WO2024091672A1 - Methods of preventing, delaying or ameliorating pediatric atopic disease - Google Patents
Methods of preventing, delaying or ameliorating pediatric atopic disease Download PDFInfo
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- WO2024091672A1 WO2024091672A1 PCT/US2023/036135 US2023036135W WO2024091672A1 WO 2024091672 A1 WO2024091672 A1 WO 2024091672A1 US 2023036135 W US2023036135 W US 2023036135W WO 2024091672 A1 WO2024091672 A1 WO 2024091672A1
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Classifications
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- A—HUMAN NECESSITIES
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- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
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- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/745—Bifidobacteria
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/05—Actinobacteria, e.g. Actinomyces, Streptomyces, Nocardia, Bifidobacterium, Gardnerella, Corynebacterium; Propionibacterium
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P37/00—Drugs for immunological or allergic disorders
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Definitions
- the present disclosure generally relates to compositions and methods of preventing, delaying or ameliorating atopic disease, such as food allergy, and particularly to methods including administering a composition having an effective amount of a Bifidobacterium and at least one glycan to an infant during gestation or after birth.
- atopic disease such as food allergy
- BACKGROUND The prevalence of pediatric allergic disease, also known as atopic disease, is increasing globally with many children suffering from eczema (i.e., atopic dermatitis) and/or allergies to at least one food.
- Atopic disease represents a failure of immune tolerance and a subsequent overreaction to benign inhalant (i.e., environmental) or food allergens. While there is substantial research into the potential genetic, metabolomic, environmental, and socioeconomic predictive correlates of atopic disease, current clinical guidance for allergic disease focuses on avoidance of allergens and acute treatment of exacerbations and not on prevention. [0003] Prevention of pediatric atopic disease requires addressing several causes that result in immune system dysregulation and failure of establishment or maintenance of immune tolerance.
- a disordered skin barrier either in the presence or absence of eczema and an altered skin microbiome enables food and inhalant allergens to sensitize the infant with generation of immune cells that migrate to the gut or lung to lead to food allergy or asthma, respectively.
- infants born in the modernized world lack important keystone gut microbes and thus their functionality arising from antibiotic exposure, C-section delivery, lack of breastfeeding, and/or trans-generation effects of their mothers exposed to the same insults.
- This gut dysbiotic microbiome fails to induce a tolerogenic state and results in a pro-inflammatory environment that mis-characterizes benign antigens.
- the present disclosure provides methods for preventative treatment of pediatric allergic disease through administration of a composition including a Bifidobacterium and at least one glycan.
- the composition can be administered prenatally during gestation of the infant or after birth of the infant.
- the present disclosure provides methods of preventing, delaying or ameliorating atopic disease in an infant.
- the method includes administering a composition comprising an effective amount of a Bifidobacterium and at least one glycan to the infant.
- the Bifidobacterium can be from the group B. longum.
- the Bifidobacterium can be a B. longum subspecies infantis.
- the at least one glycan can include a plant-based glycan.
- the at least one glycan can include an asparagine linked glycan (N-glycan).
- the at least one glycan can be peanut.
- the at least one glycan can be in the form of a powder.
- the infant can be breastfed, formula fed, or a combination thereof.
- the infant can be about 12 months old or less.
- the infant can be about 6 months old or less.
- the composition can be first administered to the infant within the first two weeks of life.
- the composition can be administered daily.
- the atopic disease can be atopic dermatitis, food allergy, allergic rhinitis, asthma, or combinations thereof.
- the present disclosure further provides methods for preventing, delaying or CONSJCO6209WOPCT1 ameliorating atopic disease in an infant.
- the method includes prenatally administering to the mother of the infant a composition comprising an effective amount of a Bifidobacterium and at least one glycan during gestation of the infant.
- the Bifidobacterium can be from the group B. longum.
- the Bifidobacterium can be a B. longum subspecies infantis.
- about 5 billion CFU to about 10 billion CFU of the Bifidobacterium can be administered to the infant.
- the at least one glycan can include a plant-based glycan.
- the at least one glycan can include an asparagine-linked glycan (N-glycan).
- N-glycan asparagine-linked glycan
- the at least one glycan can be peanut.
- the at least one glycan can be in the form of a powder.
- the composition can be administered daily.
- the atopic disease can be atopic dermatitis, food allergy, allergic rhinitis, asthma, or combinations thereof. [00030]
- compositions and methods of preventing, delaying, or ameliorating pediatric atopic disease include the administration of a composition including a Bifidobacterium and at least one glycan.
- the composition can be administered prenatally during gestation of the infant or after birth of the infant.
- methods of the present disclosure advantageously provide for prevention, delay, or amelioration of atopic disease rather than avoidance of allergens or acute treatment of exacerbations from the same.
- the present disclosure provides improved synbiotic compositions (e.g., including Bifidobacterium and one or more glycans) for infant immune training in order to decrease risk of pediatric atopic disease in infants independent of the presence of breast milk human milk oligosaccharides (HMOs).
- HMOs breast milk human milk oligosaccharides
- administering refers to providing a given dose of Bifidobacterium to infants as part of their feeding or prenatally to its mother (i.e., it is used as food supplement).
- the conjunctive term “and/or” between multiple recited elements is understood as encompassing both individual and combined options. For instance, where two elements are conjoined by “and/or”, a first option refers to the applicability of the first element without the second. A second option refers to the applicability of the second element without the first. A third option refers to the applicability of the first and second elements together. Any one of these options is understood to fall within the meaning, and therefore satisfy the requirement of the term “and/or” as used herein.
