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Review
. 2021 Feb 12;9(2):371.
doi: 10.3390/microorganisms9020371.

Contribution of Inhibitory Metabolites and Competition for Nutrients to Colonization Resistance against Clostridioides difficile by Commensal Clostridium

Amber D Reed  1 , Casey M Theriot  1
Affiliations
Review

Contribution of Inhibitory Metabolites and Competition for Nutrients to Colonization Resistance against Clostridioides difficile by Commensal Clostridium

Amber D Reed et al. Microorganisms. .

Abstract

Clostridioides difficile is an anaerobic pathogen that causes significant morbidity and mortality. Understanding the mechanisms of colonization resistance against C. difficile is important for elucidating the mechanisms by which C. difficile is able to colonize the gut after antibiotics. Commensal Clostridium play a key role in colonization resistance. They are able to modify bile acids which alter the C. difficile life cycle. Commensal Clostridium also produce other inhibitory metabolites including antimicrobials and short chain fatty acids. They also compete with C. difficile for vital nutrients such as proline. Understanding the mechanistic effects that these metabolites have on C. difficile and other gut pathogens is important for the development of new therapeutics against C. difficile infection (CDI), which are urgently needed.

Keywords: Clostridioides difficile; Clostridium scindens; deconjugation; dehydroxylation; epimerization; hydroxyproline; proline; secondary bile acids; short-chain fatty acids.

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Conflict of interest statement

CMT is a consultant for Vedanta Biosciences and Summit Therapeutics.

Figures

Figure 1
Figure 1
Selected transformations of bile acids carried out by gut bacteria and their effect on Clostridioides difficile. TCA is a strong germinant for C. difficile spores and TCDCA is a weak germinant. CA is a moderate germinant for C. difficile spores, and CDCA inhibits vegetative C. difficile. The secondary bile acids DCA and LCA inhibit vegetative C. difficile and iDCA and iLCA strongly inhibit C. difficile. Abb. BSH, bile salt hydrolase; bai, bile acid inducible; HSDH, hydroxysteroid dehydrogenase; TCA, taurocholate; TCDCA, taurochenodeoxycholate; CA, cholate; CDCA, chenodeoxycholate; DCA, deoxycholate; LCA, lithocholate; iDCA, isodeoxycholate; iLCA, isolithocholate. Created with BioRender.com.
Figure 2
Figure 2
Proposed pathway for conversion from CA to DCA via 7α-dehydroxylation. This metabolic pathway converts CA to DCA or converts CDCA to LCA in eight steps. Abb. BaiB, bile acid-coenzyme A ligase; BaiA2, 3α-hydroxysteroid dehydrogenase; BaiCD, 7α-hydroxy-3-oxo-Δ4-cholenoic acid oxidoreductase; BaiE, bile acid 7α-dehydratase; BaiF, bile acid coenzyme A transferase/hydrolase; BaiH, 7β -hydroxy-3-oxo-Δ4-cholenoic acid oxidoreductase; CA, cholate; DCA, deoxycholate.
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