Compositions and methods for improving skin health and for the treatment and prevention of diseases, disorders and conditions associated with pathogenic microbes

Abstract

Disclosed herein are compositions and methods for using human-derived Janthinobacterium lividum. Compositions improve skin health. Methods may include applying human-derived Janthinobacterium lividum over a host or host area, such as skin or mucosa, to minimize the presence of one or more microbes, maximize therapeutic effects, and/or improve health. A method to minimize a pathogenic microbe may include applying to a surface a composition including human-derived Janthinobacterium lividum and an acceptable carrier. Compositions and methods may include a prebiotic to maximize growth and/or metabolites. Compositions and methods may include human-derived Janthinobacterium lividum metabolites, such as violacein, prodigiosin, indole-3-carboxaldehyde, and lantibiotics, and/or other Postbiotics.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising human-derived  Janthinobacterium lividum  in an amount effective to treat, inhibit or prevent a disease, disorder, or condition associated with a pathogenic microorganism. 
     
     
         2 . The composition of  claim 1 , formulated for topical application to prevent, treat, or reduce a symptom of a disease of a mammalian subject arising from an infection with a pathogenic microorganism. 
     
     
         3 . The composition of  claim 1 , wherein the  Janthinobacterium lividum  comprises a nucleic acid sequence at least 95% identical to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7. 
     
     
         4 . The composition of  claim 1 , wherein the  Janthinobacterium lividum  comprises a nucleic acid sequence at least 99% identical to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7. 
     
     
         5 . The composition of  claim 1 , further comprising an additional isolated microbe. 
     
     
         6 . The composition of  claim 1 , further comprising a first additional isolated microbe and a second additional isolated microbe, wherein the first and second additional isolated microbes are independently selected from bacteria, virus, yeast, or fungus. 
     
     
         7 . The composition of  claim 1 , wherein the disease, disorder, or condition is associated with, but not limited to dermatophytes, and is selected from tinea barbae, tinea capitis, tinea corporis, tinea curis, tinea pedis, or onychomycosis; or the disease, disorder, or condition is associated with, but not limited to gram positive bacteria and  Staphylococcus , and is selected from atopic dermatitis, impetigo, skin infections and soft tissue infections. 
     
     
         8 . The composition of  claim 5 , wherein the additional isolated microbe comprises  Lactobacillus, Lactococcus  or  Propionibacterium.    
     
     
         9 . The composition of  claim 1 , further comprising an anti-fungal compound. 
     
     
         10 . The composition of  claim 9 , wherein the anti-fungal compound is present in the composition in a therapeutic amount. 
     
     
         11 . The composition of  claim 9 , wherein the anti-fungal compound is present in the composition in a sub-therapeutic amount. 
     
     
         12 . The composition of  claim 1 , further comprising an anti-bacterial compound. 
     
     
         13 . The composition of  claim 12 , wherein the anti-bacterial compound is present in the composition in a therapeutic amount. 
     
     
         14 . The composition of  claim 12 , wherein the anti-bacterial compound is present in the composition in a sub-therapeutic amount. 
     
     
         15 . The composition of  claim 1 , further comprising a prebiotic. 
     
     
         16 . The composition of  claim 15 , wherein the prebiotic is selected from one or more of an amino acid, biotin, glycerol, fructooligosaccharide, galactooligosaccharide, inulin, lactulose, mannan oligosaccharide, oligofructose-enriched inulin, oligofructose, oligodextrose, tagatose, trans-galactooligosaccharide, and xylooligosaccharide. 
     
     
         17 . The composition of  claim 1 , further comprising at least one postbiotic. 
     
     
         18 . The pharmaceutical composition of  claim 1 , wherein the diseases, disorder, or condition comprises a skin disease, disorder, or condition in a mammalian subject. 
     
     
         19 . The pharmaceutical composition of  claim 18 , wherein the mammalian subject is a human subject. 
     
     
         20 . The pharmaceutical composition of  claim 19 , wherein the pharmaceutical composition is administered in an amount effective to treat, inhibit, reduce a symptom of, or prevent the human skin disease, disorder, or condition. 
     
