PREBIOTIC FORMULATIONS

• US 20180000878A1
• Filed: 07/13/2017
• Published: 01/04/2018
• Est. Priority Date: 03/06/2014
• Status: Active Grant

• Current Assignee: Ohio State Innovation Foundation (Ohio State University)
• Original Assignee: Research Institute at Nationwide Children's Hospital
• Inventors: Goodman, Steven D., Bakaletz, Lauren O., Bailey, Michael, Besner, Gail
• Granted Patent: US 10,624,934 B2
• Time in Patent Office: Days
• CPC Class Codes: A01N 63/20 Bacteria; Substances produced thereby or obtained therefrom
• CPC Class Codes: A01N 63/22 Bacillus
• CPC Class Codes: A01N 63/23 B. thuringiensis
• CPC Class Codes: A01N 63/27 Pseudomonas
• CPC Class Codes: A23L 33/135 Bacteria or derivatives thereof, e.g. probiotics
• CPC Class Codes: A23L 33/195 Proteins from microorganisms
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A23V 2200/3202 Prebiotics, ingredients fermented in the gastrointestinal tract by beneficial microflora
• CPC Class Codes: A23V 2200/3204 Probiotics, living bacteria to be ingested for action in the digestive tract
• CPC Class Codes: A61K 35/741 Probiotics probiotic yeast, e.g. saccharomyces A61K36/06
• CPC Class Codes: A61K 35/747 Lactobacilli, e.g. L. acidophilus or L. brevis
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 9/0031 Rectum, anus
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/1658 Proteins, e.g. albumin, gelatin
• CPC Class Codes: A61K 9/50 Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals A61K9/2081 takes precedence; particles with a single coating comprising drug A61K9/167

Abstract

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.

Claims

1. A composition comprising a microsphere, a biofilm-generating probiotic bacterium and a prebiotic, wherein the prebiotic comprises a nutritional supplementation for the probiotic bacterium.

2. The composition of claim 1, wherein the microsphere further comprises a partial or complete biofilm coating on the external surface of the microsphere.

3. The composition of claim 1, wherein the biocompatible microsphere comprises a material selected from the group of:

a biodegradable polymer, a non-degradable polymer, a metal, and wherein the diameter of the microsphere is from about 0.5 microns to about 1000 microns.

4. The composition of claim 1, further comprising one or more of:

a prebiofilmic, a therapeutic drug or agent, a chemical reductant, a molecule that promotes adsorption, a molecule that supports absorption.

5. The composition of claim 4, wherein the prebiofilmic comprises an agent that supports biofilm formation and durability.

6. The composition of claim 5, wherein the prebiofilmic is a DNA binding polypeptide or protein and/or a DNABII polypeptide or protein or an equivalent of each thereof.

7. The composition of claim 6, wherein the prebiotic comprises a water-soluble carbohydrate, inulin, oligosaccharides, oligofructose, fructo-oligosaccharide, galacto-oligosaccharide, glucose, starch, maltose, maltodextrins, polydextrose, amylose, sucrose, fructose, lactose, isomaltulose, polyols, glycerol, carbonate, thiamine, choline, histidine, trehalos, nitrogen, sodium nitrate, ammonium nitrate, phosphorus, phosphate salts, hydroxyapatite, potassium, potash, sulfur, homopolysaccharide, heteropolysaccharide, cellulose, chitin, vitamins, and combination thereof.

8. The composition of claim 1, further comprising a pharmaceutically acceptable carrier or a biocompatible scaffold.

9. 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, Pseudomonas fluorescens, P. protegens, P. brassicacearum, P. aeruginosa;

Azospirillum. brabrasilense, A. lipferum, A. halopraeferens, A. irakense;

Acetobacter diazotrophicus;

Herbaspirillum seropedicae;

Bacillus subtilis, Pseudomonas stutzeri, fluorescens, P. putida, P. cepacian, P. vesicularis, P. paucimobilis;

Bacillus cereus, B. thuringiensis, B. sphaericus;

Shewanella oneidensis;

Geobacter bemidjiensis, G. metallireducens, G. sulfurreducens, G. uraniireducens, G. lovleyi;

Serratia marcescens, Desulfovibrio vulgaris, D. desulfuricans, Dechloromonas aromatic, Deinococcus radiodurans, Methylibium petroleiphilum, Alcanivorax borkumensis, Archaeglobus fulgidus, Haloferax sp., Halobacterium sp., and combinations thereof.

10. The composition of claim 1, wherein the probiotic bacterium provides one or more of supporting anti-bacterial immunity, correcting dysbiosis, enhancing or supporting the gastrointestinal barrier, supporting or enhancing gastrointestinal motility, localized release of antibiotic compositions, or antagonizing disease-related bacterial infections.

