Dataset Information

Phospholipase A₂ of Microbiota as Pathogenetic Determinant to Induce Inflammatory States in Ulcerative Colitis: Therapeutic Implications of Phospholipase A₂ Inhibitors.

ABSTRACT:

Background

Attack by commensal microbiota is one component of induction of inflammatory episodes in ulcerative colitis (UC). In UC, the mucus layer is intrinsically devoid of phosphatidylcholine (PC) resulting in low hydrophobicity which facilitates bacterial invasion. Colonic ectophospholipase-carrying bacterial strains are likely candidates to further thinning the PC mucus barrier and to precipitate inflammatory episodes.

Objective

To evaluate the effect of phospholipase A₂ (PLA₂) inhibitors on inflammation in a genetic UC mouse model.

Methods

As PLA₂ inhibitor, we applied the bile acid-phospholipid conjugate ursodeoxycholate-lysophosphatidylethanolamide (UDCA-LPE) or as control 5% Tween 80 by oral gavage to intestine-specific kindlin 2 knockout mice.

Results

Luminal UDCA-LPE reduced the PLA₂ activity in stool by 36 ± 8%. Concomitantly no inflammatory phenotype was observed when compared to kindlin 2^(-/-) mice not treated with UDCA-LPE. The improvement was documented in regard to stool consistency, calprotectin levels in stool, and macroscopic/endoscopic as well as histologic features of the mucosa. The pattern of colonic microbiota distribution obtained in the UC phenotype mice was reversed by UDCA-LPE to the control mice pattern.

Conclusion

The inhibition of the bacterial ectophospholipase A₂ activity improves mucosal inflammation in a genetic mouse model of UC. It is assumed that the remaining mucus PC shield is better preserved when luminal PLA₂ is suppressed.

SUBMITTER: Stremmel W

PROVIDER: S-EPMC5988128 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Publications

Phospholipase A<sub>2</sub> of Microbiota as Pathogenetic Determinant to Induce Inflammatory States in Ulcerative Colitis: Therapeutic Implications of Phospholipase A<sub>2</sub> Inhibitors.

Stremmel Wolfgang W Staffer Simone S Stuhrmann Nicole N Gan-Schreier Hongying H Gauss Annika A Burger Nina N Hornuss Daniel D

Inflammatory intestinal diseases 20180306 3

<h4>Background</h4>Attack by commensal microbiota is one component of induction of inflammatory episodes in ulcerative colitis (UC). In UC, the mucus layer is intrinsically devoid of phosphatidylcholine (PC) resulting in low hydrophobicity which facilitates bacterial invasion. Colonic ectophospholipase-carrying bacterial strains are likely candidates to further thinning the PC mucus barrier and to precipitate inflammatory episodes.<h4>Objective</h4>To evaluate the effect of phospholipase A<sub>2 ...[more]

PMID: 29922677

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Project description:Ulcerative colitis (UC) is a complex chronic pathological condition of the gut in which microbiota targeted treatment, such as fecal microbiota transplantation (FMT), has shown an encouraging effect. The aim of the present study was to investigate the efficacy and safety of FMT in patients with mild or moderate UC. A single-center, open-label study was designed, including 47 patients with mild or moderate active UC who received three treatments of fresh FMT via colonic transendoscopic enteral tubing within 1 week. The inflammatory bowel disease questionnaire, partial Mayo scores, colonoscopy, erythrocyte sedimentation rate, C-reactive protein level and procalcitoin values were used to assess the efficacy of FMT and alteration in gut microbiota was detected by 16S ribosomal RNA-sequencing. Before FMT, microbiota Faecalibacterium prausnitzii (F. prausnitzii) levels were significantly decreased in patients with UC compared with healthy donors (P<0.01). At 4 weeks post-FMT, F. prausnitzii levels were significantly increased (P<0.05), and the Mayo score was significantly decreased (1.91±1.07 at baseline vs. 4.02±1.47 at week 4; P<0.001) in patients with UC compared with healthy donors. Steroid-free clinical responses were reported in 37 patients (84.1%), and steroid-free clinical remission was achieved in 31 patients (70.5%) at week 4 post-FMT, however, steroid-free remission was not achieved in any patient. No adverse events were reported in 41 (93.2%) patients after FMT or during the 12-week follow-up. Shannon's diversity index and Chao1 estimator were also improved in patients with UC receiving FMT. In conclusion, the results of the present study suggested that FMT resulted in clinical remission in patients with mild to moderate UC, and that the remission may be associated with significant alterations to the intestinal microbiota of patients with UC. Furthermore, F. prausnitzii may serve as a diagnostic and therapeutic biomarker for the use of FMT in UC.

Dataset Information

Phospholipase A₂ of Microbiota as Pathogenetic Determinant to Induce Inflammatory States in Ulcerative Colitis: Therapeutic Implications of Phospholipase A₂ Inhibitors.

Background

Objective

Methods

Results

Conclusion

Publications

Phospholipase A<sub>2</sub> of Microbiota as Pathogenetic Determinant to Induce Inflammatory States in Ulcerative Colitis: Therapeutic Implications of Phospholipase A<sub>2</sub> Inhibitors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Phospholipase A2 of Microbiota as Pathogenetic Determinant to Induce Inflammatory States in Ulcerative Colitis: Therapeutic Implications of Phospholipase A2 Inhibitors.

Background

Objective

Methods

Results

Conclusion

Publications

Phospholipase A<sub>2</sub> of Microbiota as Pathogenetic Determinant to Induce Inflammatory States in Ulcerative Colitis: Therapeutic Implications of Phospholipase A<sub>2</sub> Inhibitors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Phospholipase A₂ of Microbiota as Pathogenetic Determinant to Induce Inflammatory States in Ulcerative Colitis: Therapeutic Implications of Phospholipase A₂ Inhibitors.