Persistent Systemic Microbial Translocation, Inflammation, and Intestinal Damage During Clostridioides difficile Infection

Alessandra Oliva; Lucia Aversano; Massimiliano De Angelis; Maria Teresa Mascellino; Maria Claudia Miele; Sergio Morelli; Riccardo Battaglia; Jessica Iera; Giovanni Bruno; Enrico Stefano Corazziari; Maria Rosa Ciardi; Mario Venditti; Claudio Maria Mastroianni; Vincenzo Vullo

doi:10.1093/ofid/ofz507

Persistent Systemic Microbial Translocation, Inflammation, and Intestinal Damage During Clostridioides difficile Infection

Open Forum Infect Dis. 2019 Dec 3;7(1):ofz507. doi: 10.1093/ofid/ofz507. eCollection 2020 Jan.

Authors

Affiliations

¹ Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
² IRCCS INM Neuromed, Pozzilli, Italy.
³ Department of Internal Medicine and Medical Specialties, Gastroenterology Unit, Sapienza University of Rome, Rome, Italy.
⁴ Humanitas Clinical and Research Hospital, Rozzano, Italy.

Abstract

Background: Clostridioides difficile infection (CDI) might be complicated by the development of nosocomial bloodstream infection (n-BSI). Based on the hypothesis that alteration of the normal gut integrity is present during CDI, we evaluated markers of microbial translocation, inflammation, and intestinal damage in patients with CDI.

Methods: Patients with documented CDI were enrolled in the study. For each subject, plasma samples were collected at T0 and T1 (before and after CDI therapy, respectively), and the following markers were evaluated: lipopolysaccharide-binding protein (LPB), EndoCab IgM, interleukin-6, intestinal fatty acid binding protein (I-FABP). Samples from nonhospitalized healthy controls were also included. The study population was divided into BSI+/BSI- and fecal microbiota transplantation (FMT) +/FMT- groups, according to the development of n-BSI and the receipt of FMT, respectively.

Results: Overall, 45 subjects were included; 8 (17.7%) developed primary n-BSI. Markers of microbial translocation and intestinal damage significantly decreased between T0 and T1, however, without reaching values similar to controls (P < .0001). Compared with BSI-, a persistent high level of microbial translocation in the BSI+ group was observed. In the FMT+ group, markers of microbial translocation and inflammation at T1 tended to reach control values.

Conclusions: CDI is associated with high levels of microbial translocation, inflammation, and intestinal damage, which are still present at clinical resolution of CDI. The role of residual mucosal perturbation and persistence of intestinal cell damage in the development of n-BSI following CDI, as well as the possible effect of FMT in the restoration of mucosal integrity, should be further investigated.

Keywords: Clostridioides difficile infection; I-FABP; LPS; fecal microbiota transplantation; microbial translocation; nosocomial bloodstream infection.