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Ibrahim, Ahmed
Publications (2 of 2) Show all publications
Ibrahim, A., Hugerth, L. W., Hases, L., Saxena, A., Seifert, M., Thomas, Q. A., . . . Williams, C. (2019). Colitis-induced colorectal cancer and intestinal epithelial estrogen receptor beta impact gut microbiota diversity. International Journal of Cancer, 144(12), 3086-3098
Open this publication in new window or tab >>Colitis-induced colorectal cancer and intestinal epithelial estrogen receptor beta impact gut microbiota diversity
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, no 12, p. 3086-3098Article in journal (Refereed) Published
Abstract [en]

Chronic inflammation of the colon (colitis) is a risk factor for colorectal cancer (CRC). Hormone-replacement therapy reduces CRC incidences, and the estrogen receptor beta (ERβ/ESR2) has been implicated in this protection. Gut microbiota is altered in both colitis and CRC and may influence the severity of both. Here we test the hypothesis that intestinal ERβ impacts the gut microbiota. Mice with and without intestine-specific deletion of ERβ (ERβKOVil ) were generated using the Cre-LoxP system. Colitis and CRC were induced with a single intraperitoneal injection of azoxymethane (AOM) followed by administration of three cycles of dextran sulfate sodium (DSS) in drinking water. The microbiota population were characterized by high-throughput 16S rRNA gene sequencing of DNA extracted from fecal samples (N = 39). Differences in the microbiota due to AOM/DSS and absence of ERβ were identified through bioinformatic analyses of the 16S-Seq data, and the distribution of bacterial species was corroborated using qPCR. We demonstrate that colitis-induced CRC reduced the gut microbiota diversity and that loss of ERβ enhanced this process. Further, the Bacteroidetes genus Prevotellaceae_UCG_001 was overrepresented in AOM/DSS mice compared to untreated controls (3.5-fold, p = 0.004), and this was enhanced in females and in ERβKOVil mice. Overall, AOM/DSS enriched for microbiota impacting immune system diseases and metabolic functions, and lack of ERβ in combination with AOM/DSS enriched for microbiota impacting carbohydrate metabolism and cell motility, while reducing those impacting the endocrine system. Our data support that intestinal ERβ contributes to a more favorable microbiome that could attenuate CRC development.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
AOM/DSS model, colitis-associated colon cancer, estrogen receptor beta, microbiota
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:kth:diva-244808 (URN)10.1002/ijc.32037 (DOI)000466449100019 ()30515752 (PubMedID)2-s2.0-85059884325 (Scopus ID)
Note

QC 20190304

Available from: 2019-02-27 Created: 2019-02-27 Last updated: 2019-05-20Bibliographically approved
Andersson, S., Sundberg, M., Pristovsek, N., Ibrahim, A., Jonsson, P., Katona, B., . . . Asplund, A. (2017). Insufficient antibody validation challenges oestrogen receptor beta research. Nature Communications, 8, Article ID 15840.
Open this publication in new window or tab >>Insufficient antibody validation challenges oestrogen receptor beta research
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2017 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, article id 15840Article in journal (Refereed) Published
Abstract [en]

The discovery of oestrogen receptor beta (ER beta/ESR2) was a landmark discovery. Its reported expression and homology with breast cancer pharmacological target ER alpha (ESR1) raised hopes for improved endocrine therapies. After 20 years of intense research, this has not materialized. We here perform a rigorous validation of 13 anti-ER beta antibodies, using well-characterized controls and a panel of validation methods. We conclude that only one antibody, the rarely used monoclonal PPZ0506, specifically targets ER beta in immunohistochemistry. Applying this antibody for protein expression profiling in 44 normal and 21 malignant human tissues, we detect ER beta protein in testis, ovary, lymphoid cells, granulosa cell tumours, and a subset of malignant melanoma and thyroid cancers. We do not find evidence of expression in normal or cancerous human breast. This expression pattern aligns well with RNA-seq data, but contradicts a multitude of studies. Our study highlights how inadequately validated antibodies can lead an exciting field astray.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
National Category
Nano Technology
Identifiers
urn:nbn:se:kth:diva-210349 (URN)10.1038/ncomms15840 (DOI)000403317200001 ()2-s2.0-85020892431 (Scopus ID)
Note

QC 20170704

Available from: 2017-07-04 Created: 2017-07-04 Last updated: 2019-03-11Bibliographically approved
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