering to the subject a composition comprising a fructan, a resistant starch and psyllium.
3. The method of claim 2, wherein the short chain fatty acid is selected from the groupconsisting of one or more of butyrate, propionate and acetate.
4. The method of claim 2, wherein the short chain fatty acid producing bacteria may be oneor more selected from the group consisting of: Eubacterium species, Faecalibacterium species, Bifidobacterium species, Anaerostipes species, Roseburia species, Ruminococcus species and Anaerostipes species.
5. The method of any one of claims 1 to 4, wherein the subject has cancer.
6. The method of any one of claims 1 to 5, wherein the subject is receiving chemotherapy,immunotherapy and / or an antibiotic.
7. The method of claim 6, wherein the subject is receiving a chemotherapy or animmunotherapy for a haematological cancer.
8. The method of any one of claims 1 to 7, wherein the composition is administered at leasttwice per day.
9. The method of any one of claims 1 to 8, wherein the only source of fibres in thecomposition is a fructan, a resistant starch and psyllium.
10. The method of any one of claims 1 to 9, wherein the only fermentable fibres in the composition are a fructan and resistant starch.
11. The method of any one of claims 1 to 10, where the fructan is inulin.2025200873 07 Feb 202512. The method of any one of claims 1 to 11, wherein the ratio (by weight) of psyllium : resistant starch and fructan in the composition is from 1:2 to 1:5.
13. The method of any one of claims 1 to 12, wherein the ratio of fructan to resistant starch is from 1:0.5 to 1:
314. The method of any one of claims 1 to 13, wherein the subject is administered:From 2-10 g / day inulin;From 2-22 g / day resistant starch; andFrom 2-10 g / day psyllium.
15. Use of a fructan, a resistant starch and psyllium in the manufacture of a medicament for increasing fibre consumption in a subject in need thereof.
16. Use of a fructan, a resistant starch and psyllium in the manufacture of a medicament for: (i) promoting growth of short chain fatty acid producing bacteria in the gastrointestinal tract of a subject in need thereof; (ii) increasing short chain fatty acid production in the gastrointestinal tract of a subject in need thereof; and / or (iii) reducing the potential side effects associated with the consumption of fibre by a subject in need thereof.
17. A composition comprising a fructan, a resistant starch and psyllium.
18. The composition of claim 17, wherein the fructan is inulin.
19. The composition of claim 17 or claim 18, wherein the composition comprises from 45-80wt% of fructan and resistant starch.
20. The composition of any one of claims 17 to 19, wherein the composition comprises from 13-30 wt% psyllium.
21. The composition of any one of claims 17 to 20, wherein the composition comprisesFrom 20-60 wt% resistant starch;From 15-32 wt% inulin; andFrom 10-30 wt% psyllium.