Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn’s Disease

Lewis, James D.; Chen, Eric Z.; Baldassano, Robert N.; Otley, Anthony; Griffiths, Anne M.; Lee, Dale; Bittinger, Kyle; Bailey, Aubrey; Friedman, Elliot S.; Hoffmann, Christian; Albenberg, Lindsey; Sinha, Rohini; Compher, Charlene; Gilroy, Erin; Nessel, Lisa; Grant, Amy; Chehoud, Christel; Li, Hongzhe; Wu, Gary D.; Bushman, Frederic D.

doi:10.1016/j.chom.2015.09.008

Cited by 666 publications

(749 citation statements)

References 52 publications

Supporting

Mentioning

696

Contrasting

Unclassified

Order By: Relevance

“…[1][2][3] IBD patients have reduced microbial diversity and alterations in the composition and function of the intestinal microbiome compare with healthy controls. [4][5][6][7] While it has been speculated that this intestinal dysbiosis could contribute to disease development, it is unclear whether IBD-associated microbes incite disease or merely respond to the mucosal changes caused by inflammation. It is also unclear whether fluctuations in the composition of the microbiome could be related to changes in disease activity in IBD, which clinically is characterized by episodic flares.…”

mentioning

confidence: 99%

Microbial, metabolomic, and immunologic dynamics in a relapsing genetic mouse model of colitis induced by T-synthase deficiency

et al. 2016

View full text Add to dashboard Cite

(2017) Microbial, metabolomic, and immunologic dynamics in a relapsing genetic mouse model of colitis induced by T-synthase deficiency, Gut Microbes, 8:1, 1-16, DOI: 10.1080/19490976.2016 To link to this article: https://doi.org/10. 1080/19490976.2016 ABSTRACTIntestinal dysbiosis is thought to confer susceptibility to inflammatory bowel disease (IBD), but it is unknown whether dynamic changes in the microbiome contribute to fluctuations in disease activity. We explored this question using mice with intestine-specific deletion of C1galt1 (also known as T-synthase) (Tsyn mice). These mice develop spontaneous microbiota-dependent colitis with a remitting/relapsing course due to loss of mucin core-1 derived O-glycans. 16S rRNA sequencing and untargeted metabolomics demonstrated age-specific perturbations in the intestinal microbiome and metabolome of Tsyn mice compare with littermate controls at weeks 3 (disease onset), 5 (during remission), and 9 (after relapse). Colitis remission corresponded to increased levels of FoxP3CRORgtCCD4C T cells in the colonic lamina propria that were positively correlated with operational taxonomic units (OTUs) in the S24-7 family and negatively correlated with OTUs in the Clostridiales order. Relapse was characterized by marked expansion of FoxP3-RORgtCCD4C T cells expressing IFNg and IL17A, which were associated with Clostridiales OTUs distinct from those negatively correlated with FoxP3CRORgtCCD4C T cells. Our findings suggest that colitis remission and relapse in the Tsyn model may reflect alterations in the microbiome due to reduced core-1 O-glycosylation that shift the balance of regulatory and pro-inflammatory T cell subsets. We investigated whether genetic variation in C1galt1 correlated with the microbiome in a cohort of 78 Crohn's disease patients and 101 healthy controls. Polymorphisms near C1galt1 (rs10486157) and its molecular chaperone, Cosmc (rs4825729), were associated with altered composition of the colonic mucosal microbiota, supporting the relevance of core-1 O-glycosylation to host regulation of the microbiome.

show abstract

mentioning

confidence: 99%

Microbial, metabolomic, and immunologic dynamics in a relapsing genetic mouse model of colitis induced by T-synthase deficiency

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Several large studies are under way in the United States and Canada to investigate the theory. In 2015, researchers at the University of Pennsylvania in Philadelphia showed that inflammation, antibiotic exposure and changes to diet independently alter the balance of gut microbes in children with Crohn's disease 7 . Treatment with a biological drug to decrease inflammation or dietary approaches seemed to normalize the composition of the microbiota.…”

