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Bacteriophage compositions and kits and related methods

A bacteriophage and composition technology, applied in bacteriophage compositions and kits and related fields, can solve the problems of increased prevalence of microorganisms, lack of reduction or elimination, etc.

Pending Publication Date: 2021-03-09
BRIGHAM YOUNG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is a lack of compositions, methods and / or kits for reducing or eliminating obesity-associated microorganisms and / or for increasing the prevalence of "beneficial" microorganisms associated with non-obese individuals

Method used

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  • Bacteriophage compositions and kits and related methods
  • Bacteriophage compositions and kits and related methods
  • Bacteriophage compositions and kits and related methods

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0171] figure 1 is showing that mice with phage-treated gut microbiota colonized with Enterobacter cloacae strain B29 were compared with control mice colonized with Enterobacter cloacae strain B29 but not treated with phage Graphical representation of improved oral glucose tolerance. Such as figure 1 As shown, the phage cocktail inhibited B29-induced glucose intolerance. Mice were treated with oral antibiotics to deplete their native gut microbiota prior to colonization with the human pathogen Enterobacter cloacae strain B29.

[0172] At week 1, all mice received a daily dose of B29 by oral gavage and a high-fat diet (60% of total energy from fat, 20% from carbohydrates, and 20% from protein) to induce body weight gain . At week 2, the treatment group (dashed line) received 7 daily doses of phage cocktail by oral gavage. At weeks 3-8, the treatment group (black line) received phage in drinking water. The phage cocktail comprises greater than or equal to 1x10 9 Optium-12...

Embodiment 2

[0175] The test / trial was conducted over a four-week period using 17 individuals (10 males and 7 females) aged between 25 and 59 years who took a single daily dose of a phage cocktail. Said cocktail contains greater than or equal to 1x10 8 Optium-12, Optium-18, Optium-38, Optium-79, Optium-125, Optium-126, Optium-212, Optium-712, Optium-719, Optium-712 and Optium-819 of PFU, said phage has Tropism to a combination of Enterobacter cloacae, Escherichia coli and Klebsiella pneumoniae. Before being included in the composition, each phage was dosed at greater than or equal to 1.0x10 9 Titer isolation of phage.

[0176] Blood samples were collected from the participants and tested before and after a four-week period. Blood tests showed statistically significant improvements in reductions in inflammation, reductions in body weight and body mass index (BMI), and increases in high-density lipoprotein (HDL) cholesterol.

[0177] In particular, as Figure 2A As shown, seven particip...

Embodiment 3

[0181] Exemplary methods for identifying and characterizing phages for inclusion in compositions to reduce the number or concentration of bacteria associated with the gut microbiome of a mammal include at least the following methods.

[0182] Generally, the method may include: (1) collecting an environmental sample; (2) establishing an enrichment culture; (3) isolating phage from the enrichment culture; (4) purifying the phage; (5) testing the phage titer to a high concentration; (6) characterize the phage (e.g., using electron microscopy and genomic DNA isolation and sequencing); (7) perform restriction enzyme assays; (8) perform lytic activity assays; and (9) optionally prepare frozen phage stocks.

[0183] More specifically, the method may include collecting an environmental sample from soil, sewage, or other environmental sources and establishing an enrichment culture. An enrichment culture may include, for example, 25 mL of LB broth, 1 mL of target bacteria, and 1 mL of e...

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Abstract

Compositions for affecting the intestinal microbiome of a mammalian subject can include a pharmaceutically-acceptable carrier and greater than or equal to 1*104 PFU / mL or PFU / mg of bacteriophage having a tropism that includes an obesogenic and / or inflammatory bacterium associated with an intestinal microbiome of a mammal. Processes for preparing the disclosed compositions can include isolating thebacteriophage from an environmental source, characterizing the bacteriophage, and combining the bacteriophage with the pharmaceutically acceptable carrier at greater than or equal to1*104 PFU / mL or PFU / mg. Methods can include administering the disclosed compositions to a mammalian subject with or without co-administration of the disclosed probiotics. Administering the disclosed compositions can reduce a concentration of obesogenic and / or inflammatory bacteria in the intestinal microbiome of the mammalian subject, promote or induce weight loss, reduce inflammation, support metabolic health, and / or support a healthy balance / diversity within the intestinal microbiome of the mammalian subject.

Description

[0001] Cross References to Related Applications [0002] This application claims priority and benefit to U.S. Provisional Patent Application Serial No. 62 / 675,652, entitled "Methods and Compositions for Treating Chronic Diseases with Phages," filed May 23, 2018, and filed on March 2019. Priority to U.S. Provisional Patent Application Serial No. 62 / 815,844, entitled "Bacteriophage Compositions and Methods of Use," filed on March 8. Each of the foregoing is incorporated herein by reference in its entirety. technical field [0003] The present invention generally relates to compositions comprising one or more bacteriophages, kits comprising said compositions, and methods of making and using or administering said compositions to affect the intestinal tract of a mammalian subject The method of bacterial number or concentration within the microbiome is preferably used to promote or induce weight loss, reduce inflammation, support metabolic health and / or support healthy balance / dive...

Claims

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Application Information

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IPC IPC(8): A61K35/741A61K9/00A61P3/04A61K35/76A01N63/50
CPCA61K9/0053A61K9/0048A61K35/76A61P3/04A61K35/741Y02A50/30A01N63/50A01N63/20
Inventor 劳拉·桥水赵公泽
Owner BRIGHAM YOUNG UNIV
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