A large-sale meta-analysis of C. difficile prevalence across age, geography, health and disease.
448 gut metagenome samples from multiple countries (mainly Germany, also Luxembourg, France, and others), studied in a cross-sectional design focused on C. difficile prevalence. machine-written summary
Sequencing depth per sample · this project all projects
Sampling design and relatedness
longitudinal
44 of 143 people sampled more than once (349 samples; median 4, up to 36 per person) · follow-up median 3 mo (max 6.8 y) · median interval between samples 14 d(time from collection dates).
Each row is one person (36 shown of 44); dots are samples at days since that person's first sample.
Bacteroides 10.0%Phocaeicola 9.0%Faecalibacterium 6.2%Roseburia 5.7%Prevotella 4.9%Bifidobacterium 3.7%Lachnospira 3.1%Alistipes 3.0%Parabacteroides 2.2%Ruminococcoides 1.6%Blautia_A 1.5%Gemmiger 1.3%not assigned to a genus 6.2%other genera 41.4%
Genera, mean relative abundance over 399 profiled gut samples of this project (Sandpiper SingleM profiles, GTDB R232; low-depth and non-metagenome profiles left out).
C. difficile may be overdiagnosed in adults and is a prevalent commensal in infants 2022own_data
Details
Archive description
Clostridioides difficile is an urgent threat in hospital-acquired infections world-wide, yet the microbial composition associated with C. difficile, in particular in C. difficile infection (CDI) cases, remains poorly characterised. Here, we analysed 534 metagenomes from 10 publicly available CDI study populations. While we detected C. difficile in only 30% of CDI samples, multiple other toxigenic species capable of inducing CDI-like symptomatology were prevalent, raising concerns about CDI overdiagnosis. We further tracked C. difficile in 42,814 metagenomic samples from 253 public studies. We found that C. difficile prevalence, abundance and association with other bacterial species is age-dependent. In healthy adults, C. difficile is a rare taxon associated with an overall species richness reduction, while in healthy infants C. difficile is a common member of the gut microbiome and its presence is associated with a significant increase in species richness. More specifically, we identified a group of species co-occurring with C. difficile exclusively in healthy infants, enriched in obligate anaerobes and in species typically found in the gut microbiome of healthy adults. Overall, gut microbiome composition in presence of C. difficile in healthy infants is associated with multiple parameters linked to a healthy gut microbiome maturation towards an adult-like state. Our results suggest that C. difficile is a commensal in infants, and that its asymptomatic carriage is dependent on the surrounding microbial context.
How this project entered the registry
Classified as human gut / stool shotgun DNA metagenome of infant / toddler and adult and mixed ages by sonnet_x2 with confidence 0.65. Assay shotgun_dna.
1,048 runs over 448 samples · mean 2.60 Gbp per run (median 1.41 Gbp, total 2,729.33 Gbp; 1,048 runs with a base count) · layout PAIRED 524, SINGLE 524 · platform ILLUMINA 1,048 · models Illumina HiSeq 4000 (522), Illumina HiSeq 2500 (342), Illumina HiSeq 2000 (184) · 47% of runs with a Sandpiper profile · first public 2023-10-10