Use of L. reuteri for recovery of microbiota dysbiosis in early life
Inventors
Garcia-Rodenas, Clara Lucia • Berger, Bernard • Ngom-Bru, Catherine • LePage, Melissa • NEVILLE, Tara
Assignees
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Publication Number
US-11701397-B2
Publication Date
2023-07-18
Expiration Date
Abstract
The invention concerns Lactobacillus reuteri for use in the prevention or treatment of microbiota dysbiosis, in particular, decreased levels of Actinobacteria and increased levels of Proteobacteria, in young mammals and in the prevention or treatment of disorders associated therewith. The microbiota dysbiosis may have been cause by numerous factors including being born by caesarean section, exposure to antibiotics in utero or after birth, or, parenteral feeding, hospitalizing, psychological stress or by gastrointestinal dysfunctions. The disorders that may be treated or prevented by preventing or treating microbiota dysbiosis include propensity to infection, allergy, type I diabetes mellitus, insulin resistance, type 2 diabetes, celiac disease, peripheral and central adiposity, obesity, necrotizing enterocolitis, inflammatory bowel disease, such as Crohn's disease and ulcerative colitis, and functional gastrointestinal disorders such as IBS, functional diarrhea, functional constipation, recurrent abdominal pain, and dyspepsia.
Core Innovation
The document describes administering Lactobacillus reuteri to young humans to prevent or treat microbiota dysbiosis and related disorders. Microbiota dysbiosis is characterized by decreased Actinobacteria, including Bifidobacterium, and increased Proteobacteria, with associated disorders including infections and metabolic and gastrointestinal diseases.
The background identifies dysbiosis-inducing factors including C-section, in utero and/or postnatal antibiotics, parenteral feeding, hospitalization, psychological stress, and gastrointestinal dysfunctions. The document links these factors to target disorders including insulin resistance, type 2 diabetes, type 1 diabetes, allergy/atopy, celiac disease, necrotizing enterocolitis, inflammatory bowel disease, functional gastrointestinal disorders, dyspepsia, and adiposity/obesity.
For C-section infants, the document reports that a Lactobacillus reuteri-containing formula shifts the microbiota toward a vaginal-delivery profile. It states that Actinobacteria are restored and Proteobacteria are reduced at about two weeks, with a complete recovery effect by about four months, and discusses Lactobacillus reuteri DSM 17938 and delivery routes, including direct to the infant or via lactating/expectant mother.
Claims Coverage
The independent claim provides a method for treating or reducing the risk of selected metabolic disorders in a young human up to three years old associated with microbiota dysbiosis, based on administering Lactobacillus reuteri effective to treat the microbiota dysbiosis. The claim set includes six inventive features.
Treating or reducing risk of selected disorders associated with microbiota dysbiosis in young humans
A method for treatment or reducing a risk of one or more disorders selected from insulin resistance, type 2 diabetes, peripheral and central adiposity, and obesity, wherein the disorders are associated with microbiota dysbiosis occurring in a young human aged up to three years and occur in the young human or later in life.
Administering Lactobacillus reuteri effective to treat microbiota dysbiosis
Administering Lactobacillus reuteri to the young human, wherein the young human is suffering from microbiota dysbiosis and the administering is effective to treat the microbiota dysbiosis.
Selecting and dosing according to infant/toddler or fetus/breast-fed infant or expectant/lactating mother
Selecting a young human as either an infant or a toddler and administering Lactobacillus reuteri as a daily dose of 1×10^3 to 1×10^12 cfu; and/or selecting a young human as a fetus, breast-fed infant, or an infant and administering Lactobacillus reuteri to an expectant mother, lactating mother, or the infant in a composition containing between 1×10^3 and 1×10^12 cfu/g of dry composition.
Direct versus indirect administration via lactating mother
Administering Lactobacillus reuteri to a young human either directly or indirectly via administration to the lactating mother.
Using Lactobacillus reuteri DSM 17938
Performing the method using Lactobacillus reuteri identified as Lactobacillus reuteri DSM 17938.
Optionally adding additional probiotic strains by named identifiers
Specifying additional probiotics chosen from Bifidobacterium longum BB536 (ATCC BAA-999), Lactobacillus rhamnosus (CGMCC 1.3724), Bifidobacterium lactis (NCC2818), or mixtures thereof.
Overall, the claims center on using Lactobacillus reuteri administration to treat microbiota dysbiosis in young humans associated with selected metabolic disorders, with coverage expanded by subpopulation selection, administration modality, strain identity, and optional additional probiotic strains.
Stated Advantages
Restores Actinobacteria and reduces Proteobacteria in C-section infants receiving a Lactobacillus reuteri-containing formula.
Achieves a complete recovery effect by about four months in C-section infants.
Documented Applications
Prevention or treatment of microbiota dysbiosis in young mammals or young humans, including early-life dysbiosis associated with C-section and antibiotics, and targeting insulin resistance, type 2 diabetes, adiposity/obesity, allergic/atopic conditions, celiac disease, necrotizing enterocolitis, inflammatory bowel disease, and functional gastrointestinal disorders.
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