Evidence map›Paper›PMID 31097786›Full record

ArticleScientific reports2019

Pharmaceutically modified subtilisins withstand acidic conditions and effectively degrade gluten in vivo.

Ghassan Darwish, Eva J Helmerhorst, Detlef Schuppan, Frank G Oppenheim, Guoxian Wei

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.6field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. On the Presence of Gluten-Cleaving Activity in Sodiomyces alkalinus and S. magadiensis Strains.Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections · 2023
    Article
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  6. Review
  7. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Ghassan DarwishDepartment of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine 700 Albany Street, Boston, Massachusetts, USA.
Eva J HelmerhorstDepartment of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine 700 Albany Street, Boston, Massachusetts, USA.
Detlef SchuppanDivision of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Frank G OppenheimDepartment of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine 700 Albany Street, Boston, Massachusetts, USA.
Guoxian WeiDepartment of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine 700 Albany Street, Boston, Massachusetts, USA. weigx@bu.edu.
Boston University · USJohannes Gutenberg University Mainz · DE

Funding

Gastro-intestinal microbes degrading dietary glutenR01AI087803 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI HELMERHORST, EVA JOSEPHINE · 2010 to 2014
$2.0M
Oral microbial enzymes for the treatment of celiac diseaseK02AI101067 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI HELMERHORST, EVA JOSEPHINE · 2013 to 2017
$509k
NIAID NIH HHS K02 AI101067NIAID NIH HHS R01 AI087803
6 · The paper itself

Abstract

Detoxification of gluten immunogenic epitopes is a promising strategy for the treatment of celiac disease. Our previous studies have shown that these epitopes can be degraded in vitro by subtilisin enzymes derived from Rothia mucilaginosa, a natural microbial colonizer of the oral cavity. The challenge is that the enzyme is not optimally active under acidic conditions as encountered in the stomach. We therefore aimed to protect and maintain subtilisin-A enzyme activity by exploring two pharmaceutical modification techniques: PEGylation and Polylactic glycolic acid (PLGA) microencapsulation. PEGylation of subtilisin-A (Sub-A) was performed by attaching methoxypolyethylene glycol (mPEG, 5 kDa). The PEGylation protected subtilisin-A from autolysis at neutral pH. The PEGylated Sub-A (Sub-A-mPEG) was further encapsulated by PLGA. The microencapsulated Sub-A-mPEG-PLGA showed significantly increased protection against acid exposure in vitro. In vivo, gluten immunogenic epitopes were decreased by 60% in the stomach of mice fed with chow containing Sub-A-mPEG-PLGA (0.2 mg Sub-A/g chow) (n = 9) compared to 31.9% in mice fed with chow containing unmodified Sub-A (n = 9). These results show that the developed pharmaceutical modification can protect Sub-A from auto-digestion as well as from acid inactivation, thus rendering the enzyme more effective for applications in vivo.

Indexed as

AnimalsBacillus licheniformisCapsulesDrug CarriersDrug LiberationFemaleGastric MucosaGlutensHydrogen-Ion ConcentrationMiceMice, Inbred BALB CPolyethylene GlycolsPolylactic Acid-Polyglycolic Acid CopolymerProteolysisSubtilisinCapsulesDrug CarriersGlutensPolyethylene GlycolsPolylactic Acid-Polyglycolic Acid CopolymerSubtilisin

Identifiers

PMID31097786
PMCPMC6522598
OpenAlexW2946470419

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.