Multi-omic Analysis of the Interaction between Clostridioides difficile Infection and Pediatric Inflammatory Bowel Disease.

2020

2020 Aug 11

1934-6069

<p>Children with inflammatory bowel diseases (IBD) are particularly vulnerable to infection with Clostridioides difficile (CDI). IBD and IBD&nbsp;+ CDI have overlapping symptoms but respond to distinctive treatments, highlighting the need for diagnostic biomarkers. Here, we studied pediatric patients with IBD and IBD&nbsp;+ CDI, comparing longitudinal data on the gut microbiome, metabolome, and other measures. The microbiome is dysbiotic and heterogeneous in both disease states, but the metabolome reveals disease-specific patterns. The IBD group shows increased concentrations of markers of inflammation and tissue damage compared with healthy controls, and metabolic changes associate with susceptibility to CDI. In IBD&nbsp;+ CDI, we detect both metabolites associated with inflammation/tissue damage and fermentation products produced by C.&nbsp;difficile. The most discriminating metabolite found is isocaproyltaurine, a covalent conjugate of a distinctive C.&nbsp;difficile fermentation product (isocaproate) and an amino acid associated with tissue damage (taurine), which may be useful as a joint marker of the two disease processes.</p>

10.1016/j.chom.2020.07.020

Cell Host Microbe

32822584

Risk for Chronic Kidney Disease in Patients with Inflammatory Bowel Diseases Increases with Age but is not Associated with 5-aminosalicylate Use.

2019

2019 Nov 01

1542-7714

<p><strong>BACKGROUND &amp; AIMS: </strong>It is not clear what factors affect risk of chronic kidney disease (CKD) in patients with inflammatory bowel disease (IBD); increased risk has been inconsistently associated with use of 5-aminosalicylates (5-ASAs). We aimed to calculate the relative hazard of CKD among patients with IBD, adjusted for CKD risk factors, and to determine whether IBD medications are associated with change in estimated glomerular filtration rate (eGFR).</p>

<p><strong>METHODS: </strong>We performed a retrospective cohort study of data from The Health Improvement Network. Patients with IBD (n=17,807) were matched for age, sex, and practice to individuals without IBD (n=63,466). The relative hazard of CKD, stages 3 through 5D, in patients with IBD was calculated using a Cox proportional hazards model adjusted for common CKD risk factors. We also evaluated the association of 5-ASAs, azathioprine, and methotrexate with change in eGFR using a longitudinal model.</p>

<p><strong>RESULTS: </strong>After we controlled for risk factors associated with CKD, we found IBD to be associated with development of CKD in patients 16-77 years old. As patient age increased, the adjusted hazard ratio for CKD decreased monotonically, from 7.88 (95% CI, 2.56-24.19) at age 16 to 1.13 (95% CI, 1.01-1.25) at age 77. In the longitudinal analysis, exposure to 5-ASAs or methotrexate was not associated with change in eGFR, whereas azathioprine was associated with a slightly higher eGFR (0.32 mL/min/1.73 m; 95% CI, 0.16-0.48).</p>

<p><strong>CONCLUSIONS: </strong>In a retrospective study of more than 80,000 persons, we found that IBD is associated with increased risk of CKD, and the hazard ratio is highest among younger patients. Commonly used non-biologic therapeutic agents were not associated with lower eGFR.</p>

10.1016/j.cgh.2019.10.043

Clin. Gastroenterol. Hepatol.

31683056