- atopic dermatitis or “eczema” refers to chronic relapsing inflammatory skin disorder that makes skin itchy and/or red. Pruritus or itchy skin is a primary symptom of atopic dermatitis, which can also have skin lesions ranging from mild erythema to severe lichenification to erythroderma. It is common in children but can occur at any age. Atopic dermatitis may be accompanied by asthma or hay fever. There is currently no cure for atopic dermatitis.
- atopic disease and “allergic disease” can be used CONSJCO6209WOPCT1 interchangeably.
- Atopic diseases are a class of diseases in which the immune system develops Immunoglobulin IgE to common environmental allergens which are generally considered to be harmless. Examples of atopic diseases include, but not limited to, atopic dermatitis, allergic rhinitis, asthma, and food allergy.
- Bifidobacterium infantis or “B. infantis” refers to the subspecies of Bifidobacterium longum subsp. infantis. B. Infantis can be isolated and cultured using methods known in the art.
- breastfed means that the infant derives at least some of its sustenance from human breastmilk.
- the infant can either nurse or the breastmilk can be expressed (e.g., pumped or hand-expressed) and given to the infant.
- the breastfed infant can be at least about 50%, 60%, 75%, 80%, 90% or 95% breastfed.
- the infant can be exclusively breastfed.
- exclusively breastfed means that the infant does not receive infant formula. Any caloric contribution form other sources during the first 3 months of life, including medicines, the composition, or any medium used to deliver the composition, is considered negligible.
- the terms “comprises,” “comprising,” or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but can include other elements not expressly listed or inherent to such process, method, article, or apparatus.
- the term “effective amount” refers to an amount of a regimen and/or composition sufficient to significantly induce a positive benefit, including independently or in combination with other benefits disclosed herein.
- the content and/or concentration of active component in the regimen and/or composition is sufficient that when the regimen and/or composition is applied with normal frequency and in a normal amount, the regimen and/or composition can result in treating or reducing the onset or occurrence of childhood atopic disease.
- the effective amount of the compound, extract, or composition will vary with, e.g., the age, health and environmental exposure of the end user, the duration and nature of the treatment, the specific extract, ingredient, or composition employed, the particular pharmaceutically-acceptable carrier utilized, and like factors.
- the term “essentially free” or “substantially free” of an ingredient CONSJCO6209WOPCT1 means containing less than 0.1 weight percent, or less than 0.01 weight percent, or none of an ingredient.
- the term “infant” refers to a human whose age ranges from birth to approximately twelve months of life.
- the term “increased risk of developing an atopic disease” refers to an infant having one first-degree relative having a history of atopic disease (i.e., biological parent or full sibling with mother-reported, physician-diagnosed atopic dermatitis, allergic rhinitis or asthma. The infant can be born either vaginally or via C-section.
- atopic disease i.e., biological parent or full sibling with mother-reported, physician-diagnosed atopic dermatitis, allergic rhinitis or asthma.
- the infant can be born either vaginally or via C-section.
- One aspect of the present disclosure relates to a method of preventing, delaying or ameliorating an atopic disease in an infant.
- the method includes administering a composition comprising an effective amount of a Bifidobacterium and at least one glycan to the infant.
- Another aspect of the present disclosure provides a method of preventing, delaying or ameliorating atopic disease in an infant in which the method incudes prenatally administering a composition comprising an effective amount of a Bifidobacterium and at least one glycan during gestation of the infant.
- the atopic disease can be atopic dermatitis, food allergy, allergic rhinitis, asthma, or combinations thereof.
- the atopic disease may be selected from the group consisting of food allergy, allergic rhinitis, asthma, and combinations thereof.
- the atopic disease may be atopic dermatitis (AD), AD, which arises from a combination of defective epidermal skin barrier function, T-cell activation, and dysbiosis of skin commensal microbes, may precede the onset of other atopic disease, e.g., food allergy, asthma, and allergic rhinitis, in the so-called “atopic march.” Owing to transcutaneous allergic sensitization through eczematous skin, approximately one-third of children with AD develop food allergy.
- AD atopic dermatitis
- a unique AD endotype associated with food allergy has been identified and is characterized by altered terminal epidermal differentiation with changes in collagen expression, T-helper 2 (Th2) immune transcripts, poor skin barrier function, and predisposition to cutaneous Staphylococcus aureus colonization and infection.
- the infant gut microbiome trains the immune system for health and prevention of disease. Healthy infant gut microbiome can be established by the abundance and functionality of the optimal microbes, which can be supported by matching prebiotics.
- Certain Bifidobacterium such as B. infantis are a keystone infant gut microbiome that has been shown to train the infant immune system, however, this particular microbe has disappeared with modernization. B.
- infantis abundance and function can be supported by breast milk human milk oligosaccharides (HMOs) mediated by B. infantis HMO utilization genes.
- B. infantis abundance and function can also be supported by glycans if B. infantis expresses unique carbohydrate active enzymes (CAZymes).
- CAZymes of B. infantis can metabolize glycans including glycoside hydrolases that can metabolize beta-1,3-linked glucosides.
- Asparagine-linked glycans (N-glycans) have structural similarity to HMOs and B. infantis can metabolize such through N-glycan utilization genes.
- N- glycans can be a component of the diet of an infant.
- Peanut contains glycans typically introduced in early childhood to promote immune tolerance in order to decrease risk of peanut food allergy.
- the present disclosure is directed to an improved synbiotic regimen of B. infantis that can metabolize N-glycans such as peanut to support B. infantis growth and function in non-breastfed infants and promote health in all infants independent of breastfeeding.
