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Fecal Indole as a Biomarker of Susceptibility to Cryptosporidium Infection - PubMed

  • ️Fri Jan 01 2016

Fecal Indole as a Biomarker of Susceptibility to Cryptosporidium Infection

Cynthia L Chappell et al. Infect Immun. 2016.

Abstract

Cryptosporidium causes significant diarrhea worldwide, especially among children and immunocompromised individuals, and no effective drug treatment is currently available for those who need it most. In this report, previous volunteer infectivity studies have been extended to examine the association between fecal indole and indole-producing (IP) gut microbiota on the outcome of a Cryptosporidium infection. Fecal indole concentrations (FICs) of 50 subjects and 19 taxa of common gut microbiota, including six IP taxa (11 subjects) were determined in stool samples collected before and after a challenge with Cryptosporidium oocysts. At the baseline, the mean FIC (± the standard deviation) was 1.66 ± 0.80 mM in those who became infected after a challenge versus 3.20 ± 1.23 mM in those who remained uninfected (P = 0.0001). Only 11.1% of the subjects with a FIC of >2.5 mM became infected after a challenge versus 65.2% of the subjects with a FIC of <2.5 mM. In contrast, the FICs of infected subjects at the baseline or during diarrhea were not correlated with infection intensity or disease severity. The relative abundances (percent) of Escherichia coli, Bacillus spp., and Clostridium spp. were greater ≥2.5-fold in volunteers with a baseline FIC of >2.5 mM, while those of Bacteroides pyogenes, B. fragilis, and Akkermansia muciniphila were greater in those with a baseline FIC of <2.5 mM. These data indicate that some IP bacteria, or perhaps indole alone, can influence the ability of Cryptosporidium to establish an infection. Thus, preexisting indole levels in the gut join the oocyst dose and immune status as important factors that determine the outcome of Cryptosporidium exposure.

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Figures

FIG 1
FIG 1

FICs in healthy adults at stage 1 (before or within 48 h of a challenge) and outcomes of a challenge with Cryptosporidium oocysts. (A) Cumulative percent infection was calculated as described previously (40) and plotted against the mean indole concentration. The number of subjects at each indole concentration stratum is in parentheses. (B) The indole concentrations and outcome categories of the subjects are shown. The mean indole concentration ± the standard error of the mean are indicated for the infected (oocysts plus diarrhea; n = 18) and uninfected (no oocysts or diarrhea; n = 32) challenge outcome groups. Outcome groups were compared by using the Mann-Whitney test (P = 0.0001).

FIG 2
FIG 2

Fecal bacteria associated with protection from Cryptosporidium infection. Species with ≥2.5-fold difference in %RA are shown. Stool samples from healthy adults were collected prior to (or within 48 h of) exposure to Cryptosporidium oocysts. The median %RAs of the infected (Inf; n = 6) and uninfected (Uninf; n = 5) outcome groups are shown. IP bacteria include those in panels A and B.

FIG 3
FIG 3

Fecal bacteria associated with susceptibility to Cryptosporidium infection. Species with ≥2.5-fold difference in %RA are shown. Stool samples from healthy adults were collected prior to (or within 48 h of) exposure to Cryptosporidium oocysts. The median %RAs of the infected (Inf; n = 6) and uninfected (Uninf; n = 5) outcome groups are shown. IP bacteria include those in panels A to C.

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