COMPOSITIONS AND METHODS FOR TREATING INFLAMMATORY BOWEL DISEASES
Provided herein are bacterial compositions that are useful for treating and preventing complications and side effects associated with an inflammatory bowel disease.
1 . A composition comprising a purified population of bacteria, wherein the purified population of bacteria comprises Flavonifractor_SC49, Clostridium leptum , or a combination thereof, and wherein the composition can modulate the level of a secondary bile acid when administered to a subject.
2 . The composition of claim 1 , wherein the purified population of bacteria comprises Flavonifractor_SC49.
3 . The composition of claim 1 , wherein the purified population of bacteria comprises Clostridium leptum.
4 . The composition of claim 1 , wherein the purified population of bacteria comprises both Flavonifractor_SC49 and Clostridium leptum.
5 . The composition of any one of claims 1 , 2 , and 4 , wherein the Flavonifractor_SC49 comprises a 16S rDNA sequence that is at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to a 16S rDNA sequence of a reference Flavonifractor_SC49 OTU (SEQ ID NOs: 1, 3, or 4).
6 . The composition of any one of claims 1 and 3 to 5 , wherein the Clostridium leptum comprises a 16S rDNA sequence that is at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to a 16S rDNA sequence of a reference Clostridium leptum OTU (SEQ ID NO: 2).
7 . The composition of any one of claims 1 to 6 , wherein the secondary bile acid comprises deoxycholic acid (DCA), 3α 12-oxo-deoxycholic acid, 3β 12α-deoxycholic acid (3-isodeoxycholic acid), 7α 3-oxo-chenodeoxycholic acid, lithocholic acid (LCA), 3-oxo LCA, or combinations thereof.
8 . The composition of any one of claims 1 to 6 , wherein the secondary bile acid comprises ursodeoxycholic acid (UDCA).
9 . A method of modulating the level of a secondary bile acid in a subject in need thereof, comprising administering to the subject an effective amount of a composition of any one of claims 1 to 8 .
10 . A method of ameliorating one or more signs or symptoms of an inflammatory bowel disease (IBD) or maintaining a remission of an IBD in a subject in need thereof, comprising administering to the subject an effective amount of a composition of any one of claims 1 to 8 .
11 . The method of claim 9 or 10 , wherein the secondary bile acid comprises deoxycholic acid (DCA), 3α 12-oxo-deoxycholic acid, 3β 12α-deoxycholic acid (3-isodeoxycholic acid), 7α 3-oxo-chenodeoxycholic acid, lithocholic acid (LCA), 3-oxo LCA, or combinations thereof.
12 . The method of claim 11 , wherein the administration increases the level of the secondary bile acid in the subject.
13 . The method of claim 12 , wherein the level of the secondary bile acid is increased by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% in the subject compared to a reference (e.g., corresponding level in a subject that did not receive the composition).
14 . The method of claim 12 or 13 , wherein the increase in the level of the secondary bile acid is associated with a remission of the IBD.
15 . The method of any one of claims 11 to 14 , wherein the secondary bile acid can decrease production of TNF-α and/or increase production of IL-10 in a lipopolysaccharide (LPS)-stimulated monocyte in vitro.
16 . The method of any one of claims 11 to 15 , wherein the secondary bile acid can decrease production of TNF-α and/or increase production of IL-10 in LPS-stimulated peripheral blood mononuclear cells (PBMCs) in vitro.
17 . The method of any one of claims 11 to 16 , wherein the secondary bile acid can decrease production of IL-8 in TNFα-stimulated intestinal epithelial cells in vitro.
18 . The method of claim 9 or 10 , wherein the secondary bile acid comprises ursodeoxycholic acid (UDCA).
19 . The method of claim 18 , wherein the administration decreases the level of UDCA in the subject.
20 . The method of claim 19 , wherein the level of UDCA is decreased by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% in the subject compared to a reference (e.g., corresponding level in a subject that did not receive the composition).
21 . The method of claim 19 or 20 , wherein the decrease in the level of UDCA is associated with a remission of the IBD.
22 . The method of any one of claims 10 to 21 , wherein the IBD is ulcerative colitis or Crohn's disease.