Compositions and methods for promoting nitric oxide production through an oral delivery system

Abstract

Probiotic compositions, particularly oral compositions, comprising one or more bacteria that are capable of producing nitrite and/or nitric oxide in a subject are provided. Some compositions further comprise nitrate/nitrate, such as a botanical source of nitrate. Some compositions further comprise botanical sources of nitrate reductase. Also, provided are methods of improving the oral and/or vascular health of a subject by orally administering a composition comprising one or more bacteria capable of producing nitric oxide. Methods of repopulating the nitric oxide producing microflora and bacterial environment in the oral cavity of a subject are also provided.

1 .- 45 . (canceled) 
     
     
         46 . A method of enhancing nitrate reduction in the oral cavity of an individual comprising
 administering to the individual a probiotic composition,   where the probiotic composition comprises a bacteria isolate or mixture that comprises one or more of  Neisseria, Veillonella, Haemophilus, Actinomyces, Granulicatella, Prevotella, Leptotrichia, Brevibacillus, Porphyromonas, Fusobacterium , and clade Gemellaceae,   wherein the composition does not contain a contaminating amount of  Lactobacillus.      
     
     
         47 . The method of  claim 46 , wherein the bacteria are selected from a group consisting essentially of  Granulicatella, Neisseria, Prevotella, Haemophilus, Fusobacterium, Brevibacillus  and clade Gemellaceae. 
     
     
         48 .- 66 . (canceled) 
     
     
         67 . The method of  claim 46 , wherein the probiotic composition comprises an effective amount of nitrate. 
     
     
         68 . The method of  claim 46 , wherein the bacteria are selected from a group consisting essentially of  Granulicatella, Neisseria, Prevotella, Haemophilus, Fusobacterium, Brevibacillus  and clade Gemellaceae. 
     
     
         69 . The method of  claim 46 , wherein the bacteria comprise one or more of the following:  Granulicatella adiacens, Haemophilus parainfluenzae, Actinomyces odontolyticus, Actinomyces viscosus, Actinomyces oris, Neisseria flavescens, Neisseria mucosa, Neisseria sicca, Neisseria subflava, Prevotella melaninogenica, Prevotella salivae, Veillonella dispar, Veillonella parvula, Veillonella atypical, Fusobacterium nucleatum , and  Brevibacillus brevis.    
     
     
         70 . The method of  claim 46 , wherein the isolated bacteria consists essentially of strains that express one or more of the following nitrate reductase genes: narG, narL, narJ, narQ, narI, napC, napB, napH, napD, napA, napG, and napF. 
     
     
         71 . The method of  claim 46 , wherein the isolated bacteria consists essentially of strains that do not express the following nitrite reductase genes: nirK, nirB, nirD, nrfF, nrfA, and nrfH. 
     
     
         72 . The method of  claim 46 , wherein the isolated bacteria consists essentially of strains that do not express nitric oxide reductase. 
     
     
         73 . The method of  claim 46 , wherein the isolated bacteria consists essentially of weak or non-acid producing bacterial strains. 
     
     
         74 . The method of  claim 46 , wherein the probiotic composition is in the form of a tablet, a capsule, a granule, powder, a gum, a biofilm, an oral liquid preparation, a food product, or a lozenge. 
     
     
         75 . The method of  claim 46 , wherein the bacteria are freeze-dried. 
     
     
         76 . The method of  claim 46 , wherein the bacteria are genetically-modified or recombinant bacteria, where a gene encoding nitric oxide reductase is suppressed. 
     
     
         77 . The method of  claim 67 , wherein the effective amount of nitrate is from a botanical source. 
     
     
         78 . The method of  claim 77 , wherein the botanical source comprises one or more of beet root, kale, artichoke, holy basil, gymnema sylvestre, ashwagandha root, salvia, St. John wort, broccoli, stevia, spinach, gingko, kelp, tribulus, eleuthero, epimedium, eucommia, hawthorn berry, rhodiola, green tea, codonopsys, panax ginseng, astragalus, pine bark, dodder seed, Schisandra, cordyceps, and mixtures thereof. 
     
     
         79 . The method of  claim 46 , wherein the probiotic composition is an oral composition. 
     
     
         80 . The method of  claim 46 , wherein the probiotic composition further comprises one or more excipients, wherein the one or more excipients comprises a substance having a pH buffering capacity. 
     
     
         81 . The method of  claim 80 , wherein the pH buffering substance is selected form the group consisting of bicarbonates, carbamides, phosphates, proteins, salts, and combinations of two or more thereof.