Compositions and methods for modulating growth of a genetically modified gut bacterial cell

A method for modulating growth of a genetically modified bacterial cell present in a human organ, comprising:

• administering to a human a rare carbohydrate of interest that is utilized as a carbon source by the genetically modified bacterial cell, wherein less than 50% of other bacterial cells present in the human organ utilize the rare carbohydrate of interest as a carbon source.

A method for modulating growth of a genetically modified bacterial cell in an organ, comprising:

• introducing the genetically modified bacterial cell to the organ in vivo, wherein the genetically modified bacterial cell utilizes as a carbon source a rare carbohydrate of interest, wherein less than 50% of other bacterial cells present in the organ utilize the rare carbohydrate of interest as a carbon source.

A method for displacing at least a portion of a population of bacterial cells in an organ, comprising:

• introducing to the organ a genetically modified bacterial cell capable of controlled entrenchment and/or controlled colonization, and displacing at least a portion of the population of bacterial cells with the genetically modified bacterial cell.

The method of any one of the preceding claims, wherein the organ is a gut.

The method of any one of the preceding claims, wherein the genetically modified bacterial cell is a genetically modified gut resident bacterial cell.

The method of any one of the preceding claims, wherein the genetically modified bacterial cell is in the genus Bacteroides.

The method of any one of the preceding claims, wherein the genetically modified bacterial cell comprises a carbohydrate-utilization gene or gene set.

The method of any one of the preceding claims, wherein the genetically modified bacterial cell is capable of treating a metabolic disease or disorder.

The method of any one of the preceding claims, wherein the genetically modified bacterial cell comprises one or more therapeutic transgenes.

The method of any one of the preceding claims, wherein the genetically modified bacterial cell is introduced orally.

The method of any one of the preceding claims, wherein the organ comprises at least 5 other bacterial species.

The method of any one of the preceding claims, further comprising colonizing the organ with the genetically modified bacterial cell at a level of at least 1% of total bacterial cells in the organ.

A genetically modified bacterial cell that utilizes as a carbon source a rare carbohydrate of interest that is utilized as a carbon source by less than 50% of bacterial cells present in a human microbiota.

A genetically modified bacterial cell, comprising:

• a heterologous carbohydrate-utilization gene or gene set that provides the genetically modified bacterial cell with an ability to utilize as a carbon source a rare carbohydrate of interest that is utilized as a carbon source by less than 50% of bacterial cells present in a human microbiota.

A genetically modified bacterial cell, comprising:

• (i) a heterologous therapeutic transgene;
• and
• (ii) a carbohydrate-utilization gene or gene set that provides the genetically modified bacterial cell with an ability to utilize as a carbon source a rare carbohydrate of interest that is utilized as a carbon source by less than 50% of bacterial cells present in a human microbiota.

A method comprising:

• providing a bacterial cell;
• and
• genetically modifying the bacterial cell to utilize as a carbon source a rare carbohydrate of interest that is utilized as a carbon source by less than 50% of bacterial cells present in a human microbiome.

A method comprising:

• providing a bacterial cell that utilizes as a carbon source a rare carbohydrate of interest that is utilized as a carbon source by less than 50% of bacterial cells present in a human microbiome;
• and
• genetically modifying the bacterial cell to express one or more therapeutic transgenes.

A method of facilitating colonization by a genetically modified bacterial cell, the method comprising:

• (a) introducing a genetically modified bacterial cell into a gut of an individual, wherein the genetically modified bacterial cell comprises a heterologous carbohydrate-utilization gene or gene set that provides the genetically modified bacterial cell with the ability to use a carbohydrate of interest as a carbon source;
• and
• (b) administering the carbohydrate of interest to the individual, thereby providing the genetically modified bacterial cell with the carbon source.

A genetically modified bacterial cell, comprising:

• a heterologous carbohydrate-utilization gene or gene set that provides the genetically modified bacterial cell with the ability to use a rare carbohydrate of interest as a carbon source.