- Improvements with respect to any of the above conditions can be measured by CONSJCO6209WOPCT1 known methods in the art. For example, improvement in the severity of atopic dermatitis can be measured using the Eczema Area and Severity Index (EASI). Improvements or amelioration can be with respect to the condition in an infant without being treated with the composition.
- EASI Eczema Area and Severity Index
- the composition can include a Bifidobacterium and at least one glycan.
- Bifidobacterium is a genus of a gram-positive, anaerobic bacteria, which reside in the gastrointestinal, vaginal, and oral tracts of mammals, including humans.
- the suitable Bifidobacterium can be those having at least one human milk oligosaccharides (HMO) gene cluster.
- HMO human milk oligosaccharides
- the Bifidobacterium can be one that is similar to B. infantis. In one or more embodiments, wherein the Bifidobacterium is selected from the group consisting of B. longum, B. breve, B. bifidum, B.
- pseudocatenulatum B. globosum, B. adolescentis, B. moukalabense, B. reuteri, B. pseudolongum, B. dentium, B. catenulatum, B. sp002742445, B. callitrichos, B. scardovii, B. tissieri, B. subtile, B. gallinarum, B. choerinum, B. angulatum, B. primatium, B. myosotis, B. mongoliense, B. merycicum, B. lemurum, B. staboschense, B. scaligerum, B. saguini, B. pullorum, B. felsineum, B.
- the Bifidobacterium is selected from the group consisting of B. longum, B. breve, B. kashiwanohense and combinations thereof. In one or more embodiments, wherein the Bifidobacterium is a B. longum subspecies selected from the group consisting of longum, suis, infantis, and combinations thereof. In some embodiments, wherein the Bifidobacterium is B. infantis. In one or more embodiments, where in the Bifidobacterium comprises the strain EVC001. In certain embodiments, the Bifidobacterium can be administered without any other probiotics.
- the Bifidobacterium can be formulated to be essentially free of any other probiotics.
- the infants gut microbiome profile can be tested and monitored to determine colonization by Bifidobacterium using methods known in the art. Stool samples can be used in such methods.
- the Bifidobacterium can be included in the composition which is east to use and CONSJCO6209WOPCT1 allows for consistent dosing.
- the fermentation product from Bifidobacterium production can be concentrated and freeze dried to provide a concentrated powder.
- the composition can include about 1 million, about 500 million, about 1 billion, 2 billion, 3 billion, 4 billion, 5 billion, 6 billion, 7 billion, 8 billion, 9 billion, 10 billion, or 12 billion to about 8 billion, 9 billion, 10 billion, 20 billion, 30 billion, 40 billion, 50 billion, 60 billion, 70 billion, 80 billion, 90 billion, 100 billion, 200 billion, 250 billion, or 500 billion colony forming units (CFU) of Bifidobacterium per gram dry weight.
- CFU colony forming units
- the composition can include one or more glycans.
- glycan refers to carbohydrate-based polymers, also known as polysaccharides, and particularly those capable of aiding the growth of the Bifidobacterium and/or colonization of a gut by the Bifidobacterium.
- the one or more glycans can be a plant-based glycans.
- the one or more glycans can be an asparagine-linked glycan (N- glycan).
- the one or more glycans are derived from legumes, particularly peanut.
- the one or more glycans can be in the form of a powder.
- compositions containing Bifidobacterium can further include an auxiliary component.
- auxiliary components are those commonly used in the art and can be selected from metabolites, flow agents or combinations thereof. Examples of flow agents include starch, silicon dioxide, cellulose, sodium bicarbonate, calcium silicate and the like.
- the final form of the composition can be any known in the art.
- the Bifidobacterium can be in dried form (e.g., spray-dried or freeze-dried) as a powder.
- Said powder can be dosed as a packet, sachet, tablet, foodstuff, capsule, lozenge, suspension, dry form, etc.
- Administration [00061]
- One aspect of the present disclosure provides administration of the composition of to the infant after birth.
- Another aspect of the present disclosure provides prenatal administration of the composition to the infant during gestation.
- the dose and dosing frequency can be selected as desired.
- the CONSJCO6209WOPCT1 composition can be administered once daily.
- the dose once daily can contain from about 5-10 billion or about 8 billion CFU.
- the total dose given per day can range from about 1 million, 500 million, 1 billion, 2 billion, 3 billion, 4 billion, 5 billion, 6 billion, 7 billion, 8 billion, 8 billion, 10 billion or 12 billion to about 8 billion, 9 billion, 10 billion, 20 billion, 30 billion, 40 billion, 50 billion, 60 billion, 70 billion, 80 billion, 90 billion, 100 billion, 200 billion, 250 billion or 500 billion colony forming units (CFUs) of the Bifidobacterium.
- CFUs colony forming units
- the total dose given per day can range from about 5 billion CFU to about 10 billion CFU, or be about 8 billion CFU. Such total dose values can be given in one dose.
- the composition can be administered within the first 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 weeks of life or beginning with the first 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months of life.
- the composition can be first administered within the first 2 weeks of life.
- the composition can be administered within the first 2 weeks of life and until the 12th week of life.
- the composition can be administered to an infant aged 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 month old or less.
- the composition can be administered to an infant aged 12 months or less or 3 months or less.
- the infant can be breastfed, formula fed, or a combination thereof.
- the infant can derive at least some of its sustenance from human breastmilk.
- the infant can either nurse or the breastmilk can be expressed (e.g., pumped or hand-expressed) and given to the infant.
