Descriptive Study of Gut Microbiota in Infected and Colonized Subjects by Clostridiodes difficile

Abstract

Clostridiodes difficile can lead to a range of situations from the absence of symptoms (colonization) to severe diarrhea (infection). Disruption of gut microbiota provides an ideal environment for infection to occur. Comparison of gut microbiota of infected and colonized subjects could provide relevant information on susceptible groups or protectors to the development of infection, since the presence of certain genera could be related to the inhibition of transition from a state of colonization to infection. Through high-throughput sequencing of 16S rDNA gene, we performed alpha and beta diversity and composition studies on 15 infected patients (Group CDI), 15 colonized subjects (Group P), and 15 healthy controls (Group CTLR). A loss of alpha diversity and richness and a different structure have been evidenced in the CDI and P groups with respect to the CTRL group, but without significant differences between the first two. In CDI and P groups, there was a strong decrease in phylum Firmicutes and an expansion of potential pathogens. Likewise, there was a loss of inhibitory genus of C. difficile germination in infected patients that were partially conserved in colonized subjects. Therefore, infected and colonized subjects presented a gut microbiota that was completely different from that of healthy controls, although similar to each other. It is in composition where we found that colonized subjects, especially in minority genera, presented differences with respect to those infected.

Characterization of the gut microbiome of patients with Clostridioides difficile infection, patients with non–C. difficile diarrhea, and C. difficile–colonized patients

“…These contradictions in the literature may be due to the different methodologies used for sample extraction, amplification, and analysis, together with the limited number of samples processed. Consistent with other observations in the literature, we also found a decrease in Actinobacteria and an increase in Proteobacteria in patients with CDI compared to healthy individuals ( Amrane et al., 2019 ; Han et al., 2019 ; Han et al., 2020 ; Sánchez-Pellicer et al., 2021 ). When we assessed the genera by groups, we found that Ruminococcus , Clostridium _IV, Streptococcus , Acinetobacter , and Megamonas decreased in the CDI group compared to CDI.…”

“…Consistent with the literature, the lowest diversity and richness values were recorded for patients with R-CDI (Chang et al, 2008;Allegretti et al, 2016;Gazzola et al, 2020). Both our data and that of other authors show the existing damage to the microbiota or dysbiosis in patients with diarrhea due to C. difficile or other causes and that of patients colonized by C. difficile (Sangster et al, Sokol et al, 2018;Crobach et al, 2020;Sańchez-Pellicer et al, 2021;Wan et al, 2022). In addition, the greater damage to the microbiota in patients with repeated episodes of CDI is highlighted.…”

“…As for differences in abundance, we found that, except in patients with CDI, the most abundant phylum in all five groups was Firmicutes followed by Bacteroidetes. In the CDI group, this order was inverted, with Bacteroidetes being the most abundant phylum, as reported elsewhere ( Antharam et al., 2013 ; Sánchez-Pellicer et al., 2021 ), although the opposite has also been observed ( Zhang et al., 2015 ; Han et al., 2019 ; Han et al., 2020 ). These contradictions in the literature may be due to the different methodologies used for sample extraction, amplification, and analysis, together with the limited number of samples processed.…”

“…Among the few studies comparing the intestinal microbiota of patients with CDI and C. difficile colonization, the number of patients included is lower than in ours, with very few significant differences between the two groups ( Zhang et al., 2015 ; Han et al., 2019 ; Crobach et al., 2020 ; Sánchez-Pellicer et al., 2021 ). Furthermore, the study conducted by Han et al.…”

“…Several studies have characterized microbiota in patients with CDI, although the groups compared were very heterogeneous. Some studies based their control group on “healthy” individuals, which is a confusing term, since “healthy” can include patients with other diseases but not CDI or diarrhea, patients receiving different treatments for their underlying disease, persons without diarrhea who have not taken antibiotics, and even stool donors for fecal transplantation ( Schubert et al., 2014 ; Milani et al., 2016 ; Amrane et al., 2019 ; Sánchez-Pellicer et al., 2021 ). We compared various groups, including both healthy individuals and patients with diarrhea in whom C. difficile has been ruled out but who share diseases, treatments, and other characteristics that may more closely resemble those of CDI patients.…”