Inflammatory bowel disease in a Swedish twin cohort: a long-term follow-up of concordance and clinical characteristics

Halfvarson, Jonas; Bodin, Lennart; Tysk, Curt; Lindberg, Eva Hellström; Järnerot, Gunnar

doi:10.1016/s0016-5085(03)00385-8

Cited by 358 publications

(229 citation statements)

References 14 publications

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“…The primacy of environmental risk factors in the development of IBD is demonstrated in twin studies. The concordance rate for ulcerative colitis (UC) is less than 20 % and is around 50 % for Crohn's disease (CD) in monozygotic twins [2][3][4]. Of note, twin studies have not provided much support for a host genetic influence on the gut microbiota [5].…”

Section: The Gut Microbiota: the Proximate Environmental Risk Factor mentioning

confidence: 99%

The microbiota in inflammatory bowel disease

2015

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This review explores our current understanding of the complex interaction between environmental risk factors, genetic traits and the development of inflammatory bowel disease. The primacy of environmental risk factors is illustrated by the rapid increase in the incidence of the disease worldwide. We discuss how the gut microbiota is the proximate environmental risk factor for subsequent development of inflammatory bowel disease. The evolving fields of virome and mycobiome studies will further our understanding of the full potential of the gut microbiota in disease pathogenesis. Manipulating the gut microbiota is a promising therapeutic avenue.

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Section: The Gut Microbiota: the Proximate Environmental Risk Factor mentioning

confidence: 99%

The microbiota in inflammatory bowel disease

2015

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“…The twins with CD were derived from a Swedish twin population, described previously (Tysk et al, 1988;Halfvarson et al, 2003Halfvarson et al, , 2004. In short, twin pairs where at least one twin in each pair had been hospitalized for IBD, were identified by running the Swedish twin registry against the Swedish Hospital Discharge Register.…”

Section: Patient Cohortmentioning

confidence: 99%

“…For example, polymorphisms in pattern recognition receptors, such as CARD15/NOD2 that recognize microbial components, have highlighted the importance of the microbiota in pathogenesis of CD (Sartor, 2006). The genetic influence is also supported by higher concordance rates (approximately 50%) for CD occurrence in monozygotic twins (Tysk et al, 1988;Orholm et al, 2000;Halfvarson et al, 2003;Jess et al, 2005). Still, approximately 50% of identical twin pairs are discordant for CD (that is, one is diseased and one is healthy) demonstrating that environmental factors are also important for disease incidence (Loftus, 2004;Halfvarson et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Molecular analysis of the gut microbiota of identical twins with Crohn's disease

et al. 2008

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Increasing evidence suggests that a combination of host genetics and the composition of the gut microbiota are important for development of Crohn's disease (CD). Our aim was to study identical twins with CD to determine microbial factors independent of host genetics. Fecal samples were studied from 10 monozygotic twin pairs with CD (discordant n ¼ 6 and concordant n ¼ 4) and 8 healthy twin pairs. DNA was extracted, 16S rRNA genes were PCR amplified and T-RFLP fingerprints generated using general bacterial and Bacteroides group-specific primers. The microbial communities were also profiled based on their percentage G þ C contents. Bacteroides 16S rRNA genes were cloned and sequenced from a subset of the samples. The bacterial diversity in each sample and similarity indices between samples were estimated based on the T-RFLP data using a combination of statistical approaches. Healthy individuals had a significantly higher bacterial diversity compared to individuals with CD. The fecal microbial communities were more similar between healthy twins than between twins with CD, especially when these were discordant for the disease. The microbial community profiles of individuals with ileal CD were significantly different from healthy individuals and those with colonic CD. Also, CD individuals had a lower relative abundance of B. uniformis and higher relative abundances of B. ovatus and B. vulgatus. Our results suggest that genetics and/or environmental exposure during childhood, in part, determine the gut microbial composition. However, CD is associated with dramatic changes in the gut microbiota and this was particularly evident for individuals with ileal CD.

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“…Family history is a risk factor of UC, according to family and twin studies. [2][3][4] The familial risk for UC is lower than for Crohn disease and a family history for 1 is also a risk factor for the other. Accordingly, the recently described susceptibility genes for UC, i.e., IL23R and NPSR1 also predispose to Crohn disease, 5,6 whereas the TLR4 variant only predisposes to Crohn disease.…”

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confidence: 99%

Cancer risks in ulcerative colitis patients

Hemminki

Sundquist

et al. 2008

Intl Journal of Cancer

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Patients diagnosed with ulcerative colitis (UC) are known to be at an increased risk of colorectal and liver cancers and leukemia. UC is an autoimmune disease, which may present a wider spectrum of cancers. We wanted to examine the risk of cancer in a large population of UC patients in order to reach high statistical power. A UC research database was constructed by identifying UC patients from the Swedish Hospital Discharge Register and cancer patients from the Cancer Registry. Follow-up of 27,606 UC patients hospitalized for the first time during the years 1964-2004 identified 2,058 patients with cancer. Standardized incidence ratios were calculated for cancer in UC patients by comparing to subjects without hospitalization for UC. The novel tumor sites in UC patients included small intestinal (carcinoid), pancreatic, breast and prostate cancers, nonthyroid endocrine gland tumors, non-Hodgkin lymphoma and multiple myeloma. A total of 11 sites showed an increased risk, which remained at 6 sites when tumors diagnosed in the year of UC hospitalization were excluded; even chronic myeloid leukemia was in excess. Cancer risks depended on the age at first hospitalization for UC. The SIRs for colon, rectal, liver and pancreatic cancers declined by age at hospitalization for UC, while for endocrine tumors the older patients were at higher risk. Our large study identified novel subsequent cancers in UC patients. However, some of these, including small intestinal carcinoids, prostate cancers and nonthyroid endocrine tumors, may be in excess because of intensified medical surveillance of the patients.

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Inflammatory bowel disease in a Swedish twin cohort: a long-term follow-up of concordance and clinical characteristics

Cited by 358 publications

References 14 publications

The microbiota in inflammatory bowel disease

The microbiota in inflammatory bowel disease

Molecular analysis of the gut microbiota of identical twins with Crohn's disease

Cancer risks in ulcerative colitis patients

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