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. 2020 May 6;8(5):677.
doi: 10.3390/microorganisms8050677.

The Bacterial Gut Microbiota of Adult Patients Infected, Colonized or Noncolonized by Clostridioides difficile

Monique J T Crobach  1 , Quinten R Ducarmon  1   2 , Elisabeth M Terveer  1   2   3 , Celine Harmanus  1 , Ingrid M J G Sanders  1 , Kees M Verduin  4 , Ed J Kuijper  1   2   3 , Romy D Zwittink  1   2
Affiliations

The Bacterial Gut Microbiota of Adult Patients Infected, Colonized or Noncolonized by Clostridioides difficile

Monique J T Crobach et al. Microorganisms. .

Abstract

: Gut microbiota composition in patients with Clostridioides difficile colonization is not well investigated. We aimed to identify bacterial signatures associated with resistance and susceptibility to C. difficile colonization (CDC) and infection (CDI). Therefore, gut microbiota composition from patients with CDC (n = 41), with CDI (n = 41), and without CDC (controls, n = 43) was determined through 16S rRNA gene amplicon sequencing. Bacterial diversity was decreased in CDC and CDI patients (p<0.01). Overall microbiota composition was significantly different between control, CDC, and CDI patients (p = 0.001). Relative abundance of Clostridioides (most likely C. difficile) increased stepwise from controls to CDC and CDI patients. In addition, differential abundance analysis revealed that CDI patients' gut microbiota was characterized by significantly higher relative abundance of Bacteroides and Veillonella than CDC patients and controls. Control patients had significantly higher Eubacterium hallii and Fusicatenibacter abundance than colonized patients. Network analysis indicated that Fusicatenibacter was negatively associated with Clostridioides in CDI patients, while Veillonella was positively associated with Clostridioides in CDC patients. Bacterial microbiota diversity decreased in both CDC and CDI patients, but harbored a distinct microbiota. Eubacterium hallii and Fusicatenibacter may indicate resistance against C. difficile colonization and subsequent infection, while Veillonella may indicate susceptibility to colonization and infection by C. difficile.

Keywords: 16S rRNA gene amplicon sequencing; Clostridioides difficile; Clostridium difficile; colonization; gut microbiota.

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Conflict of interest statement

E.T. and E.K. are supported by an unrestricted grant from Vedanta Biosciences Inc. The sponsor had no role in the design, execution, interpretation, or writing of the study.

Figures

Figure 1
Figure 1
Violin plot of alpha diversity, as measured by the Shannon index, in control, C. difficile colonization (CDC) and C. difficile infection (CDI) patients. The box plot shows the median, 25th, and 75th percentiles, and whiskers indicate 1.5* interquartile range. * p < 0.05, ** p < 0.01, and *** p < 0.001.
Figure 2
Figure 2
Principal Coordinates Analysis (PCoA) based on unweighted (A) and weighted (B) UniFrac distances. Each sample is represented by a shape and colur according to its category. The percentage of variation explained by the two first PCoA dimensions is indicated on the respective axes.
Figure 3
Figure 3
Heatmap showing differentially abundant bacterial taxa between without previous antibiotic use (C-AB), with previous antibiotic use (C+AB), CDC and CDI patients. Bacterial taxa with a Log2 fold change of at least (-)2.25 and a Benjamini–Hochberg corrected p-value ≤ 0.05 are shown on operational taxonomic unit (OTU)-level. OTU numbers are indicated as 164858xxxxxx. A full overview can be found in Table S2A.
Figure 4
Figure 4
Association network analysis using SpiecEasi in CDI (A) and CDC (B) patients. Each node represents a single OTU and is colored according to family-level taxonomy. Green edges indicates a positive association between nodes, and red edges indicate a negative association between nodes.
See this image and copyright information in PMC

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