Yangchun Cao1, Lamei Wang1, Shanlin Ke2, Javier A Villafuerte Gálvez3, Nira R Pollock4, Caitlin Barrett3, Rebecca Sprague3, Kaitlyn Daugherty3, Hua Xu3, Qianyun Lin3, Junhu Yao5, Yulin Chen5, Ciarán P Kelly3, Yang-Yu Liu6, Xinhua Chen7. 1. College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi Province, China; Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. 2. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 3. Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. 4. Division of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Department of Laboratory Medicine, Boston Children's Hospital, Boston, Massachusetts. 5. College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi Province, China. 6. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: yyl@channing.harvard.edu. 7. Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. Electronic address: xchen1@bidmc.harvard.edu.
Abstract
BACKGROUND & AIMS: Although the role of gut microbiota in Clostridioides difficile infection (CDI) has been well established, little is known about the role of mycobiota in CDI. Here, we performed mycobiome data analysis in a well-characterized human cohort to evaluate the potential of using gut mycobiota features for CDI diagnosis. METHODS: Stool samples were collected from 118 hospital patients, divided into 3 groups: CDI (n = 58), asymptomatic carriers (Carrier, n = 28), and Control (n = 32). The nuclear ribosomal DNA internal transcribed spacer 2 was sequenced using the Illumina HiSeq platform to assess the fungal composition. Downstream statistical analyses (including Alpha diversity analysis, ordination analysis, differential abundance analysis, fungal correlation network analysis, and classification analysis) were then performed. RESULTS: Significant differences were observed in alpha and beta diversity between patients with CDI and Carrier (P < .05). Differential abundance analysis identified 2 genera (Cladosporium and Aspergillus) enriched in Carrier. The ratio of Ascomycota to Basidiomycota was dramatically higher in patients with CDI than in Carrier and Control (P < .05). Correlations between host immune factors and mycobiota features were weaker in patients with CDI than in Carrier. Using 4 fungal operational taxonomic units combined with 6 host immune markers in the random forest classifier can achieve very high performance (area under the curve ∼92.38%) in distinguishing patients with CDI from Carrier. CONCLUSIONS: Our study provides specific markers of stool fungi combined with host immune factors to distinguish patients with CDI from Carrier. It highlights the importance of gut mycobiome in CDI, which may have been underestimated. Further studies on the diagnostic applications and therapeutic potentials of these findings are warranted.
BACKGROUND & AIMS: Although the role of gut microbiota in Clostridioides difficile infection (CDI) has been well established, little is known about the role of mycobiota in CDI. Here, we performed mycobiome data analysis in a well-characterized human cohort to evaluate the potential of using gut mycobiota features for CDI diagnosis. METHODS: Stool samples were collected from 118 hospital patients, divided into 3 groups: CDI (n = 58), asymptomatic carriers (Carrier, n = 28), and Control (n = 32). The nuclear ribosomal DNA internal transcribed spacer 2 was sequenced using the Illumina HiSeq platform to assess the fungal composition. Downstream statistical analyses (including Alpha diversity analysis, ordination analysis, differential abundance analysis, fungal correlation network analysis, and classification analysis) were then performed. RESULTS: Significant differences were observed in alpha and beta diversity between patients with CDI and Carrier (P < .05). Differential abundance analysis identified 2 genera (Cladosporium and Aspergillus) enriched in Carrier. The ratio of Ascomycota to Basidiomycota was dramatically higher in patients with CDI than in Carrier and Control (P < .05). Correlations between host immune factors and mycobiota features were weaker in patients with CDI than in Carrier. Using 4 fungal operational taxonomic units combined with 6 host immune markers in the random forest classifier can achieve very high performance (area under the curve ∼92.38%) in distinguishing patients with CDI from Carrier. CONCLUSIONS: Our study provides specific markers of stool fungi combined with host immune factors to distinguish patients with CDI from Carrier. It highlights the importance of gut mycobiome in CDI, which may have been underestimated. Further studies on the diagnostic applications and therapeutic potentials of these findings are warranted.
Authors: Pim T van Leeuwen; Jasper M van der Peet; Floris J Bikker; Michel A Hoogenkamp; Ana M Oliveira Paiva; Sarantos Kostidis; Oleg A Mayboroda; Wiep Klaas Smits; Bastiaan P Krom Journal: mSphere Date: 2016-11-09 Impact factor: 4.389
Authors: Bryan T Nycz; Samuel R Dominguez; Deborah Friedman; Joanne M Hilden; Diana Ir; Charles E Robertson; Daniel N Frank Journal: PLoS One Date: 2018-01-12 Impact factor: 3.240
Authors: Regina Lamendella; Justin R Wright; Jada Hackman; Christopher McLimans; David R Toole; William Bernard Rubio; Rebecca Drucker; Hoi Tong Wong; Kate Sabey; John P Hegarty; David B Stewart Journal: mSphere Date: 2018-01-10 Impact factor: 4.389
Authors: Harry Sokol; Valentin Leducq; Hugues Aschard; Hang-Phuong Pham; Sarah Jegou; Cecilia Landman; David Cohen; Giuseppina Liguori; Anne Bourrier; Isabelle Nion-Larmurier; Jacques Cosnes; Philippe Seksik; Philippe Langella; David Skurnik; Mathias L Richard; Laurent Beaugerie Journal: Gut Date: 2016-02-03 Impact factor: 23.059
Authors: Tao Zuo; Sunny H Wong; Chun Pan Cheung; Kelvin Lam; Rashid Lui; Kitty Cheung; Fen Zhang; Whitney Tang; Jessica Y L Ching; Justin C Y Wu; Paul K S Chan; Joseph J Y Sung; Jun Yu; Francis K L Chan; Siew C Ng Journal: Nat Commun Date: 2018-09-10 Impact factor: 14.919