Metagenomic analysis reveals distinct patterns of gut microbiota features with diversified functions in C. difficile infection (CDI), asymptomatic carriage and non-CDI diarrhea
Lamei Wang,
Xinhua Chen,
Nira R. Pollock,
Javier A. Villafuerte Gálvez,
Carolyn D. Alonso,
Dangdang Wang,
Kaitlyn Daugherty,
Hua Xu,
Junhu Yao,
Yulin Chen,
Ciaran P. Kelly,
Yangchun Cao
Affiliations
Lamei Wang
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
Xinhua Chen
Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Nira R. Pollock
Division of Infectious Disease, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Javier A. Villafuerte Gálvez
Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Carolyn D. Alonso
Division of Infectious Disease, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Dangdang Wang
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
Kaitlyn Daugherty
Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Hua Xu
Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Junhu Yao
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
Yulin Chen
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
Ciaran P. Kelly
Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Yangchun Cao
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
Clostridioides difficile infection (CDI) has been recognized as a leading cause of healthcare-associated infections and a considerable threat to public health globally. Increasing evidence suggests that the gut microbiota plays a key role in the pathogenesis of CDI. The taxonomic composition and functional capacity of the gut microbiota associated with CDI have not been studied systematically. Here, we performed a comprehensive shotgun metagenomic sequencing in a well-characterized human cohort to reveal distinct patterns of gut microbiota and potential functional features associated with CDI. Fecal samples were collected from 104 inpatients, including : (1) patients with clinically significant diarrhea and positive nucleic acid amplification testing (NAAT) and received CDI treatment (CDI, n = 47); (2) patients with positive stool NAAT but without diarrhea (Carrier, n = 17); (3) patients with negative stool NAAT but with diarrhea (Diarrhea, n = 14); and (4) patients with negative stool NAAT and without diarrhea (Control, n = 26). Downstream statistical analyses (including alpha and beta diversity analysis, differential abundance analysis, correlation network analysis, and potential functional analysis) were then performed. The gut microbiota in the Control group showed higher Chao1 index (p 3.0, adjusted p 2.5, adjusted p 3.0, adjusted p < 0.05), and the contributions of phylum and species to resistance functions differed among the four groups. Our results reveal alterations of gut microbiota composition and potential functions among four groups of differential colonization/infection status of Clostridioides difficile. These findings support the potential roles of gut microbiota and their potential functions in the pathogenesis of CDI.
