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Compositions and methods for treating inflammatory bowel diseases

A composition and group technology, which can be used in drug combinations, allergic diseases, medical raw materials derived from bacteria, etc., and can solve problems such as increased incidence and prevalence.

Pending Publication Date: 2020-12-22
SERES HEALTH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Furthermore, despite available treatment options, IBD remains a major medical challenge, with both incidence and prevalence increasing worldwide

Method used

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  • Compositions and methods for treating inflammatory bowel diseases
  • Compositions and methods for treating inflammatory bowel diseases
  • Compositions and methods for treating inflammatory bowel diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0151] Example 1: Analysis of bile acid levels in patients with ulcerative colitis after administration of spore populations (HHSP) derived from feces of healthy humans

[0152] To begin to understand the role of bile acids in inflammatory bowel disease (IBD), secondary bile acids associated with the 7α-dehydroxylase pathway (i.e. DCA, LCA, 3-oxo-LCA, 3α12-oxo-deoxycholic acid and 3β12α-deoxycholic acid) levels. The treatment regimen consisted of one of the following: (A) placebo alone; (B) placebo followed by weekly dosing with spore populations ("HHSP") derived from healthy human feces; (C) vancomycin (D) vancomycin followed by daily dosing with HHSP. Bile acid concentrations were measured at four different time points: (1) baseline (i.e., before administration of vancomycin or HHSP) (“Visit 1”); (2) immediately after vancomycin treatment (when required ) (“Visit 4”); (3) 2 weeks after initiation of HHSP administration (when required) (“Visit 6”); and (4) 8 weeks after ini...

Embodiment 2

[0160] Example 2: Analysis of Bile Acid Levels in Ulcerative Colitis Patients in Remission

[0161] To assess the potential relationship between bile acid levels and disease remission, different bile acid s level. A patient with ulcerative colitis has received one of the treatment regimens described in Example 1. Bile acids were extracted from stool samples and quantified as described in Example 1 above.

[0162] Such as Figure 2A to Figure 2F as well as Figure 3A to Figure 3FAs shown in , responders expressed higher levels of the following secondary bile acids compared to non-responders: deoxycholic acid (DCA) ( Figure 2A and Figure 3A ), LCA ( Figure 2B and Figure 3B ), 3α12-oxo-deoxycholic acid ( Figure 2C and Figure 3C ), 7α3-oxo-chenodeoxycholic acid ( Figure 2D and Figure 3D ), 3-oxo-LCA ( Figure 2E and Figure 3E ), and 3β12α-oxo-deoxycholic acid (3-isodeoxycholic acid) ( Figure 2F and Figure 3F ). In contrast, levels of UDCA in non-responde...

Embodiment 3

[0164] Example 3: Evaluation of the Anti-inflammatory Effect of Secondary Bile Acids on Activated Monocytes and PBMCs

[0165] To better understand the possible relationship between increased levels of certain secondary bile acids and remission of ulcerative colitis, in the presence of different concentrations of different primary and secondary bile acids in their conjugated and unconjugated forms, Monocytes and PBMCs were activated with LPS. The amounts of TNF-[alpha] and IL-10 produced by activated cells were measured as follows.

[0166] TNF-α and IL-10 secretion assay

[0167] Human buffy coats were obtained from Bioreclamation and shipped overnight on ice. The buffy coat was diluted 1 :1 with PBS and layered over Ficoll-Paque (GE Healthcare cat# 17-1440-03) in a 50 mL falcon tube. Spin the sample non-stop at 500 x g for 20 min at room temperature. PBMCs were aspirated at the Percoll gradient layer and washed 3 times with PBS. Cells were counted with a hemocytometer t...

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Abstract

Provided herein are bacterial compositions that are useful for treating and preventing complications and side effects associated with an inflammatory bowel disease.

Description

[0001] References to Sequence Listings Submitted Electronically [0002] The contents of the electronically filed sequence listing in the ASCII text file (name: 4268.014PC01_SequenceListing_ST25.txt; size: 8,737 bytes; and creation date: March 29, 2019) filed with this application are incorporated by reference in their entirety Incorporated into this article. [0003] field of invention [0004] The present disclosure relates to bacterial compositions that modulate levels of bile acids when administered to a subject. The bacterial composition is useful for treating and / or preventing complications and side effects associated with inflammatory bowel disease. [0005] Background of the invention [0006] Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder characterized by inflammation of the bowel or colon. Symptoms of IBD can vary but typically include abdominal cramping, persistent diarrhea, and colorectal bleeding. IBD can be debilitating and, if left un...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/74A61P29/00A61P37/02A61P1/04A61P1/00
CPCA61K35/74A61P29/00A61K2300/00A61P1/00A61P37/06A61P1/04A61K35/742
Inventor M·南达库马尔E·J·奥布莱恩S·达塔
Owner SERES HEALTH