BACKGROUND: Clostridioides difficile infection and colonization are common in pediatric Crohn's disease (CD). Our aims were to test the relationship between C. difficile positivity and bowel resection surgery and to characterize microbial shifts associated with C. difficile carriage and surgery. METHODS: A retrospective single-center study of 75 pediatric CD patients tested for association between C. difficile carriage and bowel resection surgery. A prospective single-center study of 70 CD patients utilized C. difficile testing and shotgun metagenomic sequencing of fecal samples to define microbiota variation stratified by C. difficile carriage or history of surgery. RESULTS: The rate of bowel resection surgery increased from 21% in those without C. difficile to 67% in those with (P = 0.003). From a Kaplan-Meier survival model, the hazard ratio for time to first surgery was 4.4 (95% CI, 1.2-16.2; P = 0.00) in patients with positive C. difficile testing in the first year after diagnosis. Multivariable logistic regression analysis confirmed this association (odds ratio 16.2; 95% CI, 2.2-120; P = 0.006). Larger differences in microbial abundance and metabolic pathways were observed in patients with prior surgery than in those with C. difficile carriage. Depletion of Alistipes and Ruminococcus species and reduction in methionine biosynthesis were noted in patients with both C. difficile carriage and past surgery. CONCLUSIONS: A positive C. difficile test during the first year after diagnosis is associated with decreased time to first bowel resection surgery in pediatric Crohn's disease. Depletion of beneficial commensals and methionine biosynthesis in patients with C. difficile carriage may contribute to increased risk for surgery.
BACKGROUND: Clostridioides difficile infection and colonization are common in pediatric Crohn's disease (CD). Our aims were to test the relationship between C. difficile positivity and bowel resection surgery and to characterize microbial shifts associated with C. difficile carriage and surgery. METHODS: A retrospective single-center study of 75 pediatric CD patients tested for association between C. difficile carriage and bowel resection surgery. A prospective single-center study of 70 CD patients utilized C. difficile testing and shotgun metagenomic sequencing of fecal samples to define microbiota variation stratified by C. difficile carriage or history of surgery. RESULTS: The rate of bowel resection surgery increased from 21% in those without C. difficile to 67% in those with (P = 0.003). From a Kaplan-Meier survival model, the hazard ratio for time to first surgery was 4.4 (95% CI, 1.2-16.2; P = 0.00) in patients with positive C. difficile testing in the first year after diagnosis. Multivariable logistic regression analysis confirmed this association (odds ratio 16.2; 95% CI, 2.2-120; P = 0.006). Larger differences in microbial abundance and metabolic pathways were observed in patients with prior surgery than in those with C. difficile carriage. Depletion of Alistipes and Ruminococcus species and reduction in methionine biosynthesis were noted in patients with both C. difficile carriage and past surgery. CONCLUSIONS: A positive C. difficile test during the first year after diagnosis is associated with decreased time to first bowel resection surgery in pediatric Crohn's disease. Depletion of beneficial commensals and methionine biosynthesis in patients with C. difficile carriage may contribute to increased risk for surgery.
Authors: James D Lewis; Eric Z Chen; Robert N Baldassano; Anthony R Otley; Anne M Griffiths; Dale Lee; Kyle Bittinger; Aubrey Bailey; Elliot S Friedman; Christian Hoffmann; Lindsey Albenberg; Rohini Sinha; Charlene Compher; Erin Gilroy; Lisa Nessel; Amy Grant; Christel Chehoud; Hongzhe Li; Gary D Wu; Frederic D Bushman Journal: Cell Host Microbe Date: 2017-08-09 Impact factor: 21.023