- the breastfed infant can be at least about 50%, 60%, 75%, 80%, 90% or 95% breastfed.
- the remainder of the infant’s sustenance can be derived from infant formula or other food.
- the breastfed infant can be exclusively breastfed and not receive infant formula. Any caloric contribution from other sources during the first 3 months of life, including medicines, the composition, or any medium used to deliver the composition is considered negligible.
- the infant can be exclusively formula fed.
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Abstract
Compositions and methods of preventing, delaying, or ameliorating atopic diseases, such as food allergy, the methods comprising administering a composition having an effective amount of a Bifidobacterium and at least one glycan to an infant during gestation or after birth.
Description
CONSJCO6209WOPCT1 METHODS OF PREVENTING, DELAYING OR AMELIORATING PEDIATRIC ATOPIC DISEASE 1. FIELD [0001] The present disclosure generally relates to compositions and methods of preventing, delaying or ameliorating atopic disease, such as food allergy, and particularly to methods including administering a composition having an effective amount of a Bifidobacterium and at least one glycan to an infant during gestation or after birth. 2. BACKGROUND [0002] The prevalence of pediatric allergic disease, also known as atopic disease, is increasing globally with many children suffering from eczema (i.e., atopic dermatitis) and/or allergies to at least one food. Atopic disease represents a failure of immune tolerance and a subsequent overreaction to benign inhalant (i.e., environmental) or food allergens. While there is substantial research into the potential genetic, metabolomic, environmental, and socioeconomic predictive correlates of atopic disease, current clinical guidance for allergic disease focuses on avoidance of allergens and acute treatment of exacerbations and not on prevention. [0003] Prevention of pediatric atopic disease requires addressing several causes that result in immune system dysregulation and failure of establishment or maintenance of immune tolerance. In early infancy, a disordered skin barrier either in the presence or absence of eczema and an altered skin microbiome enables food and inhalant allergens to sensitize the infant with generation of immune cells that migrate to the gut or lung to lead to food allergy or asthma, respectively. Additionally, infants born in the modernized world lack important keystone gut microbes and thus their functionality arising from antibiotic exposure, C-section delivery, lack of breastfeeding, and/or trans-generation effects of their mothers exposed to the same insults. This gut dysbiotic microbiome fails to induce a tolerogenic state and results in a pro-inflammatory environment that mis-characterizes benign antigens. Finally, there is typically a delay of food introduction in infancy that is required for optimal immune training of infants for specific foods (e.g., peanut). [0004] While individual solutions such as probiotics and food introduction products have been developed, there remains a need for an easy-to-use integrated solution for optimal effectiveness in prevention of pediatric allergic disease such as eczema (i.e., atopic dermatitis), food allergy, and
CONSJCO6209WOPCT1 asthma, with options for administration prenatally or after birth of the infant. The present disclosure addresses these and other needs. 3. SUMMARY [0005] The present disclosure relates to compositions and methods of preventing, delaying, or ameliorating pediatric atopic disease, such as food allergy. In particular, the present disclosure provides methods for preventative treatment of pediatric allergic disease through administration of a composition including a Bifidobacterium and at least one glycan. The composition can be administered prenatally during gestation of the infant or after birth of the infant. [0006] The present disclosure provides methods of preventing, delaying or ameliorating atopic disease in an infant. The method includes administering a composition comprising an effective amount of a Bifidobacterium and at least one glycan to the infant. [0007] In certain embodiments, the Bifidobacterium can be from the group B. longum. [0008] In certain embodiments, the Bifidobacterium can be a B. longum subspecies infantis. [0009] In certain embodiments, about 5 billion CFU to about 10 billion CFU of the Bifidobacterium can be administered to the infant. [00010] In certain embodiments, the at least one glycan can include a plant-based glycan. [00011] In certain embodiments, the at least one glycan can include an asparagine linked glycan (N-glycan). [00012] In certain embodiments, the at least one glycan can be peanut. [00013] In certain embodiments, the at least one glycan can be in the form of a powder. [00014] In certain embodiments, the infant can be breastfed, formula fed, or a combination thereof. [00015] In certain embodiments, the infant can be about 12 months old or less. [00016] In certain embodiments, the infant can be about 6 months old or less. [00017] In certain embodiments, the composition can be first administered to the infant within the first two weeks of life. [00018] In certain embodiments, the composition can be administered daily. [00019] In certain embodiments, the atopic disease can be atopic dermatitis, food allergy, allergic rhinitis, asthma, or combinations thereof. [00020] The present disclosure further provides methods for preventing, delaying or
CONSJCO6209WOPCT1 ameliorating atopic disease in an infant. The method includes prenatally administering to the mother of the infant a composition comprising an effective amount of a Bifidobacterium and at least one glycan during gestation of the infant. [00021] In certain embodiments, the Bifidobacterium can be from the group B. longum. [00022] In certain embodiments, the Bifidobacterium can be a B. longum subspecies infantis. [00023] In certain embodiments, about 5 billion CFU to about 10 billion CFU of the Bifidobacterium can be administered to the infant. [00024] In certain embodiments, the at least one glycan can include a plant-based glycan. [00025] In certain embodiments, the at least one glycan can include an asparagine-linked glycan (N-glycan). [00026] In certain embodiments, the at least one glycan can be peanut. [00027] In certain embodiments, the at least one glycan can be in the form of a powder. [00028] In certain embodiments, the composition can be administered daily. [00029] In certain embodiments, the atopic disease can be atopic dermatitis, food allergy, allergic rhinitis, asthma, or combinations thereof. [00030] These and other features and advantages of the present disclosure will be readily apparent from the following detailed description. 4. DETAILED DESCRIPTION [00031] The presently disclosed subject matter relates to compositions and methods of preventing, delaying, or ameliorating pediatric atopic disease. Such methods include the administration of a composition including a Bifidobacterium and at least one glycan. The composition can be administered prenatally during gestation of the infant or after birth of the infant. In certain aspects, methods of the present disclosure advantageously provide for prevention, delay, or amelioration of atopic disease rather than avoidance of allergens or acute treatment of exacerbations from the same. Thus, the present disclosure provides improved synbiotic compositions (e.g., including Bifidobacterium and one or more glycans) for infant immune training in order to decrease risk of pediatric atopic disease in infants independent of the presence of breast milk human milk oligosaccharides (HMOs). [00032] These and other aspects of the disclosed subject matter are discussed in more detail