Section: Risk Factorsmentioning

confidence: 99%

Epidemiology: Rising in the East

Rae¹

2016

Nature

View full text Add to dashboard Cite

INFLAMMATORY BOWEL DISEASE OUTLOOK EPIDEMIOLOGY Rising in the EastInflammatory bowel disease is a growing problem in Asia. But that increase presents a golden opportunity for research. City living and consuming convenience food are two of the factors that researchers think could be behind the increase in inflammatory bowel disease.© 2 0 1 6 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .likely to have sedentary, largely indoor lifestyles and to consume convenience diets that are high in saturated fat. Studies have linked factors such as these with IBD, but it is difficult to determine the origin in regions that have a long history of the disease. The ideal time to tease apart the complex web of environmental triggers and genetic associations, says Ng, is as urbanization is happening and before the incidence of IBD has peaked. The extent of environmental change may correlate with IBD's rise and characteristics, and could lead to new hypotheses about the causes. "The golden time for finding the cause of the disease is the next ten years, " says Ng. GENETIC CHALLENGEMore than 200 genetic variants have been associated with IBD. In the first genetic-association study of IBD to include multiple ethnic groups -Europeans, East Asians, Indians and Iranians -38 new loci (regions of the genome) with links to IBD were uncovered, 25 of which have previously been associated with other diseases or traits, such as multiple sclerosis or levels of cholesterol 2 .But the rise of IBD in Asia is not being driven by the emergence of new mutations -genetic changes occur over a much longer timescale than the global onset of IBD has taken. That does not mean, however, that genetics has nothing to offer in the quest to understand the increase of incidence in Asia. Genetic variants could provide clues to why environmental changes have greater impacts on some populations than on others, says Ananthakrishnan. Punjab state in northern India, for instance, has one of the highest incidences of ulcerative colitis in Asia -around 6 new cases in 100,000 people per year 3 . And the incidence of IBD in people of Indian descent who live in Malaysia is six times higher than that in indigenous Malaysians, and three times higher than that in those of Chinese descent 4 ; clearly, some genetic risk factor is at play. Not all the genes or variants present the same risk across the globe. For example, the ATG16L1 gene -involved in the cellular recycling process autophagy -is associated with risk of Crohn's in white populations, but is not implicated in IBD in Asian people. And NOD2, a risk gene in individuals of European ancestry that is also connected with more aggressive forms of the disease, harbours different IBD-linked variants in Asian populations. What's more, the degree to which these genes explain the disease varies between different populations. In Asia, only 3% of people with IBD have a close relative with the disease, compared with 15% of individuals in the West ...

show abstract

“…Antibiotic exposure is known to be associated with dysbiosis, and this dysbiosis has been shown to be decreased with reduced intestinal inflammation in CD [9]. There are several studies looking at the antibiotics for the treatment of luminal Crohn's disease with some evidence to support the use of ciprofloxacin and metronidazole in treating luminal disease [10].…”

Section: The Altered Microbiome In Crohn's Diseasementioning

confidence: 99%

“…Recently, a systematic review of EN to maintain remission has also shown that EN is associated with a lower risk of relapse compared to a regular diet (34% vs. 64%, p < 0.01) [8]. Dietary therapy has rapid effects on microbiota composition and reduces inflammation [9].…”

Section: The Altered Microbiome In Crohn's Diseasementioning

confidence: 99%

Probiotics and Crohn’s Disease

Kroeker¹,

Lu²

2016

New Insights Into Inflammatory Bowel Disease

View full text Add to dashboard Cite

Crohn's disease (CD) is a chronic inflammatory condition that can affect any part of the gastrointestinal tract. The human gut microbiome is altered in patients with Crohn's disease. This knowledge has led to research directed at altering the microbiome for therapeutic potential. Probiotics are an attractive therapy, both from a researcher's perspective and also from the patients' perspective. In this chapter, we will review the current clinical evidence for the use of probiotics in the treatment of Crohn's disease. These studies are divided into three categories: induction of remission, maintenance of medically induced remission, and maintenance of surgically induced remission. Unfortunately, there is insufficient evidence to support the use of probiotics in the management of Crohn's disease at this time.

show abstract

Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn’s Disease

Cited by 666 publications

References 52 publications

Microbial, metabolomic, and immunologic dynamics in a relapsing genetic mouse model of colitis induced by T-synthase deficiency

Microbial, metabolomic, and immunologic dynamics in a relapsing genetic mouse model of colitis induced by T-synthase deficiency

Epidemiology: Rising in the East

Probiotics and Crohn’s Disease

Contact Info

Product

Resources

About