11. 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.

12. The composition of claim 1, wherein the microsphere comprises a solid core or a hollow core.

13. The composition of claim 1, wherein the prebiotic is encapsulated within the hollow core.

14. The composition of claim 1, further comprising an agent, wherein the agent is selective against a pathogen.

15. The composition of claim 1, wherein a complimentary agent is coated on the surface of the microsphere and/or encapsulated within the hollow core.

16. The composition of claim 1, wherein the microsphere comprises a metal selected from one or more of cobalt, chromium, gold, nickel, platinum, stainless steel, titanium, tantalum, nickel-titanium, an alloy, and combinations thereof.

17. The composition of claim 1, wherein the microsphere comprises a biodegradable polymer selected from one or more dextran;

dextranomer;

poly(lactic-co-glycolic acid) or PLGA;

polycaprolactone or 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;

Sephadex®

copolymers and/or a combination thereof.

18. The composition of claim 1, wherein the microsphere comprises a non-biodegradable polymer selected from 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) and poly(butylene terephthalate), polystyrenes, polyvinyl chloride, polyvinyl fluoride, poly(vinyl imidazole), chorosulphonated polyolefins, polyethylene oxide, and copolymers and blends thereof.

19. The composition of claim 1, wherein the microsphere comprises a polymer selected from 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.

20. The composition of claim 1, wherein the microsphere comprises a non-biodegradable polymer selected from 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), chorosulphonated polyolefins, polyethylene oxide, and copolymers and blends thereof.

21. The composition of claim 1 or 2, wherein:

the probiotic bacteria comprises L. reuteri;

the prebiotic comprises glycerol or histadine.

22. The composition of claim 21, wherein the L. reuteri produces glucosyltransferase (GFT).

23. The composition of claim 21, wherein the microsphere comprises dextran or dextranomer.

26. The method of claim 1, further comprising admixing one or more of:

a prebiofilmic, a therapeutic drug or agent, a chemical reductant, a molecule that promotes adsorption, a molecule that supports absorption.

49. A method for one or more of:

promoting health, maintaining gut homeostasis, treating disease, or preventing a disease, each suitably treated by the formation or enhancement of a biofilm in a subject in need thereof, comprising administering to the subject an effective amount of the composition of claim 1 or 2, and optionally wherein the surface of the microsphere is porous and/or semi-permeable and the prebiotic is released by diffusion or the microsphere slowly degrades causing leaks and diffusion from the microsphere.

50. The method of claim 49, wherein the disease comprises one or more of inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), dysbiosis, 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.

52. A method of administering a probiotic to a subject comprising administering a dose of a composition of claim 1 or 2 to a subject, thereby administering the probiotic.

53. The method of claim 52, wherein the composition is administered to provide from about 1×

10⁷ to about 1×

10⁹ CFU/ml of the biofilm-generating probiotic bacterium.

54. The method of claim 52, wherein the composition is administered at about 6, 12, 18, 24, 36, 48, and 72 hours.

55. The method of claim 52, wherein the composition is administered in a single dose.

56. A method for treating a plant, comprising topically applying to the plant the composition of claim 1 or irrigating the plant with the composition of claim 1 or 2.

57. A method for treating a plant, comprising irrigating admixing the composition of claim 1 with water applying to the plant the composition of claim 1.

58. A method or treating an industrial environment, comprising contacting the environment with the composition of claim 1.

59. A formulation comprising the composition of claim 1 or 2, wherein the composition is formulated in a dosage form selected from the group consisting of:

suppository, within a biocompatible scaffold, powder, liquid, capsule, chewable tablet, swallowable tablet, buccal tablet, troche, lozenge, soft chew, solution, suspension, spray, tincture, decoction, infusion, and combinations thereof.

60. A kit comprising the composition of claim 1 or 2, and instructions for use.

71. The method of claim 49, wherein release of the prebiotic is regulated by varying microsphere size (smaller microspheres release faster) or by altering the viscosity of the prebiotic (i.e. the higher the viscosity the slower the release).

24. A method for preparing a composition comprising admixing a microsphere with a biofilm-generating probiotic bacterium and a prebiotic and optionally, in a culture comprising a biofilm.

25. The method of claim 24, further comprising admixing a prebiofilmic.

27. The method of claim 25, wherein the prebiofilmic comprises an agent that supports biofilm formation and durability.

28. The method of claim 25, wherein the prebiofilmic is a DNA binding polypeptide or protein and/or a DNABII polypeptide or protein or an equivalent of each thereof.

