Gut Dysbiosis and Clostridioides difficile Infection in Neonates and Adults.

Iulia-Magdalena Vasilescu,Veronica Lazăr,Mariana-Carmen Chifiriuc,Gratiela Gradisteanu Pircalabioru,Coralia Bleotu,Alexandra Bolocan,Lia-Mara Diţu,Roxana Filip

doi:10.3389/fmicb.2021.651081

Abstract

In this review, we focus on gut microbiota profiles in infants and adults colonized (CDC) or infected (CDI) with Clostridioides difficile. After a short update on CDI epidemiology and pathology, we present the gut dysbiosis profiles associated with CDI in adults and infants, as well as the role of dysbiosis in C. difficile spores germination and multiplication. Both molecular and culturomic studies agree on a significant decrease of gut microbiota diversity and resilience in CDI, depletion of Firmicutes, Bacteroidetes, and Actinobacteria phyla and a high abundance of Proteobacteria, associated with low butyrogenic and high lactic acid-bacteria levels. In symptomatic cases, microbiota deviations are associated with high levels of inflammatory markers, such as calprotectin. In infants, colonization with Bifidobacteria that trigger a local anti-inflammatory response and abundance of Ruminococcus, together with lack of receptors for clostridial toxins and immunological factors (e.g., C. difficile toxins neutralizing antibodies) might explain the lack of clinical symptoms. Gut dysbiosis amelioration through administration of “biotics” or non-toxigenic C. difficile preparations and fecal microbiota transplantation proved to be very useful for the management of CDI.

Highlights

Clostridioides difficile is a Gram-positive, obligate anaerobe, spore-forming bacteria, harboring a plethora of surface and secreted proteins responsible for the colonic colonization and subsequent inflammation characteristic for C. difficile infection (CDI), among which the most important are the clostridial toxins: toxin A (TcdA) and toxin B (TcdB), and in some bacterial strains, the binary toxin CDT (Smits et al, 2016)
This review aims to present some particular aspects of gut microbiota in CDI infants and adults, taking into account that the pathophysiology of this disease suggests that the clinical manifestations occur in cases of an imbalance of the intestinal microbiota, known as dysbiosis
The available studies suggest that C. difficile colonization and infection are influenced by the presence, absence or abundance of certain bacteria in the human gut, which could generate favorable conditions for germination, proliferation and production of clostridial toxins which, on their turn, will alter the integrity of the intestinal mucosa

Summary

Introduction

Clostridioides (formerly Clostridium) difficile is a Gram-positive, obligate anaerobe, spore-forming bacteria, harboring a plethora of surface and secreted proteins responsible for the colonic colonization and subsequent inflammation characteristic for C. difficile infection (CDI), among which the most important are the clostridial toxins: toxin A (TcdA) and toxin B (TcdB), and in some bacterial strains, the binary toxin CDT (Smits et al, 2016). There is not much information available about the epidemiology of infection in infants, the carriage rate of non-toxigenic C. difficile is very high in newborns, suggesting the commensal status of this bacterium in this population segment (Sammons et al, 2013; Borali and De Giacomo, 2016). For this reason, C. difficile is not considered an enteric pathogen in infants and children affected by bloody diarrhea and younger than 12 months (Cama et al, 2019). Asymptomatic infants could be infected by toxigenic adult infectious strains both after hospitalization and even in the community, constituting a reservoir for toxigenic strains (Rousseau et al, 2011; Ferraris et al, 2020)

Objectives

Findings

Conclusion