METHODS OF PROBIOTIC TREATMENT TO IMPROVE HUMAN HEALTH
Synbiotic compositions including both a prebiotic component and a probiotic component are provided. The prebiotic component includes at least one punicalagin, and the probiotic component includes a rationally defined and assembled consortium of microbial strains. Delivery capsules for oral administration of the synbiotic compositions and methods of using the synbiotic compositions to treat disease are also provided.
1 . A method for treating a disease in a human subject, comprising administering to the subject a therapeutically effective amount of a synbiotic composition, the synbiotic composition comprising:
a prebiotic component, comprising at least one compound that can be converted, by a microbial strain present in the healthy human gut microbiota, into a bioactive metabolite; and
a probiotic component, comprising a consortium of microbial strains, the consortium comprising at least two of:
(i) one or more digestive outcome-, gastrointestinal outcome-, or gut barrier function-improving microbial strains selected from the group consisting of Bifidobacterium breve SD-BR3-IT, Lactiplantibacillus plantarum SD-LP1-IT, Bifidobacterium longum SD-BB536-JP, Bifidobacterium infantis SD-M63-JP, Lacticaseibacillus rhamnosus HRVD113-US, Bifidobacterium lactis HRVD524-US (Bl-04), Bifidobacterium breve HRVD521-US, Lacticaseibacillus casei HRVD300-US, Bifidobacterium longum HRVD90b-US, Bifidobacterium lactis SD150-BE, Lacticaseibacillus rhamnosus SD-GG-BE, Limosilactobacillus reuteri RD830-FR, Lactobacillus crispatus SD-LCR01-IT, Limosilactobacillus fermentum SD-LF8-IT, Bifidobacterium lactis SD-BS5-IT, and Lacticaseibacillus rhamnosus SD-LR6-IT;
(ii) one or more dermatological outcome-improving microbial strains selected from the group consisting of Ligilactobacillus salivarius SD-LS1-IT, Bifidobacterium longum SD-CECT7347-SP, Lacticaseibacillus casei SD-CECT9104-SP, and Bifidobacterium lactis SD-CECT8145-SP;
(iii) one or more cardiovascular outcome-improving microbial strains selected from the group consisting of Lactiplantibacillus plantarum SD-LPLDL-UK and Bifidobacterium lactis SD-MB2409-IT; and
(iv) one or more micronutrient-synthesizing microbial strains selected from the group consisting of Limosilactobacillus reuteri SD-LRE2-IT and Bifidobacterium adolescentis SD-BA5-IT.
2 . The method of claim 1 , wherein the disease is selected from the group consisting of adrenal leukodystrophy, AGE-induced genome damage, Alexanders Disease, alopecia areata, Alper's Disease, Alzheimer's disease, amyotrophic lateral sclerosis, angina pectoris, arthritis, asthma, balo concentric sclerosis, Behcet's disease, bollus pemphigoid, Canavan disease, cardiac insufficiency including left ventricular insufficiency, central nervous system vasculitis, Charcott-Marie-Tooth Disease, childhood ataxia with central nervous system hypomyelination, chronic idiopathic peripheral neuropathy, chronic obstructive pulmonary disease, Crohn's disease, cutaneous lupus, dermatitis (contact, acute and chronic), diabetic retinopathy, graft versus host disease, granulomas, hepatitis C viral infection, herpes simplex viral infection, human immunodeficiency viral infection, Huntington's disease, irritable bowel disorder, ischemia, Krabbe Disease, lichen planus, macular degeneration, mitochondrial encephalomyopathy, monomelic amyotrophy, multiple sclerosis, myocardial infarction, neurodegeneration with brain iron accumulation, neuromyelitis optica, neurosarcoidosis, NF-κB mediated diseases, optic neuritis, pareneoplastic syndromes, Parkinson's disease, Pelizaeus-Merzbacher disease, pemphigus, primary lateral sclerosis, progressive supranuclear palsy, psoriasis, pyoderma gangrenosum, reperfusion injury, retinopathia pigmentosa, sarcoidosis, Schilders Disease, subacute necrotizing myelopathy, susac syndrome, transplantation rejection, transverse myelitis, a tumor, ulcerative colitis, and Zellweger's syndrome.
3 . The method of claim 1 , wherein the disease is a gastroenterological or infectious disease.
4 . The method of claim 3 , wherein the disease is selected from the group consisting of irritable bowel syndrome, COVID-19, and constipation.