CONSJCO6209WOPCT1 below. For clarity, and not by way of limitation, this detailed description is divided into the following sub-portions: 4.1. Definitions; and 4.2. Methods of preventing, delaying or ameliorating atopic disease. 4.1. Definitions [00033] The terms used in this specification generally have their ordinary meanings in the art within the context of this disclosure and in specific context where each term is used. Certain terms are discussed below, or elsewhere in the specification, to provide additional guidance in describing the compositions and methods of the disclosure and how to make and use them. [00034] As used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural reference unless the context clearly dictates otherwise. [00035] As used herein, the term “administering” refers to providing a given dose of Bifidobacterium to infants as part of their feeding or prenatally to its mother (i.e., it is used as food supplement). [00036] As used herein, the conjunctive term “and/or” between multiple recited elements is understood as encompassing both individual and combined options. For instance, where two elements are conjoined by “and/or”, a first option refers to the applicability of the first element without the second. A second option refers to the applicability of the second element without the first. A third option refers to the applicability of the first and second elements together. Any one of these options is understood to fall within the meaning, and therefore satisfy the requirement of the term “and/or” as used herein. Concurrent applicability of more than one of the options is also understood to fall within the meaning, and therefore satisfy the requirement of the term “and/or.” [00037] As used herein, the term “atopic dermatitis” or “eczema” refers to chronic relapsing inflammatory skin disorder that makes skin itchy and/or red. Pruritus or itchy skin is a primary symptom of atopic dermatitis, which can also have skin lesions ranging from mild erythema to severe lichenification to erythroderma. It is common in children but can occur at any age. Atopic dermatitis may be accompanied by asthma or hay fever. There is currently no cure for atopic dermatitis. [00038] As used herein, the terms “atopic disease” and “allergic disease” can be used
CONSJCO6209WOPCT1 interchangeably. Atopic diseases are a class of diseases in which the immune system develops Immunoglobulin IgE to common environmental allergens which are generally considered to be harmless. Examples of atopic diseases include, but not limited to, atopic dermatitis, allergic rhinitis, asthma, and food allergy. [00039] As used herein, the term “Bifidobacterium infantis” or “B. infantis” refers to the subspecies of Bifidobacterium longum subsp. infantis. B. Infantis can be isolated and cultured using methods known in the art. [00040] As used herein, the term “breastfed” means that the infant derives at least some of its sustenance from human breastmilk. The infant can either nurse or the breastmilk can be expressed (e.g., pumped or hand-expressed) and given to the infant. The breastfed infant can be at least about 50%, 60%, 75%, 80%, 90% or 95% breastfed. Alternatively, the infant can be exclusively breastfed. As used herein the term “exclusively breastfed” means that the infant does not receive infant formula. Any caloric contribution form other sources during the first 3 months of life, including medicines, the composition, or any medium used to deliver the composition, is considered negligible. [00041] As used herein, the terms “comprises,” “comprising,” or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but can include other elements not expressly listed or inherent to such process, method, article, or apparatus. [00042] As used herein, the term “effective amount” refers to an amount of a regimen and/or composition sufficient to significantly induce a positive benefit, including independently or in combination with other benefits disclosed herein. This means that the content and/or concentration of active component in the regimen and/or composition is sufficient that when the regimen and/or composition is applied with normal frequency and in a normal amount, the regimen and/or composition can result in treating or reducing the onset or occurrence of childhood atopic disease. The effective amount of the compound, extract, or composition will vary with, e.g., the age, health and environmental exposure of the end user, the duration and nature of the treatment, the specific extract, ingredient, or composition employed, the particular pharmaceutically-acceptable carrier utilized, and like factors. [00043] As used herein, the term “essentially free” or “substantially free” of an ingredient
CONSJCO6209WOPCT1 means containing less than 0.1 weight percent, or less than 0.01 weight percent, or none of an ingredient. [00044] As used herein, the term “infant” refers to a human whose age ranges from birth to approximately twelve months of life. [00045] As used herein, the term “increased risk of developing an atopic disease” refers to an infant having one first-degree relative having a history of atopic disease (i.e., biological parent or full sibling with mother-reported, physician-diagnosed atopic dermatitis, allergic rhinitis or asthma. The infant can be born either vaginally or via C-section. [00046] To provide a more concise description, some of the quantitative expressions given herein are not quantified with the term “about”. It is understood that whether the term “about” is used explicitly or not, every quantity herein is meant to refer to the actual given value, and it is also meant to refer to the approximation to such given value that would reasonable be inferred based on the ordinary skill in the art, including approximations due to the experimental and/or measurement conditions for such given value. [00047] To provide a more concise description, some of the quantitative expressions herein are recited as a range from about amount X to about amount Y. It is understood that wherein a range is recited, the range is not limited to the recited upper and lower bounds, but rather includes the full range from about amount X through about amount Y, or any amount or range therein. [00048] All percentages, parts and ratios are based upon the total weight of the composition of the present invention, unless otherwise specified. All such weights as they pertain to listed ingredients are based on the level of the particular ingredient described and, therefore, do not include carriers or by-products that may be included in commercially available materials, unless otherwise specified. 