     
         21 . The pharmaceutical composition of  claim 19 , wherein the pharmaceutical composition is administered in an amount effective to inhibit the growth of a topical pathogenic microorganism present on or in a tissue of the human subject. 
     
     
         22 . The pharmaceutical composition of  claim 21 , wherein the topical pathogenic microorganism is a Dermatophyte. 
     
     
         23 . The pharmaceutical composition of  claim 22 , wherein the topical pathogenic microorganism is  Trichophyton mentagrophytes.    
     
     
         24 . The pharmaceutical composition of  claim 22 , wherein the topical pathogenic microorganism is  Trichophyton rubrum.    
     
     
         25 . The pharmaceutical composition of  claim 21 , wherein the topical pathogenic microorganism is a bacterium. 
     
     
         26 . The pharmaceutical composition of  claim 25 , wherein the bacterium is  Staphylococcus aureus.    
     
     
         27 . The pharmaceutical composition of  claim 1 , wherein the  Janthinobacterium lividum  are desiccated. 
     
     
         28 . The pharmaceutical composition of  claim 27 , wherein the  Janthinobacterium lividum  are at least 20% viable upon rehydration from desiccated conditions. 
     
     
         29 . The pharmaceutical composition of  claim 1 , wherein the composition is at least 30% viable at room temperature for at least thirty days. 
     
     
         30 . The pharmaceutical composition of  claim 1 , wherein the composition comprises a dried formulation of human-derived  Janthinobacterium lividum.    
     
     
         31 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition is formulated for topical administration to a human or non-human subject. 
     
     
         32 . The pharmaceutical composition of  claim 31 , wherein the pharmaceutical composition is formulated as a cream, gel, foam, ointment, powder or lotion. 
     
     
         33 . The pharmaceutical composition of  claim 31 , wherein the pharmaceutical composition is formulated as a liquid, tincture, spray, mister, or inhaler. 
     
     
         34 . The pharmaceutical composition of  claim 31 , wherein the composition is formulated for topical administration to human skin. 
     
     
         35 . The pharmaceutical composition of  claim 31 , wherein the composition is formulated for topical administration to human mucosa. 
     
     
         36 . A synthetic composition comprising human-derived  Janthinobacterium lividum  comprising a nucleic acid sequence 95% identical to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7, wherein the composition is formulated for topical application. 
     
     
         37 . The synthetic composition of  claim 36 , wherein the human-derived  Janthinobacterium lividum  comprises a nucleic acid sequence 99% identical to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7. 
     
     
         38 . The synthetic composition of  claim 36 , wherein the composition is formulated for application to a material that will be in contact with human skin, nails, hair or mucosa. 
     
     
         39 . The synthetic composition of  claim 36 , wherein the composition is formulated for application to the human skin and/or mucosa. 
     
     
         40 . The synthetic composition of  claim 36 , wherein the composition is formulated in an aqueous formulation. 
     
     
         41 . The synthetic composition of  claim 36 , wherein the composition is formulated for topical application to a surface that is contacted by a human. 
     
     
         42 . The synthetic composition of  claim 39 , wherein the composition comprises a cosmetic composition. 
     
     
         43 . The cosmetic composition of  claim 42 , wherein the cosmetic composition comprises a toothpaste, mouthwash, shampoo, soap, or dental floss. 
     
     
         44 . The cosmetic composition of  claim 42 , wherein the cosmetic composition comprises a sunscreen, moisturizer, anti-aging, probiotic or health promoting composition. 
     
     
         45 . A pharmaceutical composition comprising  Janthinobacterium lividum , wherein the  Janthinobacterium lividum  comprises a nucleic acid sequence at least 98% identical to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7 at the 16s rRNA gene sequence in an amount effective to treat, inhibit or prevent a disease, disorder, or condition associated with a pathogenic microorganism. 
     
     
         46 . A pharmaceutical composition comprising  Janthinobacterium  comprising a nucleic acid sequence comprising SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7 in an amount effective to treat, inhibit or prevent a disease, disorder, or condition associated with a pathogenic microorganism. 
     
