Probiotic formulations and methods for use
Provided herein are compositions comprising a biocompatible microsphere, a biofilm-generating probiotic bacterium, a prebiotic, and/or a prebiofilmic. Methods for preparing and formulating the compositions and methods for treating or preventing a disease using the compositions are also provided.
1. A composition comprising a biocompatible microsphere, a prebiotic, and a biofilm-generating probiotic bacterium that releases a DNABII protein, wherein the prebiotic comprises an effective amount of a nutritional supplementation for the probiotic bacterium to support the formation of a biofilm, and wherein the prebiotic diffuses from within the microsphere.
2. The composition of claim 1 , further comprising a biofilm formed on the surface of the microsphere and optionally a prebiofilmic.
3. The composition of claim 2 , wherein the prebiofilmic comprises an agent that supports biofilm formation and durability.
4. The composition of claim 3 , wherein the prebiofilmic is a DNA binding polypeptide or protein and/or a DNABII polypeptide or protein.
5. The composition of claim 1 , wherein the prebiotic comprises a water-soluble carbohydrate, wherein the water-soluble carbohydrate comprises one or more of inulin, oligofructose, fructo-oligosaccharide, galacto-oligosaccharide, glucose, maltose, maltodextrins, polydextrose, sucrose, fructose, lactose, isomaltulose, polyols, glycerol, and combination thereof.
6. The composition of claim 1 , further comprising a pharmaceutically acceptable carrier or a biocompatible scaffold.
7. The composition of claim 1 , wherein the probiotic bacterium is one or more of L. acidophilus, L. crispatus, L. gasseri, group L. delbrueckii, L. salivarius, L. casei, L. paracasei, L. plantarum, L. rhamnosus, L. reuteri , L. brevis, L. buchneri, L. fermentum, L. rhamnosus, B. adolescentis, B. angulation, B. bifidum, B. breve, B. catenulatum, B. infantis, B. lactis, B. longum, B. pseudocatenulatum, S. thermophiles , and a combination thereof.
8. The composition of claim 7 , wherein the probiotic bacterium is Lactobacillus reuteri (“ L. reuteri ”).
9. The composition of claim 1 , wherein the probiotic bacterium provides one or more of supporting anti-bacterial immunity, enhancing or supporting the gastrointestinal barrier, treating dysbiosis, treating or preventing gut pathogenesis, supporting gastrointestinal health, a chronic and/or a recurrent disease that is caused by pathogenic bacteria displacing healthy bacteria or antagonizing disease-related bacterial infections.
10. The composition of claim 1 , wherein the probiotic bacterium prevents pathogen colonization and/or limits excessive inflammatory responses by down-regulating cytokine and chemokine production.
11. The composition of claim 1 , wherein the biocompatible microsphere comprises one or more of a biodegradable polymer, a non-biodegradable polymer, a metal, or a combination thereof.
12. The composition of claim 11 , wherein the microsphere comprises a core selected from a solid core or a hollow core and optionally wherein the prebiotic is encapsulated within the hollow core.
13. The composition of claim 1 , further comprising an agent, wherein the agent is selective against a pathogen.
14. The composition of claim 1 , wherein the microsphere is a biodegradable polymer.
15. The composition of claim 14 , wherein the biodegradable polymer is one or more of Sephadex, Sephadex G-25, poly(lactic-co-glycolic acid)(“PLGA”); polycaprolactone (“PLC”); chitosan; gelatin; DNA hydrogen; acetalated dextran; poly(lactide); poly(glycolide); poly(lactide-co-glycolide); poly(lactic acid); poly(glycolic acid); poly(lactic acid-co-glycolic acid); poly(lactide)/poly(ethylene glycol) copolymers; poly(glycolide)/poly(ethylene glycol) copolymer; poly(lactide-co-glycolide)/poly(ethylene glycol) copolymers; poly(lactic acid)/poly(ethylene glycol) copolymer; poly(glycolic acid)/poly(ethylene glycol) copolymer; poly(lactic acid-co-glycolic acid)/poly(ethylene glycol) copolymer; poly(caprolactone); poly(caprolactone)/poly(ethylene glycol) copolymer; poly(orthoester); poly(phosphazene); poly(hydroxybutyrate); poly(hydroxybutyrate); poly(lactide-co-caprolactone); polycarbonate; polyesteramide; polyanhidride; poly(dioxanone); poly(alkylene alkylate); polyethylene glycol/polyorthoester copolymer; polyurethane; poly(amino acid); polyetherester; polyacetal; polycyanoacrylate; poly(oxyethylene)/poly(oxypropylene) copolymer; and a combination thereof.
16. The composition of claim 1 , wherein the microsphere comprises a non-biodegradable polymer.
17. The composition of claim 16 , wherein the non-biodegradable polymer is one or more of poly(ethylene vinyl acetate), poly(vinyl acetate), silicone polymers, polyurethanes, polysaccharides such as a cellulosic polymers and cellulose derivatives, acyl substituted cellulose acetates and derivatives thereof, copolymers of poly(ethylene glycol), poly(butylene terephthalate), polystyrenes, polyvinyl chloride, polyvinyl fluoride, poly(vinyl imidazole), chlorosulphonated polyolefins, polyethylene oxide, and copolymers and blends thereof.
18. The composition of claim 1 , wherein the microsphere comprises a metal.
19. The composition of claim 18 , wherein the metal comprises one or more of cobalt, chromium, gold, nickel, platinum, stainless steel, titanium, tantalum, nickel-titanium, and alloys and combinations thereof.
20. A method for treating a disease suitably treated by a biofilm in a subject in need thereof, comprising administering to the subject an effective amount of the composition of claim 1 or 2 .
21. The method of claim 20 , wherein the diseases comprises one or more of inflammatory bowel disease (IBD), colitis, enteric infectious disease, diarrheal illness, vaginosis, necrotizing enterocolitis (NEC), wound, burns, psoriasis, dermatitis, tooth decay, periodontitis, sinusitis, infection-induced colitis, traveler's diarrhea, psychological stress, psychological disorders, or any of chronic or recurrent disease that is caused by pathogenic bacteria displacing healthy bacteria.
22. The composition of claim 1 or 2 , wherein the microsphere is comprised of a biodegradable polymer, the probiotic bacterium is L. reuteri , and the prebiotic comprises maltose.
23. A method for treating a disease suitably treated by a biofilm in a subject in need thereof, comprising administering to the subject an effective amount of the composition of claim 22 .
24. A composition consisting essentially of a biocompatible microsphere, a prebiotic, and a probiotic bacterium that releases a DNABII protein, wherein the prebiotic comprises a nutritional supplementation for the probiotic bacterium, and the probiotic bacterium and the prebiotic are provided in an amount effective to support the formation of a biofilm adhered to the surface of the microsphere, and wherein the prebiotic diffuses from within the microsphere.
25. A composition consisting essentially of 1) a biocompatible microsphere, 2) a probiotic bacterium that releases a DNABII protein, 3) a prebiotic, wherein the prebiotic comprises a nutritional supplementation for the probiotic bacterium, and the probiotic bacterium and the prebiotic are provided in an amount effective to support the formation of a biofilm on the surface of the microsphere, and 4) a biofilm adhered to the surface of the microsphere, wherein the prebiotic diffuses from within the microsphere.
26. A method for treating a disease suitably treated by a biofilm in a subject in need thereof, comprising administering to the subject an effective amount of the composition of claim 24 or 25 .
27. The composition of any one of claim 1 , 24 or 25 , wherein the prebiotic diffuses slowly from the microsphere.