29. The method of claim 25, wherein the prebiotic comprises a water-soluble carbohydrate, inulin, oligosaccharides, oligofructose, fructo-oligosaccharide, galacto-oligosaccharide, glucose, starch, maltose, maltodextrins, polydextrose, amylose, sucrose, fructose, lactose, isomaltulose, polyols, glycerol, carbonate, thiamine, choline, histidine, trehalos, nitrogen, sodium nitrate, ammonium nitrate, phosphorus, phosphate salts, hydroxyapatite, potassium, potash, sulfur, homopolysaccharide, heteropolysaccharide, cellulose, chitin, vitamins, and combination thereof.

30. The method of claim 24, 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, Pseudomonas fluorescens, P. protegens, P. brassicacearum, P. aeruginosa;

Azospirillum. brabrasilense, A. lipferum, A. halopraeferens, A. irakense;

Acetobacter diazotrophicus;

Herbaspirillum seropedicae;

Bacillus subtilis, Pseudomonas stutzeri, fluorescens, P. putida, P. cepacian, P. vesicularis, P. paucimobilis;

Bacillus cereus, B. thuringiensis, B. sphaericus;

Shewanella oneidensis;

Geobacter bemidjiensis, G. metallireducens, G. sulfurreducens, G. uraniireducens, G. lovleyi;

Serratia marcescens, Desulfovibrio vulgaris, D. desulfuricans, Dechloromonas aromatic, Deinococcus radiodurans, Methylibium petroleiphilum, Alcanivorax borkumensis, Archaeglobus fulgidus, Haloferax sp., Halobacterium sp., and combinations thereof.

31. The method of claim 24, wherein the probiotic bacterium provides one or more of supporting anti-bacterial immunity, correcting dysbiosis, enhancing or supporting the gastrointestinal barrier, supporting or enhancing gastrointestinal motility, localized release of antibiotic compositions, or antagonizing disease-related bacterial infections.

32. The method of claim 24, wherein the probiotic bacterium prevents pathogen colonization and/or limits excessive inflammatory responses by down-regulating cytokine and chemokine production.

33. The method of claim 24, wherein the microsphere comprises a solid core.

34. The method of claim 24, wherein the microsphere comprises a hollow core.

35. The method of claim 24, further comprising admixing an agent, wherein the agent is selective against a pathogen.

36. The method of claim 24, further comprising coating the surface of the microsphere and/or encapsulated within the hollow core.

37. The method of claim 24, wherein the microsphere comprises a metal selected from one or more of cobalt, chromium, gold, nickel, platinum, stainless steel, titanium, tantalum, nickel-titanium, an alloy, and combinations thereof.

38. The method of claim 24, wherein the microsphere comprises a biodegradable polymer selected from one or more of:

dextran;

dextranomer;

poly(lactic-co-glycolic acid) or PLGA;

polycaprolactone or 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;

Sephadex®

copolymers and/or a combination thereof.

39. The method of claim 24, wherein the microsphere comprises a non-biodegradable polymer selected from 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) and poly(butylene terephthalate), polystyrenes, polyvinyl chloride, polyvinyl fluoride, poly(vinyl imidazole), chorosulphonated polyolefins, polyethylene oxide, and copolymers and blends thereof.

40. The method of claim 24, wherein the microsphere comprises a polymer selected from 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.

41. The method of claim 24, wherein the microsphere comprises a non-biodegradable polymer selected from 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), chorosulphonated polyolefins, polyethylene oxide, and copolymers and blends thereof.

42. The method of claim 24, wherein the prebiotic comprises a water-soluble carbohydrate, which comprises one or more of inulin, oligofructose, fructo-oligosaccharide, galacto-oligosaccharide, glucose, maltose, maltodextrins, polydextrose, sucrose, fructose, lactose, isomaltulose, polyols, glycerol, and combinations thereof.

43. The method of claim 24, wherein the prebiotic comprises a water-soluble carbohydrate, inulin, oligosaccharides, oligofructose, fructo-oligosaccharide, galacto-oligosaccharide, glucose, starch, maltose, maltodextrins, polydextrose, amylose, sucrose, fructose, lactose, isomaltulose, polyols, glycerol, carbonate, thiamine, choline, histidine, trehalos, nitrogen, sodium nitrate, ammonium nitrate, phosphorus, phosphate salts, hydroxyapatite, potassium, potash, sulfur, homopolysaccharide, heteropolysaccharide, cellulose, chitin, vitamins, and combination thereof.