     
         47 . A pharmaceutical composition comprising an excipient and at least one human-derived  Janthinobacterium lividum  in an amount effective to treat, inhibit or prevent a disease, disorder, or condition associated with a pathogenic microorganism. 
     
     
         48 . A method of inhibiting or preventing a pathogenic microorganism, the method comprising administering an effective amount of the human-derived  Janthinobacterium lividum  to a subject in need thereof. 
     
     
         49 . A composition, comprising a population of non-pathogenic bacteria obtained from a non-pathogenic human skin microbiome that has a 2-fold increase in at least one metabolite in the presence of a pathogenic microorganism, wherein the metabolite comprises violacein, indole-3-carboxaldehyde, prodigiosin, or a lantibiotic, wherein the composition is formulated for topical application to a subject. 
     
     
         50 . A method of treating a skin condition in a subject in need thereof, comprising administering topically to the subject a therapeutically effective amount of a pharmaceutical composition that comprises a bacterium of the genus  Janthinobacterium , wherein the bacterium comprise a nucleic acid sequence at least 95% identical to the 16s rRNA gene sequence of SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7. 
     
     
         51 . An isolated  Janthinobacterium  comprising a 16s rRNA nucleic acid sequence at least 98% identical to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7. 
     
     
         52 . A pharmaceutical composition comprising the  Janthinobacterium  of  claim 51 . 
     
     
         53 . An isolated  Janthinobacterium  comprising a 16s rRNA nucleic acid sequence at least 99% identical to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO 7. 
     
     
         54 . A pharmaceutical composition comprising the  Janthinobacterium lividum  of  claim 53   
     
     
         55 . A pharmaceutical composition, comprising at least one species of human-derived  Janthinobacterium lividum  present in an amount effective to treat, inhibit or prevent a disease, disorder, or condition associated with a pathogenic microorganism in a subject in need thereof, wherein the pharmaceutical composition is in a topical dosage form. 
     
     
         56 . A pharmaceutical composition, comprising a metabolite from at least one species of human-derived  Janthinobacterium lividum , wherein the metabolite is present in an amount sufficient for treatment, inhibition or prevention of a disease, disorder or condition associated with a pathogenic microorganism in a subject in need thereof, wherein the pharmaceutical composition is in a topical dosage form. 
     
     
         57 . A pharmaceutical composition, comprising a cell lysate of at least one species of human-derived  Janthinobacterium lividum  present in an amount effective to treat, inhibit or prevent a disease, disorder, or condition associated with a pathogenic microorganism in a subject in need thereof, wherein the pharmaceutical composition is in a topical dosage form. 
     
     
         58 . A pharmaceutical composition, comprising a Postbiotic of at least one species of human-derived  Janthinobacterium lividum  present in an amount effective to treat, inhibit or prevent a disease, disorder, or condition associated with a pathogenic microorganism in a subject in need thereof, wherein the pharmaceutical composition is in a topical dosage form. 
     
     
         59 . An isolated human-derived  Janthinobacterium lividum  that over produces violacein, indole-3-carboxaldehyde, prodigiosin, salicylate, 2,4-diamabutyrate and one or more lantibiotics in an amount effective to treat, inhibit or prevent a disease, disorder, or condition associated with a pathogenic microorganism. 
     
     
         60 . The  Janthinobacterium lividum  of  claim 59 , comprising a nucleic acid sequence at least 95% identical to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7 at the 16S rRNA sequence. 
     
     
         61 . A composition comprising the  Janthinobacterium  of  claim 59  and a physiologically acceptable carrier. 
     
     
         62 . A method for treating a skin disorder in a subject in need thereof, wherein the method comprises topically administering a formulation comprising an effective amount of probiotic bacteria, a metabolite of probiotic bacteria, postbiotic of probiotic bacteria, and/or cell lysate of probiotic bacteria; wherein the probiotic bacteria are human-derived  Janthinobacterium lividum ; and the disorder is associated with the presence of a topical pathogenic microorganism. 
     
     
         63 . The method according to  claim 62 , wherein the formulation is formulated for administration to skin or hair. 
     
     
         64 . The method according to  claim 62 , wherein the formulation is formulated for administration to mucosa. 
     