4.2. Methods of Preventing, Delaying or Ameliorating Atopic Disease [00049] One aspect of the present disclosure relates to a method of preventing, delaying or ameliorating an atopic disease in an infant. The method includes administering a composition comprising an effective amount of a Bifidobacterium and at least one glycan to the infant. Another aspect of the present disclosure provides a method of preventing, delaying or ameliorating atopic disease in an infant in which the method incudes prenatally administering a composition comprising an effective amount of a Bifidobacterium and at least one glycan during gestation of the infant. In
CONSJCO6209WOPCT1 certain aspects, the atopic disease can be atopic dermatitis, food allergy, allergic rhinitis, asthma, or combinations thereof. [00050] The atopic disease may be selected from the group consisting of food allergy, allergic rhinitis, asthma, and combinations thereof. The atopic disease may be atopic dermatitis (AD), AD, which arises from a combination of defective epidermal skin barrier function, T-cell activation, and dysbiosis of skin commensal microbes, may precede the onset of other atopic disease, e.g., food allergy, asthma, and allergic rhinitis, in the so-called “atopic march.” Owing to transcutaneous allergic sensitization through eczematous skin, approximately one-third of children with AD develop food allergy. In fact, a unique AD endotype associated with food allergy has been identified and is characterized by altered terminal epidermal differentiation with changes in collagen expression, T-helper 2 (Th2) immune transcripts, poor skin barrier function, and predisposition to cutaneous Staphylococcus aureus colonization and infection. [00051] The infant gut microbiome trains the immune system for health and prevention of disease. Healthy infant gut microbiome can be established by the abundance and functionality of the optimal microbes, which can be supported by matching prebiotics. Certain Bifidobacterium such as B. infantis are a keystone infant gut microbiome that has been shown to train the infant immune system, however, this particular microbe has disappeared with modernization. B. infantis abundance and function can be supported by breast milk human milk oligosaccharides (HMOs) mediated by B. infantis HMO utilization genes. B. infantis abundance and function can also be supported by glycans if B. infantis expresses unique carbohydrate active enzymes (CAZymes). CAZymes of B. infantis can metabolize glycans including glycoside hydrolases that can metabolize beta-1,3-linked glucosides. Asparagine-linked glycans (N-glycans) have structural similarity to HMOs and B. infantis can metabolize such through N-glycan utilization genes. N- glycans can be a component of the diet of an infant. Peanut contains glycans typically introduced in early childhood to promote immune tolerance in order to decrease risk of peanut food allergy. As such, the present disclosure is directed to an improved synbiotic regimen of B. infantis that can metabolize N-glycans such as peanut to support B. infantis growth and function in non-breastfed infants and promote health in all infants independent of breastfeeding. [00052] Improvements with respect to any of the above conditions can be measured by
CONSJCO6209WOPCT1 known methods in the art. For example, improvement in the severity of atopic dermatitis can be measured using the Eczema Area and Severity Index (EASI). Improvements or amelioration can be with respect to the condition in an infant without being treated with the composition. Composition [00053] In certain embodiments, the composition can include a Bifidobacterium and at least one glycan. [00054] Bifidobacterium is a genus of a gram-positive, anaerobic bacteria, which reside in the gastrointestinal, vaginal, and oral tracts of mammals, including humans. The suitable Bifidobacterium can be those having at least one human milk oligosaccharides (HMO) gene cluster. The Bifidobacterium can be one that is similar to B. infantis. In one or more embodiments, wherein the Bifidobacterium is selected from the group consisting of B. longum, B. breve, B. bifidum, B. pseudocatenulatum, B. globosum, B. adolescentis, B. moukalabense, B. reuteri, B. pseudolongum, B. dentium, B. catenulatum, B. sp002742445, B. callitrichos, B. scardovii, B. tissieri, B. subtile, B. gallinarum, B. choerinum, B. angulatum, B. primatium, B. myosotis, B. mongoliense, B. merycicum, B. lemurum, B. stellenboschense, B. scaligerum, B. saguini, B. pullorum, B. felsineum, B. eulemuris, B. cuniculi, B. callitrichos_A, B. biavatii, B. anseris, B. vansinderenii, B. sp900551485, B. sp003952945, B. sp003952025, B. sp003952005, B. simiarum, B. pseudolongum_C, B. parmae, B. margollesii, B. kashiwanohense_A, B. italicum, B. imperatoris, B. cricetid, B. catulorum, B. callitrichidarum, B. animalis, B. aesculapii, and combinations thereof. In some embodiments, wherein the Bifidobacterium is selected from the group consisting of B. longum, B. breve, B. kashiwanohense and combinations thereof. In one or more embodiments, wherein the Bifidobacterium is a B. longum subspecies selected from the group consisting of longum, suis, infantis, and combinations thereof. In some embodiments, wherein the Bifidobacterium is B. infantis. In one or more embodiments, where in the Bifidobacterium comprises the strain EVC001. In certain embodiments, the Bifidobacterium can be administered without any other probiotics. For example, in particular embodiments, the Bifidobacterium can be formulated to be essentially free of any other probiotics. [00055] The infants gut microbiome profile can be tested and monitored to determine colonization by Bifidobacterium using methods known in the art. Stool samples can be used in such methods. [00056] The Bifidobacterium can be included in the composition which is east to use and