44. The method of claim 24, 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, Pseudomonas fluorescens, P. protegens, P. brassicacearum, P. aeruginosa;

Azospirillum. brabrasilense, A. lipferum, A. halopraeferens, A. irakense;

Acetobacter diazotrophicus;

Herbaspirillum seropedicae;

Bacillus subtilis, Pseudomonas stutzeri, fluorescens, P. putida, P. cepacian, P. vesicularis, P. paucimobilis;

Bacillus cereus, B. thuringiensis, B. sphaericus;

Shewanella oneidensis;

Geobacter bemidjiensis, G. metallireducens, G. sulfurreducens, G. uraniireducens, G. lovleyi;

Serratia marcescens, Desulfovibrio vulgaris, D. desulfuricans, Dechloromonas aromatic, Deinococcus radiodurans, Methylibium petroleiphilum, Alcanivorax borkumensis, Archaeglobus fulgidus, Haloferax sp., Halobacterium sp., and combinations thereof.

45. The method of claim 24, wherein the probiotic bacterium comprises 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 combinations thereof.

46. The method of claim 24, wherein:

the probiotic bacteria comprises L. reuteri;

the prebiotic comprises glycerol or histadine.

47. The method of claim 46, wherein the L. reuteri produces glucosyltransferase (GTF).

48. The method of claim 46, wherein the microsphere comprises dextran or dextranomer.

51. The method of claim 46, wherein the disease is selected from the group of:

psychological disorders, such as depression or anxiety, enteric infectious disease, infection-induced colitis, traveler'"'"'s diarrhea, inflammatory bowel disease (IBD), colitis, diarrheal illness, vaginosis, wound, burns, psoriasis, dermatitis, tooth decay, periodontitis, sinusitis, or any of chronic and/or recurrent disease that is caused by pathogenic bacteria displacing healthy bacteria or nectrotizing enterocolitis (NEC), and to support anti-bacterial immunity, enhancing or supporting the gastrointestinal barrier, correcting or supporting dysbiotic gut flora (and even in the absence of diseases), disease or disorders involving intestinal dysmobility, enhancing or supporting the gastrointestinal mobility, or antagonizing disease-related bacterial infection;

vaginosis;

colitis or traveler'"'"'s diarrhea, peritonitis, post-operative ileus, irritable bowel syndrome (IBS), intestinal pseudo-obstruction, and/or constipationpsychological disorders, such as depression or anxiety, enteric infectious disease, infection-induced colitis, traveler'"'"'s diarrhea, inflammatory bowel disease (IBD), colitis, diarrheal illness, vaginosis, wound, burns, psoriasis, dermatitis, tooth decay, periodontitis, sinusitis, or any of chronic and/or recurrent disease that is caused by pathogenic bacteria displacing healthy bacteria or nectrotizing enterocolitis (NEC);

to support anti-bacterial immunity, enhancing or supporting the gastrointestinal barrier, or antagonizing disease-related bacterial infection;

vaginosis;

colitis or traveler'"'"'s diarrhea, peritonitis, post-operative ileus, irritable bowel syndrome, intestinal pseudo-obstruction, and constipation.

61. A composition comprising a PGLA-biocompatible microsphere, one or more biofilm-generating probiotic bacterium comprising at least Lactobacillus reuteri (“

L. reuteri”

), and a nutritional supplementation comprising one or more of sucrose, glycerol or histadine, in an amount to support the growth of the probiotic bacterium, and optionally wherein the microsphere is partially or wholly coated with a biofilm.

62. The composition of claim 61, further comprising an effective amount of HU or IHF polypeptide or protein.

63. The composition of claim 61, further comprising a pharmaceutically acceptable carrier or a biocompatible scaffold.

64. The composition of claim 61, wherein the microsphere has a diameter in the range of from about 0.5 microns to 75 microns.

65. A method for preparing the composition of claim 61, comprising admixing a PGLA-biocompatible microsphere with an effective amount of one or more biofilm-generating probiotic bacterium comprising at least Lactobacillus reuteri (“

L. reuteri”

), and a nutritional supplementation comprising one or more of sucrose or glycerol in an amount to support the growth of the probiotic bacterium.

66. The method of claim 65, further comprising admixing an effective amount of HU or IHF polypeptide or protein.

67. A method for treating a gastrointestinal disorder or supporting gastrointestinal health, comprising administering to a subject in need thereof an effective amount of the composition of claim 61, thereby treating the gastrointestinal disorder or supporting gastrointestinal health.

68. The method of claim 67, wherein the gastrointestinal disorder is one or more of infection-induced colitis, inflammatory bowel disease, dysbiosis, necrotizing enterocolitis (NEC) or traveler'"'"'s diarrhea.

69. The method of claim 67, wherein the composition is administered as a suppository formulation.

70. A kit comprising the composition of claim 61, and instructions for use.