Bacteria engineered to treat diseases that benefit from reduced gut inflammation and/or tightened gut mucosal barrier
Genetically engineered bacteria, pharmaceutical compositions thereof, and methods of treating or preventing autoimmune disorders, inhibiting inflammatory mechanisms in the gut, and/or tightening gut mucosal barrier function are disclosed.
1. A non-pathogenic bacterium comprising: a gene cassette encoding a biosynthetic pathway for producing butyrate, wherein the gene cassette is operably linked to a fumarate and nitarate reductase regulator (FNR)-responsive promoter, wherein the bacterium is Escherichia coli strain.
2. The bacterium of claim 1 , wherein the bacterium is an auxotroph in diaminopimelic acid or an enzyme in the thymidine biosynthetic pathway.
3. A pharmaceutically acceptable composition comprising the bacterium of claim 2 ; and a pharmaceutically acceptable carrier.
4. The pharmaceutically acceptable composition of claim 3 , formulated for oral or rectal administration.
5. The bacterium of claim 1 , wherein the gene cassette is located on a chromosome in the bacterium.
6. The bacterium of claim 1 , wherein the gene cassette is located on a plasmid in the bacterium.