     
         65 . The method according to  claim 64 , wherein the mucosa is selected from the group consisting of mucosa of a vagina, penis, urethra, bladder, anus, mouth, nose, throat, bronchi, lungs, eye, and ear. 
     
     
         66 . A pharmaceutical composition comprising a metabolite produced from at least one human-derived  Janthinobacterium lividum  in an amount effective to treat, inhibit or prevent a disease, disorder, or condition associated with a pathogenic microorganism. 
     
     
         67 . A pharmaceutical composition comprising cell lysate from at least one human-derived  Janthinobacterium lividum  in an amount effective to treat, inhibit or prevent a disease, disorder, or condition associated with a pathogenic microorganism. 
     
     
         68 . A pharmaceutical composition comprising postbiotic from at least one human-derived  Janthinobacterium lividum  in an amount effective to treat, inhibit or prevent a disease, disorder, or condition associated with a pathogenic microorganism. 
     
     
         69 . The pharmaceutical composition of any one of  claims 66 ,  67 , and  68 , wherein the  Janthinobacterium lividum  comprises a gene sequence that is at least 95% identical to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7. 
     
     
         70 . The pharmaceutical composition of  claim 66 , wherein the composition comprises one or more compounds selected from violacein, indole-3-carboxaldehyde, prodigiosin, salicylate, 2,4-diamabutyrate and one or more lantibiotics. 
     
     
         71 . A synthetic composition comprising an effective amount of at least one human-derived  Janthinobacterium lividum  metabolite, formulated for topical application. 
     
     
         72 . The synthetic composition of  claim 71 , wherein the  Janthinobacterium lividum  comprises a 16S rRNA gene sequence that is at least 95% identical to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7. 
     
     
         73 . The synthetic composition of  claim 71 , wherein the synthetic composition is a cosmetic composition. 
     
     
         74 . The synthetic composition of  claim 71 , wherein the composition comprises one of more compounds selected from violacein, indole-3-carboxaldehyde, prodigiosin, salicylate, 2,4-diamabutyrate and one or more lantibiotics. 
     
     
         75 . A synthetic composition comprising an effective amount of human-derived  Janthinobacterium lividum  cell lysate, formulated for topical application. 
     
     
         76 . The synthetic composition of  claim 75 , wherein the  Janthinobacterium lividum  comprises a 16S rRNA gene sequence that is at least 95% identical to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7. 
     
     
         77 . The synthetic composition of  claim 75 , wherein the synthetic composition is a cosmetic composition. 
     
     
         78 . A synthetic composition comprising an effective amount of human-derived  Janthinobacterium lividum  postbiotic, formulated for topical application. 
     
     
         79 . The synthetic composition of  claim 78 , wherein the  Janthinobacterium lividum  comprises a 16S rRNA gene sequence that is at least 95% identical to SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7. 
     
     
         80 . The synthetic composition of  claim 78 , wherein the synthetic composition is a cosmetic composition. 
     
     
         81 . The cosmetic composition of  claims 73 ,  77 , and  80  wherein the cosmetic composition comprises a toothpaste, mouthwash, shampoo, soap, moisturizer, or dental floss. 
     
     
         82 . The cosmetic composition of  claims 73 ,  77 , and  80  wherein the cosmetic composition comprises a sunscreen, moisturizer, anti-aging, probiotic or health-promoting composition. 
     
     
         83 . An isolated human-derived  Janthinobacterium lividum  that over-produces 2-(alpha-D-mannosyl)-D-glyceric acid, 2-ketogluconate, 2-O-ethyl ascorbic acid, anthramycin, Aprobarbital, bendiocarb, Bis(2-ethylhexyl) phthalate, cis-5-Tetradecenoylcarnitine, Dibutyl phthalate, imidazole propionate, indole-3-carboxaldehyde, indolin-2-one, N-Acetyl-L-aspartic acid, Phosphoric acid, Phthalic acid, Pimilprost, trimethadione, or Vemolate, wherein the  Janthinobacterium lividum  is present in a composition in an amount effective to treat, inhibit or prevent a disease, disorder, or condition associated with a pathogenic microorganism.