Compositions and uses thereof for treating inflammatory diseases and probiotic compositions
The invention relates to compositions and uses thereof in methods for treating an inflammatory disease, disorder or condition in a subject, in particular an inflammatory disease, disorder or condition of the digestive tract such as inflammatory bowel disease (IBD) and/or colorectal cancer. The invention also relates to probiotic compositions and the use of the compositions for treating gastrointestinal disorders.
1. A composition comprising genetically engineered anaerobic bacteria that produce 3-hydroxybutyrate (3-HB), and an orally ingestible solid carrier, for delivering 3-HB to the lumen of the GI tract.
2. A composition according to claim 1 , wherein the bacteria comprise a non-native gene capable of expressing (R)-3-hydroxybutyryl-CoA dehydrogenase.
3. A composition according to claim 1 , wherein the bacteria are Clostridia bacteria, bacteria from cluster I, IV and/or XIVa of Clostridia, bacteria from the Clostridium genus or Clostridium butyricum.
4. A composition according to claim 1 , wherein the bacteria have native genes encoding phosphotransbutyrylase and/or butyrate kinase.
5. A composition according to claim 1 , wherein the bacteria produce (R)-3-hydroxybutyrate as the sole fermentation product or produce (R)-3-hydroxybutyrate in combination with acetate and/or butyrate as fermentation products.
6. A composition according to claim 1 further comprising a pharmaceutically acceptable carrier for use as a medicament.
7. A composition according to claim 1 for use in treating an inflammatory disease; for use in treating a gastrointestinal disorder; for use in treating gastrointestinal dysbiosis; for use in treating C. difficile infection; for use in modulating gut flora; or for use in animal feed.
8. A composition according to claim 7 , wherein the inflammatory disease or gastrointestinal disorder is inflammatory bowel disease, irritable bowel syndrome, Crohn's disease, Pouchitis, Diverticulitis, ulcerative colitis, or colon cancer.
9. A composition according to claim 1 for use in food products.
10. A composition according to claim 9 , wherein the food product is a beverage, a drink a food supplement, or a nutraceutical.
11. A composition according to claim 1 , wherein the genetically engineered anaerobic bacteria produce (R)-3-hyroxybutyrate ((R)-3-HB).
12. A composition according to claim 1 , wherein the bacteria naturally produce butyrate.
13. A composition according to claim 6 , wherein the composition delivers the 3-HB to the large intestine, an anaerobic section of the large intestine, the colon, the terminal ileum, or a combination thereof.