Dysbiosis of Fungal Microbiota in the Intestinal Mucosa of Patients with Colorectal Adenomas

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Abstract

The fungal microbiota is an important component of the human gut microbiome and may be linked to gastrointestinal disease. In this study, the fungal microbiota of biopsy samples from adenomas and adjacent tissues was characterized by deep sequencing. Ascomycota, Glomeromycota and Basidiomycota were identified as the dominant phyla in both adenomas and adjacent tissues from all subjects. Among the 60 genera identified, the opportunist pathogens Phoma and Candida represented an average of 45% of the fungal microbiota. When analyzed at the operational taxonomic unit (OTU) level, however, a decreased diversity in adenomas was observed, and three OTUs differed significantly from the adjacent tissues. Principal Component Analysis (PCA) revealed that the core OTUs formed separate clusters for advanced and non-advanced adenomas for which the abundance of four OTUs differed significantly. Moreover, the size of adenomas and the disease stage were closely related to changes in the fungal microbiota in subjects with adenomas. This study characterized the fungal microbiota profile of subjects with adenomas and identified potential diagnostic biomarkers closely related to different stages of adenomas.

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Most cited references 26

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Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis.

Iliyan Iliev, Vincent Funari, Kent D. Taylor … (2012)

The intestinal microflora, typically equated with bacteria, influences diseases such as obesity and inflammatory bowel disease. Here, we show that the mammalian gut contains a rich fungal community that interacts with the immune system through the innate immune receptor Dectin-1. Mice lacking Dectin-1 exhibited increased susceptibility to chemically induced colitis, which was the result of altered responses to indigenous fungi. In humans, we identified a polymorphism in the gene for Dectin-1 (CLEC7A) that is strongly linked to a severe form of ulcerative colitis. Together, our findings reveal a eukaryotic fungal community in the gut (the "mycobiome") that coexists with bacteria and substantially expands the repertoire of organisms interacting with the intestinal immune system to influence health and disease.

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ITS as an environmental DNA barcode for fungi: an in silico approach reveals potential PCR biases

Eva Bellemain, Tor Carlsen, Christian Brochmann … (2010)

Background During the last 15 years the internal transcribed spacer (ITS) of nuclear DNA has been used as a target for analyzing fungal diversity in environmental samples, and has recently been selected as the standard marker for fungal DNA barcoding. In this study we explored the potential amplification biases that various commonly utilized ITS primers might introduce during amplification of different parts of the ITS region in samples containing mixed templates ('environmental barcoding'). We performed in silico PCR analyses with commonly used primer combinations using various ITS datasets obtained from public databases as templates. Results Some of the ITS primers, such as ITS1-F, were hampered with a high proportion of mismatches relative to the target sequences, and most of them appeared to introduce taxonomic biases during PCR. Some primers, e.g. ITS1-F, ITS1 and ITS5, were biased towards amplification of basidiomycetes, whereas others, e.g. ITS2, ITS3 and ITS4, were biased towards ascomycetes. The assumed basidiomycete-specific primer ITS4-B only amplified a minor proportion of basidiomycete ITS sequences, even under relaxed PCR conditions. Due to systematic length differences in the ITS2 region as well as the entire ITS, we found that ascomycetes will more easily amplify than basidiomycetes using these regions as targets. This bias can be avoided by using primers amplifying ITS1 only, but this would imply preferential amplification of 'non-dikarya' fungi. Conclusions We conclude that ITS primers have to be selected carefully, especially when used for high-throughput sequencing of environmental samples. We suggest that different primer combinations or different parts of the ITS region should be analyzed in parallel, or that alternative ITS primers should be searched for.

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High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease

Alan W. Walker, Jeremy Sanderson, Carol Churcher … (2011)

Background The gut microbiota is thought to play a key role in the development of the inflammatory bowel diseases Crohn's disease (CD) and ulcerative colitis (UC). Shifts in the composition of resident bacteria have been postulated to drive the chronic inflammation seen in both diseases (the "dysbiosis" hypothesis). We therefore specifically sought to compare the mucosa-associated microbiota from both inflamed and non-inflamed sites of the colon in CD and UC patients to that from non-IBD controls and to detect disease-specific profiles. Results Paired mucosal biopsies of inflamed and non-inflamed intestinal tissue from 6 CD (n = 12) and 6 UC (n = 12) patients were compared to biopsies from 5 healthy controls (n = 5) by in-depth sequencing of over 10,000 near full-length bacterial 16S rRNA genes. The results indicate that mucosal microbial diversity is reduced in IBD, particularly in CD, and that the species composition is disturbed. Firmicutes were reduced in IBD samples and there were concurrent increases in Bacteroidetes, and in CD only, Enterobacteriaceae. There were also significant differences in microbial community structure between inflamed and non-inflamed mucosal sites. However, these differences varied greatly between individuals, meaning there was no obvious bacterial signature that was positively associated with the inflamed gut. Conclusions These results may support the hypothesis that the overall dysbiosis observed in inflammatory bowel disease patients relative to non-IBD controls might to some extent be a result of the disturbed gut environment rather than the direct cause of disease. Nonetheless, the observed shifts in microbiota composition may be important factors in disease maintenance and severity.

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Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group

ISSN (Electronic): 2045-2322

Publication date (Electronic): 23 January 2015

Publication date Collection: 2015

Volume: 5

Electronic Location Identifier: 7980

Affiliations

[1 ]CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Key Laboratory of Microbial Drug Resistance and Resistome , Beijing 100101, China

[2 ]University of Chinese Academy of Sciences , Beijing 100049, China

[3 ]Department of Gastroenterology, Peking University People's Hospital , Beijing 100044, China

[4 ]Chinese National Human Genome Center, Beijing, 100176, China; SinoGenoMax Co. Ltd , Beijing. 100176, China

[5 ]Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou 310006, China

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[a ] zhuyuanmin@ 123456sina.com

[b ] zhubaoli@ 123456im.ac.cn

Article

Publisher Item ID: srep07980

DOI: 10.1038/srep07980

PMC ID: 4648387

PubMed ID: 25613490

SO-VID: 2403c39c-3f49-4a52-b54b-3398ace0c22a

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

Dysbiosis of Fungal Microbiota in the Intestinal Mucosa of Patients with Colorectal Adenomas

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Tick microbiome

Most cited references 26

Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis.

ITS as an environmental DNA barcode for fungi: an in silico approach reveals potential PCR biases

High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease

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