Authors: Subra Kugathasan; Lee A Denson; Thomas D Walters; Mi-Ok Kim; Urko M Marigorta; Melanie Schirmer; Kajari Mondal; Chunyan Liu; Anne Griffiths; Joshua D Noe; Wallace V Crandall; Scott Snapper; Shervin Rabizadeh; Joel R Rosh; Jason M Shapiro; Stephen Guthery; David R Mack; Richard Kellermayer; Michael D Kappelman; Steven Steiner; Dedrick E Moulton; David Keljo; Stanley Cohen; Maria Oliva-Hemker; Melvin B Heyman; Anthony R Otley; Susan S Baker; Jonathan S Evans; Barbara S Kirschner; Ashish S Patel; David Ziring; Bruce C Trapnell; Francisco A Sylvester; Michael C Stephens; Robert N Baldassano; James F Markowitz; Judy Cho; Ramnik J Xavier; Curtis Huttenhower; Bruce J Aronow; Greg Gibson; Jeffrey S Hyams; Marla C Dubinsky Journal: Lancet Date: 2017-03-02 Impact factor: 79.321
Authors: Grant E Barber; Steven Hendler; Philip Okafor; David Limsui; Berkeley N Limketkai Journal: Inflamm Bowel Dis Date: 2018-07-12 Impact factor: 5.325
Authors: Jonas Halfvarson; Colin J Brislawn; Regina Lamendella; Yoshiki Vázquez-Baeza; William A Walters; Lisa M Bramer; Mauro D'Amato; Ferdinando Bonfiglio; Daniel McDonald; Antonio Gonzalez; Erin E McClure; Mitchell F Dunklebarger; Rob Knight; Janet K Jansson Journal: Nat Microbiol Date: 2017-02-13 Impact factor: 17.745
Authors: Melanie Schirmer; Eric A Franzosa; Jason Lloyd-Price; Lauren J McIver; Randall Schwager; Tiffany W Poon; Ashwin N Ananthakrishnan; Elizabeth Andrews; Gildardo Barron; Kathleen Lake; Mahadev Prasad; Jenny Sauk; Betsy Stevens; Robin G Wilson; Jonathan Braun; Lee A Denson; Subra Kugathasan; Dermot P B McGovern; Hera Vlamakis; Ramnik J Xavier; Curtis Huttenhower Journal: Nat Microbiol Date: 2018-01-08 Impact factor: 17.745
Authors: Ramnik J Xavier; Curtis Huttenhower; Jason Lloyd-Price; Cesar Arze; Ashwin N Ananthakrishnan; Melanie Schirmer; Julian Avila-Pacheco; Tiffany W Poon; Elizabeth Andrews; Nadim J Ajami; Kevin S Bonham; Colin J Brislawn; David Casero; Holly Courtney; Antonio Gonzalez; Thomas G Graeber; A Brantley Hall; Kathleen Lake; Carol J Landers; Himel Mallick; Damian R Plichta; Mahadev Prasad; Gholamali Rahnavard; Jenny Sauk; Dmitry Shungin; Yoshiki Vázquez-Baeza; Richard A White; Jonathan Braun; Lee A Denson; Janet K Jansson; Rob Knight; Subra Kugathasan; Dermot P B McGovern; Joseph F Petrosino; Thaddeus S Stappenbeck; Harland S Winter; Clary B Clish; Eric A Franzosa; Hera Vlamakis Journal: Nature Date: 2019-05-29 Impact factor: 49.962
Authors: M Ellen Kuenzig; Eric I Benchimol; Charles N Bernstein; Alain Bitton; Matthew W Carroll; Anne M Griffiths; Gilaad G Kaplan; Geoffrey C Nguyen; Anthony R Otley; Therese A Stukel; Trevor J B Dummer; Wael El-Matary; Kevan Jacobson; Jennifer L Jones; Lisa M Lix; David R Mack; Sanjay K Murthy; Juan-Nicolás Peña-Sánchez; Laura E Targownik; Stephen G Fung; Sarah Spruin; Stephanie Coward; Yunsong Cui; Christopher Filliter; Zoann Nugent; Shabnaz Siddiq; Harminder Singh Journal: J Pediatr Gastroenterol Nutr Date: 2022-06-07 Impact factor: 3.288
Authors: Allison D Ta; Nicholas J Ollberding; Rebekah Karns; Yael Haberman; Adina L Alazraki; David Hercules; Robert Baldassano; James Markowitz; Melvin B Heyman; Sandra Kim; Barbara Kirschner; Jason M Shapiro; Joshua Noe; Maria Oliva-Hemker; Anthony Otley; Marian Pfefferkorn; Richard Kellermayer; Scott Snapper; Shervin Rabizadeh; Ramnik Xavier; Marla Dubinsky; Jeffrey Hyams; Subra Kugathasan; Anil G Jegga; Jonathan R Dillman; Lee A Denson Journal: Inflamm Bowel Dis Date: 2021-10-20 Impact factor: 5.325
Authors: C Rodríguez; E Romero; L Garrido-Sanchez; G Alcaín-Martínez; R J Andrade; B Taminiau; G Daube; E García-Fuentes Journal: Gut Microbes Date: 2020-03-04