5 . The method of claim 3 , wherein the disease is alcohol- or antibiotic-induced dysbiosis of the subject's gut microbiota.
6 . The method of claim 1 , wherein the synbiotic composition is administered as an ingestible formulation.
7 . The method of claim 6 , wherein the ingestible formulation is in the form of a swallowable capsule.
8 . The method of claim 7 , wherein the capsule comprises the prebiotic component in an amount of from about 1 mg to about 400 mg, or from about 25 mg to about 375 mg, or from about 50 mg to about 350 mg, or from about 75 mg to about 325 mg, or from about 100 mg to about 300 mg, or from about 125 mg to about 275 mg, or from about 150 mg to about 250 mg, or from about 175 mg to about 225 mg, or about 200 mg.
9 . The method of claim 7 , wherein the capsule comprises the consortium of microbial strains in an amount of from about 62.5 million AFU to about 312.5 billion AFU, from about 625 million AFU to about 250 billion AFU, from about 1.25 billion AFU to about 125 billion AFU, from about 6.25 billion AFU to about 62.5 billion AFU, from about 12.5 billion AFU to about 50 billion AFU, from about 18.75 billion AFU to about 37.5 billion, or from about 25 billion AFU to about 31.25 billion AFU.
10 . The method of claim 7 , wherein a dose of the synbiotic composition is administered at least once per day, wherein a dose comprises two swallowable capsules.
11 . The method of claim 7 , wherein the capsule further comprises at least one pharmaceutically acceptable vehicle.
12 . The method of claim 7 , wherein the swallowable capsule comprises:
an inner capsule, comprising the probiotic component; and
an outer capsule, surrounding and enclosing the inner capsule, comprising the prebiotic component,
wherein the outer capsule is configured to be substantially completely destroyed or dissolved after three hours in the environment of the human stomach and small intestine,
wherein the inner and outer capsules are configured such that a proportion of cells in the consortium of microbial strains that remain viable after three hours in the environment of the human stomach and small intestine is at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%, and
wherein the inner capsule is configured, upon entry into the colon of a human subject to whom the swallowable capsule is administered, to release at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% of viable cells of the consortium of microbial strains into the colon.
13 . The method of claim 1 , wherein the synbiotic composition is administered at least once per day for at least about 7 days.
14 . The method of claim 1 , wherein the at least one compound that can be converted, by a microbial strain present in the healthy human gut microbiota, into a bioactive metabolite comprises at least one punicalagin.
15 . The method of claim 14 , wherein the at least one punicalagin is derived or extracted from at least one pomegranate.
16 . The method of claim 15 , wherein the prebiotic component further comprises at least one additional compound derived or extracted from at least one pomegranate.
17 . The method of claim 15 , wherein the prebiotic component consists essentially of a polyphenolic pomegranate derivative or extract comprising the at least one punicalagin.
18 . The method of claim 14 , wherein the at least one punicalagin is capable of being metabolized, by at least one bacterial strain known to inhabit the human gastrointestinal tract, into a urolithin.
19 . The method of claim 18 , wherein the urolithin is urolithin-A.
20 . The method of claim 14 , wherein the at least one punicalagin is capable of being metabolized, by at least one microbial strain of the consortium of the probiotic component, into a urolithin.
21 . The method of claim 20 , wherein the urolithin is urolithin-A.
22 . The method of claim 1 , wherein the consortium comprises at least three of (i) through (iv).
23 . The method of claim 22 , wherein the consortium comprises all four of (i) through (iv).
24 . The method of claim 1 , wherein the consortium comprises at least two of the digestive outcome-, gastrointestinal outcome-, or gut barrier function-improving microbial strains of (i).
25 . The method of claim 1 , wherein the consortium comprises all of the digestive outcome-, gastrointestinal outcome-, or gut barrier function-improving microbial strains of (i), all of the dermatological outcome-improving microbial strains of (ii), all of the cardiovascular outcome-improving strains of (iii), and all of the micronutrient-synthesizing strains of (iv).
26 . The method of claim 25 , wherein the consortium consists essentially of all of the digestive outcome-, gastrointestinal outcome-, or gut barrier function-improving microbial strains of (i), all of the dermatological outcome-improving microbial strains of (ii), all of the cardiovascular outcome-improving strains of (iii), and all of the micronutrient-synthesizing strains of (iv).