Enteric Infections Are Common in Patients with Flares of Inflammatory Bowel Disease

Axelrad, Jordan E.; Joelson, Andrew; Green, Peter H. R.; Lawlor, Garrett; Lichtiger, Simon; Cadwell, Ken; Lebwohl, Benjamin

doi:10.1038/s41395-018-0211-8

Cited by 74 publications

(60 citation statements)

References 38 publications

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“…This allows for the primimg of colitogenic CD8 + T cells at the gut barrier site, resulting in microbiota-dependent activation of CD8 + T cells and colitis. In line with these results, Norovirus infection has been associated with exacerbations and flares of IBD 49,50 . Our data would suggest that these flares are the result of a transient reduction in Treg cells that is compensated by the expansion and conversion of Vβ2 + T cells into Treg cells as observed in the IBD pateints with inactive disease.…”

Section: Discussionsupporting

confidence: 71%

Rapid expansion of Treg cells protects from collateral colitis following a viral trigger

et al. 2020

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Foxp3 + regulatory T (Treg) cells are essential for maintaining peripheral tolerance and preventing autoimmunity. While genetic factors may predispose for autoimmunity, additional environmental triggers, such as viral infections, are usually required to initiate the onset of disease. Here, we show that viral infection with LCMV results in type I IFN-dependent Treg cell loss that is rapidly compensated by the conversion and expansion of Vβ5 + conventional T cells into iTreg cells. Using Vβ5-deficient mice, we show that these Vβ5 + iTreg cells are dispensable for limiting anti-viral immunity. Rather, the delayed replenishment of Treg cells in Vβ5-deficient mice compromises suppression of microbiota-dependent activation of CD8 + T cells, resulting in colitis. Importantly, recovery from clinical symptoms in IBD patients is marked by expansion of the corresponding Vβ2 + Treg population in humans. Collectively, we provide a link between a viral trigger and an impaired Treg cell compartment resulting in the initiation of immune pathology.

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Section: Discussionsupporting

confidence: 71%

Rapid expansion of Treg cells protects from collateral colitis following a viral trigger

et al. 2020

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“…In contrast, in a recent study from Mayo Clinic using conventional stool testing in IBD patients presenting with flare, rate of non-CDI bacterial infections was very low (< 3%) and did not influence disease course over 1 year, as compared to IBD patients who tested negative for infection or in patients with CDI; similar to this study, conventional stool testing in our study did not identify a single non-CDI pathogen [6]. Furthermore, a recent study from Columbia University Medical Center using GPP testing in IBD patients presenting with flare showed that GPPpositive patients treated with antibiotics for non-CDI had no difference in outcomes at median follow-up of 10.5 months compared to untreated GPP-positive patients for non-CDI [11]. While further studies assessing outcomes for non-CDI in IBD patients are needed, currently a C. difficile toxin PCR only diagnostic strategy and/or increasing scrutiny prior to prescribing antibiotics for a positive GPP test is warranted.…”

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confidence: 80%

Comparison of Multiplex Gastrointestinal Pathogen Panel and Conventional Stool Testing for Evaluation of Diarrhea in Patients with Inflammatory Bowel Diseases

et al. 2018

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Background and Aims Gastrointestinal pathogen panels (GPPs) are increasingly being used for evaluation of diarrhea. The impact of these tests on patients with inflammatory bowel diseases (IBD) is unknown. We performed a time-interrupted cohort study comparing GPPs and conventional stool evaluation in patients with IBD with diarrhea. Methods We included 268 consecutive patients with IBD who underwent GPP (BioFire Diagnostics ®) (n = 134) or conventional stool culture and Clostridium difficile polymerase chain reaction testing (n = 134) during suspected IBD flare between 2012 and 2016. Primary outcome was composite of 30-day IBD-related hospitalization, surgery, or emergency department visit; secondary outcome was IBD treatment modification. Results Overall, 41/134 (30.6%) patients tested positive on GPP (18 C. difficile, 17 other bacterial infections, and 6 viral pathogens) versus 14/134 patients (10.4%, all C. difficile) testing positive on conventional testing. Rate of IBD treatment modification in response to stool testing was lower in GPP group as compared conventional stool testing group (35.1 vs. 64.2%, p < 0.01). On multivariate analysis, diagnostic evaluation with GPP was associated with three times higher odds of IBD-related hospitalization/surgery/ED visit (95% CI, 1.27-7.14), as compared to conventional stool testing. This negative impact was partly mediated by differences in ordering provider specialty, with non-gastroenterologists more likely to order GPP as compared to gastroenterologists. Conclusions In patients with suspected flare of IBD, GPPs have higher pathogen detection rate and lead to lower rate of IBD treatment modification. A diagnostic testing strategy based on GPPs is associated with higher hospital-related healthcare utilization as compared to conventional stool testing, particularly when utilized by non-gastroenterologists.

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“…Cross‐sectional studies demonstrate unique microbial signatures and T‐cell populations for IBD subtypes 6,7 . GI infection is a common cause of gut dysbiosis, and several studies have reported an association among enteric infection, functionally altered commensal bacteria, and IBD 5,8,9 . By contrast, some microbes, such as Helicobacter pylori and helminths, are inversely associated with IBD, particularly CD.…”

Section: Introductionmentioning

confidence: 99%

Systematic review: gastrointestinal infection and incident inflammatory bowel disease

Axelrad

Cadwell

Colombel

et al. 2020

Aliment Pharmacol Ther

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Background: The initiating events of chronic gastrointestinal (GI) inflammation inCrohn's disease (CD) and ulcerative colitis (UC) are not well-defined, but GI infections are implicated. Aims:To define the role of GI infections in risk of incident inflammatory bowel disease (IBD) and synthesise the current body of relevant translational data to provide biological context for associations between GI infections and IBD risk. Methods:We systematically reviewed electronic databases through February 2020.Clinical studies that provided risk estimates of the association between GI infections and incident IBD were included. Inclusion criteria were broader for translational studies aiming to define mechanisms of GI infections and predisposition to or protection from IBD. Results: Of the studies identified, 63 met full inclusion criteria. Among studies of clinical gastroenteritis, bacteria-specifically, Salmonella species, Campylobacter species and Clostridioides difficile-demonstrated consistent positive associations with risk of incident IBD. Of viruses, norovirus was associated with increased risk of incident CD. Regarding inverse associations with incident IBD, Helicobacter pylori and helminth infections were associated with a generally consistent reduced risk of IBD. Based on a qualitative analysis of the translational data, putative mechanisms involve multiple microbial and immunologic pathways. Conclusions: Based on this systematic review, certain enteric pathogens are associated with an increased risk of incident IBD, while others are potentially protective.Prospective studies are required to clarify the clinical implications of these enteric pathogens on the risk and course of IBD, and possible therapeutic or preventative benefit. | 1223 AXELRAD Et AL.

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Enteric Infections Are Common in Patients with Flares of Inflammatory Bowel Disease

Abstract: Non-Clostridium difficile enteric infections were identified in 17% of symptomatic patients with IBD. Endoscopic and histologic findings may not differentiate flare from infection. Norovirus and E.coli may play an important role in flare of IBD.

Cited by 74 publications

References 38 publications

Rapid expansion of Treg cells protects from collateral colitis following a viral trigger

Rapid expansion of Treg cells protects from collateral colitis following a viral trigger

Comparison of Multiplex Gastrointestinal Pathogen Panel and Conventional Stool Testing for Evaluation of Diarrhea in Patients with Inflammatory Bowel Diseases

Systematic review: gastrointestinal infection and incident inflammatory bowel disease

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