Metagenomic Analysis of Microbiome in Colon Tissue from Subjects with Inflammatory Bowel Diseases Reveals Interplay of Viruses and Bacteria

Wang, Weiwei; Jovel, Juan; Halloran, Brendan P.; Wine, Eytan; Patterson, Jordan; Ford, Glenn; OʼKeefe, Sandra; Meng, Bo; Song, Deyong; Zhang, Yong; Tian, Zhendong; Wasilenko, Shawn; Rahbari, Mandana; Reza, Salman; Mitchell, Troy; Jordan, Tracy; Carpenter, Eric J.; Madsen, Karen; Fedorak, Richard N.; Dielemann, Levinus A.; Wong, Gane Ka‐Shu; Mason, Andrew L.

doi:10.1097/mib.0000000000000344

Cited by 98 publications

(108 citation statements)

References 65 publications

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“…However, there are data in the literature, for example, derived from metagenomic analysis of the virome in colonic IBD biopsies, showing differences in the microbiome, virome and HERV expression. Most interestingly, in patients with herpesviridae in the colon, there is an increased expression of HERVs connected with differences in the diversity of the microbiome [41]. In these lines, Norman et al [42], also found disease-specific alterations in the enteric virome of IBD patients and most importantly, these changes were not secondary to changes in the microbiome, supporting the hypothesis that changes in the virome may contribute to intestinal inflammation and bacterial dysbiosis.…”

Section: Discussionsupporting

confidence: 57%

Human Endogenous Retroviruses: Residues of Ancient Times Are Differentially Expressed in Crohn’s Disease

et al. 2018

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Background: Eight percent of the human genome consists of human endogenous retroviruses (HERV). These genetic elements are remnants of ancient retroviral germ-line infections. Altered HERV expression is associated with several chronic inflammatory diseases. A physiological role of the HERV-derived proteins syncytin-1 and -2 has been described for the integrity of the human placental cell layer in terms of maintaining feto-maternal tolerance. The aim of this project was to investigate HERV expression in Crohn’s disease (CD) with a further focus on syncytins in the gut. Material and Methods: Seventy-four ileal and colonic tissue samples of CD patients and healthy controls have been investigated for mRNA expression of major HERV groups by a comprehensive microarray screening. The most prominent differences have been validated by qRT-PCR. Immunohistochemistry (IHC), Western Blot (WB) and qRT-PCR were performed for syncytin-1 and -2. Results: HERV microarray screening revealed a distinct expression profile in ileal and colonic tissue, as well as differential expression in CD compared to healthy controls. qRT-PCR validated differential expression of at least 3 HERV-groups in CD. qRT-PCR, IHC and WB showed a tissue-dependent diminished epithelial expression of syncytins in inflamed CD. Conclusion: For the first time, HERV expression has been comprehensively studied in the gut. Between CD and healthy controls we could show a tissue dependent differential HERV expression profile. Notably, we could show that syncytin-1 and -2 are expressed in the epithelial layer in ileal and colonic tissue samples, whereas their diminished tissue-dependent expression in inflamed CD might modulate inflammatory processes at the gut barrier.

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Section: Discussionsupporting

confidence: 57%

Human Endogenous Retroviruses: Residues of Ancient Times Are Differentially Expressed in Crohn’s Disease

et al. 2018

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“…Bacteriophage are viruses that infect and replicate within bacteria. They are extremely diverse and abundant, and appear to be as prevalent in the gut as bacteria(62). Temperate phages are bacteriophages which can be either lytic or lysogenic, the former representing virulent phage, whereas the latter integrate into the bacterial genome to be dormant until induction, capable of altering bacterial function and fitness.…”

Section: Intestinal Dysbiosis In Ibd Patientsmentioning

confidence: 99%

The gut microbiota and inflammatory bowel diseases

Miyoshi

Chang

2017

Translational Research

122

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Inflammatory bowel diseases (IBD) are chronic diseases of unclear etiology that affect over 1 million individuals in the United States and over 2.5 million people in Europe(1). However, they are also expanding globally, affecting populations in Asia, South America, and the Middle East as they become more industrialized. These diseases are believed to arise from the convergence of genetic, environmental, and microbial factors that trigger aberrant immune and tissue responses, resulting in intestinal inflammation. Advances in cultivation-independent investigations, experimental models, and bioinformatics approaches have improved our understanding of the role of gut microbiota in IBD. However, determining and understanding the functional consequences of gut dysbiosis and altered host-microbiota interactions in IBD remain a challenge due to the limits of current experimental models and difficulty in establishing causal links in human-based investigations. Continued development of new methodologies and improvements in clinical study design are needed to better understand the interplay of genetic, microbial, and immunological factors in IBD. This knowledge can then be applied clinically to improve therapeutic strategies and outcomes for IBD.

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“…Hypothetically, asymptomatic Norovirus infection may contribute to disruption of the stability of the GI microbiota, leading to iCD 121 . Wang et al 122 performed a metagenomic analysis of microbiome in colon tissue from patients with IBD and showed that patients with herpesviridae sequences in their colon demonstrated increased expression of human endogenous retroviral sequences and differences in the diversity of their microbiome.…”

Section: Altered Gut Microbiota: Interactions and Involvement In Ibd mentioning

confidence: 99%

Microbiota in Inflammatory Bowel Disease Pathogenesis and Therapy

Serban

2015

Nut in Clin Prac

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Inflammatory bowel disease (IBD), including ulcerative colitis, Crohn's disease, and unclassified IBD, continues to cause significant morbidity. While its incidence is increasing, no clear etiology and no cure have yet been discovered. Recent findings suggest that IBD may have a multifactorial etiology, where complex interactions between genetics, epigenetics, environmental factors (including diet but also infections, antibiotics, and sanitation), and host immune system lead to abnormal immune responses and chronic inflammation. Over the past years, the role of altered gut microbiota (in both composition and function) in IBD pathogenesis has emerged as an outstanding area of interest. According to new findings, gut dysbiosis may appear as a key element in initiation of inflammation in IBD and its complications. Moreover, complex metagenomic studies provide possibilities to distinguish between IBD types and appreciate severity and prognosis of the disease, as well as response to therapy. This review provides an updated knowledge of recent findings linking altered bacterial composition and functions, viruses, and fungi to IBD pathogenesis. It also highlights the complex genetic, epigenetic, immune, and microbial interactions in relation to environmental factors (including diet). We overview the actual options to manipulate the altered microbiota, such as modified diet, probiotics, prebiotics, synbiotics, antibiotics, and fecal transplantation. Future possible therapies are also included. Targeting altered microbiota could be the next therapeutic personalized approach, but more research and well-designed comparative prospective studies are required to formulate adequate directions for prevention and therapy.

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Metagenomic Analysis of Microbiome in Colon Tissue from Subjects with Inflammatory Bowel Diseases Reveals Interplay of Viruses and Bacteria

Abstract: Article first published online 29 April 2015.

Cited by 98 publications

References 65 publications

Human Endogenous Retroviruses: Residues of Ancient Times Are Differentially Expressed in Crohn’s Disease

Human Endogenous Retroviruses: Residues of Ancient Times Are Differentially Expressed in Crohn’s Disease

The gut microbiota and inflammatory bowel diseases

Microbiota in Inflammatory Bowel Disease Pathogenesis and Therapy

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