Host and Clostridioides difficile-Response Modulated by Micronutrients and Glutamine: An Overview

Abstract

Changes in intestinal microbiota are integral to development of Clostridioides difficile (C. difficile)—associated nosocomial diarrhea. Certain diets, especially Western diets, increase susceptibility to C. difficile infection (CDI). Here, we discuss recent findings regarding how nutrients modulate response of the host and C. difficile during infection. Calcium has a role in the sporulation and germination process. Selenium is effective in reducing the total amount of C. difficile toxin A (TcdA) and toxin B (TcdB) and in decreasing its cytotoxicity. In addition, selenium phosphate synthetase deficiency reduces C. difficile growth and spore production. On the other hand, iron has a dual role in C. difficile growth. For instance, high intracellular levels can generate reactive hydroxyl radicals, whereas low levels can reduce its growth. In humans, zinc deficiency appears to be related to the recurrence of CDI, in contrast, in the CDI model in mice a diet rich in zinc increased the toxin's activity. Low vitamin D levels contribute to C. difficile colonization, toxin production, and inflammation. Furthermore, glutamine appears to protect intestinal epithelial cells from the deleterious effects of TcdA and TcdB. In conclusion, nutrients play an important role in modulating host and pathogen response. However, further studies are needed to better understand the mechanisms and address some controversies.

Rapid discrimination between clinical Clostridioides difficile infection and colonization by quantitative detection of TcdB toxin using a real-time cell analysis system

“…It has been reported that bile acids ( Tam et al, 2020 ), short-chain fatty acids ( Yuille et al, 2015 ), and the trace element selenium ( Loureiro et al, 2022 ) were considered potential inhibitors of TcdB-induced cytotoxicity, however the reports on fecal TcdB inhibitors are limited. Our study showed that significant differences in functional and toxical TcdB levels were observed between patients with CDC and CDI, while their total levels of TcdB protein were comparable.…”

Role of the Alteration in Calcium Homeostasis in Cell Death Induced by Clostridioides difficile Toxin A and Toxin B

“…Loureiro et al [ 146 ] analyzed the modulation of response of host and C. difficile by nutrients, including Ca 2+ , that play a key role in sporulation and germination of C. difficile in the gut [ 146 ], reporting that there was only one recent paper describing a role of Ca 2+ in vitro [ 82 ] and that no reports on Ca 2+ uptake or serum Ca 2+ levels in CDI in patients or murine models.…”