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. Author manuscript; available in PMC: 2016 Oct 5.
Published in final edited form as: Anaerobe. 2016 May 7;41:44–50. doi: 10.1016/j.anaerobe.2016.05.003

Table 2.

The impact of secondary bile acids on the life cycle of C. difficile using ex vivo and in vivo approaches.

Host Antibiotic
treatment		 Bile acid analysis Main findings of the study Strain
(ribotype)		 Ref.
Ex vivo studies
CD-1
female mice		 Clindamycin Measure NADH
during oxidation of
hydroxyl groups of
bile salts by HSDHs		 Able to stimulate a high level of colony formation from spores in antibiotic treated
mouse cecal contents, made up of primary bile acids and a reduction in secondary bile
acids.		 CD196
(027) 		64
5–14 wk C57BL/6
WT male and
female mice (colony
established from Jax)		 Cefoperazone Untargeted and
targeted bile acid LC-
MS assay (limited
bile acids library)		 Cecal content of mice after antibiotics had a decrease in secondary bile acid DCA and
increased primary bile acids, TCA and CA, and allowed for spore germination and
outgrowth and growth of vegetative cells. No spore germination and outgrowth was
seen in mouse cecal content prior to antibiotics.		 VPI 10463
(003)
BI-9
(027) 		11
See above Cefoperazone Targeted bile acid
LC-MS assay
(expanded bile acid
library)		 Cecal content of mice prior to antibiotic treatment contained higher concentrations of
secondary bile acids, including DCA, UDCA, LCA and ωMCA.
Inhibition of spore germination and outgrowth was seen in cecal content.		 VPI 10463
(003) 		65
See above
  • -

    Cefoperazone plus 1–6 wk period off

  • -

    Clindamycin

  • -

    Vancomycin

  • -

    Metronidazole

  • -

    Kanamycin

 Targeted bile acid
LC-MS assay
(expanded bile acid
library)		 Cecal content that provided resistance against spore germination and outgrowth had
an average concentration of secondary bile acids: ωMCA 0.004%, HDCA 0.002%,
UDCA 0.004%, LCA 0.001%, and DCA 0.023%.
Cecal content that allowed for susceptibility to spore germination and outgrowth
showed a significant loss in the secondary bile acids listed above and increased TCA.		 VPI 10463
(003) 		50
In vivo studies
5–14 wk C57BL/6
WT male and
female mice (colony
established from Jax)		 Cefoperazone Targeted bile acid
LC-MS assay
(expanded bile acid
library)		 Susceptibility to C. difficile colonization in mice was associated with significant
changes to the gut metabolome, specifically a decrease in secondary bile acid DCA
and an increase in primary bile acid TCA.		 VPI 10463
(003) 		11
Fecal transplant
patients and donors		 LC-MS assay Increased fecal DCA and LCA were associated with recovery from C. difficile
infection in post-FMT patients.		 NAP1
(027) 		17
6–8 wk
C57BL/6J female
mice from Jax		 Combination of
kanamycin,
gentamycin, colistin,
metronidazole,
vancomycin in
followed by single
dose of clindamycin		 LC-MS assay C. scindens alone and in concert with three other bacteria restored partial colonization
resistance against C. difficile in mice. This was associated with restored relative
abundance of secondary bile acids DCA and LCA in the cecum and no changes in
primary bile acid relative abundance.		 VPI 10463
(003) 		12
CDI Relapse
patient		 LC-MS assay Oral therapy of UDCA prevents relapse of C. difficile infection in a patient with ileal
pouchitis (n=1).		 NAP1
(027) 		22

Abbreviations: HSDH: Hydroxysteroid dehydrogenases; LC-MS: Liquid chromatography–mass spectrometry