CONSJCO6209WOPCT1 allows for consistent dosing. The fermentation product from Bifidobacterium production can be concentrated and freeze dried to provide a concentrated powder. The composition can include about 1 million, about 500 million, about 1 billion, 2 billion, 3 billion, 4 billion, 5 billion, 6 billion, 7 billion, 8 billion, 9 billion, 10 billion, or 12 billion to about 8 billion, 9 billion, 10 billion, 20 billion, 30 billion, 40 billion, 50 billion, 60 billion, 70 billion, 80 billion, 90 billion, 100 billion, 200 billion, 250 billion, or 500 billion colony forming units (CFU) of Bifidobacterium per gram dry weight. [00057] In certain embodiments, the composition can include one or more glycans. As used herein, “glycan” refers to carbohydrate-based polymers, also known as polysaccharides, and particularly those capable of aiding the growth of the Bifidobacterium and/or colonization of a gut by the Bifidobacterium. In certain embodiments, the one or more glycans can be a plant-based glycans. In certain embodiments, the one or more glycans can be an asparagine-linked glycan (N- glycan). In one or more embodiments, the one or more glycans are derived from legumes, particularly peanut. The one or more glycans can be in the form of a powder. It is noted that other components may also be contained along with the peanut glycans as a byproduct of processing a peanut ingredient (e.g., the composition may also include peanut proteins, fats, etc. naturally occurring in peanut). [00058] In certain aspects, it is contemplated that other B. infantis strains can be applicable that can metabolize glycans introduced early in childhood can be used. [00059] The composition containing Bifidobacterium can further include an auxiliary component. Such auxiliary components are those commonly used in the art and can be selected from metabolites, flow agents or combinations thereof. Examples of flow agents include starch, silicon dioxide, cellulose, sodium bicarbonate, calcium silicate and the like. [00060] The final form of the composition can be any known in the art. As described above, the Bifidobacterium can be in dried form (e.g., spray-dried or freeze-dried) as a powder. Said powder can be dosed as a packet, sachet, tablet, foodstuff, capsule, lozenge, suspension, dry form, etc. Administration [00061] One aspect of the present disclosure provides administration of the composition of to the infant after birth. Another aspect of the present disclosure provides prenatal administration of the composition to the infant during gestation. [00062] The dose and dosing frequency can be selected as desired. For example, the
CONSJCO6209WOPCT1 composition can be administered once daily. In such an example, the dose once daily can contain from about 5-10 billion or about 8 billion CFU. Splitting the total desired dose into smaller doses is also contemplated. Examples could include smaller doses is also contemplated. Examples could include doses several times throughout the da (e.g., 2, 3, 4 or 5 times per day). [00063] The total dose given per day can range from about 1 million, 500 million, 1 billion, 2 billion, 3 billion, 4 billion, 5 billion, 6 billion, 7 billion, 8 billion, 8 billion, 10 billion or 12 billion to about 8 billion, 9 billion, 10 billion, 20 billion, 30 billion, 40 billion, 50 billion, 60 billion, 70 billion, 80 billion, 90 billion, 100 billion, 200 billion, 250 billion or 500 billion colony forming units (CFUs) of the Bifidobacterium. The total dose given per day can range from about 5 billion CFU to about 10 billion CFU, or be about 8 billion CFU. Such total dose values can be given in one dose. [00064] The composition can be administered within the first 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 weeks of life or beginning with the first 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months of life. The composition can be first administered within the first 2 weeks of life. In certain embodiments, the composition can be administered within the first 2 weeks of life and until the 12th week of life. In certain aspects, the composition can be administered to an infant aged 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 month old or less. The composition can be administered to an infant aged 12 months or less or 3 months or less. [00065] The infant can be breastfed, formula fed, or a combination thereof. Thus, in certain embodiments, the infant can derive at least some of its sustenance from human breastmilk. The infant can either nurse or the breastmilk can be expressed (e.g., pumped or hand-expressed) and given to the infant. The breastfed infant can be at least about 50%, 60%, 75%, 80%, 90% or 95% breastfed. The remainder of the infant’s sustenance can be derived from infant formula or other food. Alternatively, the breastfed infant can be exclusively breastfed and not receive infant formula. Any caloric contribution from other sources during the first 3 months of life, including medicines, the composition, or any medium used to deliver the composition is considered negligible. In certain embodiments, the infant can be exclusively formula fed. * * * [00066] While systems and methods have been described in connection with the various embodiments of the description, it will be appreciated by those skilled in the art that changes could be made to the embodiments without departing from the broad inventive concept thereof. It is understood, therefore, that this disclosure is not limited to the particular embodiments disclosed, and
CONSJCO6209WOPCT1 it is intended to cover modifications within the spirit and scope of the present disclosure as defined by the claims. [00067] It is to be appreciated that certain features of the invention which are, for clarity, described herein in the context of separate embodiments, may also be provided in combination in a single embodiment. That is, unless obviously incompatible or specifically excluded, each individual embodiment is deemed to be combinable with any other embodiment(s) and such a combination is considered to be another embodiment. Conversely, various features of the invention that are, for brevity, described in the context of a single embodiment, may also be provided separately or in any sub-combination. Finally, while an embodiment may be described as part of a series of steps or part of a more general structure, each said step may also be considered an independent embodiment in itself, combinable with others. [00068] It should be understood that the steps of the exemplary methods set forth herein are not necessarily required to be performed in the order described, and the order of the steps of such methods should be understood to be merely exemplary. Likewise, additional steps may be included in such methods, and certain steps may be omitted or combined, in methods consistent with various embodiments of the present invention. Although the elements in the following method claims, if any, are recited in a particular sequence with corresponding labeling, unless the claim recitations otherwise imply a particular sequence for implementing some or all of those elements, those elements are not necessarily intended to be limited to being implemented in that particular sequence. [00069] It is understood that the examples and embodiments described herein are for illustrative purposes only, and that changes could be made to the embodiments described above without departing from the broad inventive concept thereof. It is understood, therefore, that this invention is not limited to the particular embodiments disclosed, but it is intended to cover modifications within the spirit and scope of the invention as defined by the appended claims.
Claims
CONSJCO6209WOPCT1 CLAIMS 1. A method of preventing, delaying or ameliorating atopic disease in an infant, the method comprising administering a composition comprising an effective amount of a Bifidobacterium and at least one glycan to the infant. 2. The method of claim 1, wherein the Bifidobacterium is from the group B. longum. 3. The method of claims 1 or 2, wherein the Bifidobacterium is a B. longum subspecies infantis. 4. The method of claims 1-3, wherein about 5 billion CFU to about 10 billion CFU of the Bifidobacterium is administered to the infant. 5. The method of any of claims 1-4, wherein the at least one glycan includes a plant-based glycan. 6. The method of any of claims 1-5, wherein the at least one glycan includes an asparagine-linked glycan (N-glycan). 7. The method of any of claims 1-6, wherein the at least one glycan is derived from peanut. 8. The method of any of claims 1-7, wherein the at least one glycan is in the form of a powder. 9. The method of any of claims 1-8, wherein the infant is breastfed, formula fed, or a combination thereof. 10. The method of any of claims 1-9, wherein the infant is about 12 months old or less. 11. The method of claim 9, wherein the infant is about 6 months old or less. 12. The method of any of claims 1-11, wherein the composition is first administered to the infant within the first two weeks of life. 13. The method of any of claims 1-12, wherein the composition is administered daily. 14. The method of any of claims 1-13, wherein the atopic disease is atopic dermatitis, food allergy, allergic rhinitis, asthma, or combinations thereof.
CONSJCO6209WOPCT1 15. The method of any of claims 1-14, wherein the Bifidobacterium express carbohydrate active enzymes. 16. A method of preventing, delaying or ameliorating atopic disease in an infant, the method comprising administering to the mother of the infant a composition comprising an effective amount of a Bifidobacterium and at least one glycan during gestation of the infant. 17. The method of claim 16, wherein the Bifidobacterium is from the group B. longum. 18. The method of claims 16 or 17, wherein the Bifidobacterium is a B. longum subspecies infantis. 19. The method of claims 16-18, wherein about 5 billion CFU to about 10 billion CFU of the Bifidobacterium is administered to the infant. 20. The method of any of claims 16-19, wherein the at least one glycan includes a plant-based glycan. 21. The method of any of claims 16-20, wherein the at least one glycan includes an asparagine- linked glycan (N-glycan). 22. The method of any of claims 16-21, wherein the at least one glycan is derived from peanut. 23. The method of any of claims 16-22, wherein the at least one glycan is in the form of a powder. 24. The method of any of claims 16-23, wherein the composition is administered daily. 25. The method of any of claims 16-24, wherein the atopic disease is atopic dermatitis, food allergy, allergic rhinitis, asthma, or combinations thereof. 26. A composition comprising Bifidobacterium and at least one glycan derived from peanut. 27. The composition of claim 26, wherein the composition is in the form of a powder. 28. The composition of claim 26 or 27, wherein the Bifidobacterium is from the group B. longum.
CONSJCO6209WOPCT1 29. The composition of any of claims 26-29, wherein the Bifidobacterium is a B. longum subspecies infantis.
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2022112927A1 (en) * | 2020-11-24 | 2022-06-02 | Johnson & Johnson Consumer Inc. | Methods of preventing, delaying or ameliorating atopic diseases |
WO2023137381A2 (en) * | 2022-01-12 | 2023-07-20 | Washington University | Bifidobacterium infantis formulations |
WO2024008851A1 (en) * | 2022-07-08 | 2024-01-11 | Société des Produits Nestlé S.A. | Uses of bifidobacterium longum transitional microorganism |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2022112927A1 (en) * | 2020-11-24 | 2022-06-02 | Johnson & Johnson Consumer Inc. | Methods of preventing, delaying or ameliorating atopic diseases |
WO2023137381A2 (en) * | 2022-01-12 | 2023-07-20 | Washington University | Bifidobacterium infantis formulations |
WO2024008851A1 (en) * | 2022-07-08 | 2024-01-11 | Société des Produits Nestlé S.A. | Uses of bifidobacterium longum transitional microorganism |
Non-Patent Citations (1)
Title |
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KELLY SANDRA M. ET AL: "Plant Glycan Metabolism by Bifidobacteria", FRONTIERS IN MICROBIOLOGY, vol. 12, 4 February 2021 (2021-02-04), Lausanne, XP093132530, ISSN: 1664-302X, Retrieved from the Internet <URL:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889515/pdf/fmicb-12-609418.pdf> DOI: 10.3389/fmicb.2021.609418 * |
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