Increased Urinary Trimethylamine N-Oxide Following Cryptosporidium Infection and Protein Malnutrition Independent of Microbiome Effects

J Infect Dis. 2017 Jul 1;216(1):64-71. doi: 10.1093/infdis/jix234.


Cryptosporidium infections have been associated with growth stunting, even in the absence of diarrhea. Having previously detailed the effects of protein deficiency on both microbiome and metabolome in this model, we now describe the specific gut microbial and biochemical effects of Cryptosporidium infection. Protein-deficient mice were infected with Cryptosporidium parvum oocysts for 6-13 days and compared with uninfected controls. Following infection, there was an increase in the urinary excretion of choline- and amino-acid-derived metabolites. Conversely, infection reduced the excretion of the microbial-host cometabolite (3-hydroxyphenyl)propionate-sulfate and disrupted metabolites involved in the tricarboxylic acid (TCA) cycle. Correlation analysis of microbial and biochemical profiles resulted in associations between various microbiota members and TCA cycle metabolites, as well as some microbial-specific degradation products. However, no correlation was observed between the majority of the infection-associated metabolites and the fecal bacteria, suggesting that these biochemical perturbations are independent of concurrent changes in the relative abundance of members of the microbiota. We conclude that cryptosporidial infection in protein-deficient mice can mimic some metabolic changes seen in malnourished children and may help elucidate our understanding of long-term metabolic consequences of early childhood enteric infections.

Keywords: Cryptosporidium; choline; malnutrition; metabonome; microbiome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / urine
  • Citric Acid Cycle
  • Cryptosporidiosis / diagnosis
  • Cryptosporidiosis / microbiology
  • Cryptosporidiosis / urine*
  • Cryptosporidium parvum / isolation & purification
  • Feces / microbiology
  • Gastrointestinal Microbiome*
  • Lipocalin-2 / genetics
  • Lipocalin-2 / metabolism
  • Male
  • Metabolome
  • Methylamines / urine*
  • Mice
  • Mice, Inbred Strains
  • Peroxidase / genetics
  • Peroxidase / metabolism
  • Protein-Energy Malnutrition / microbiology
  • Protein-Energy Malnutrition / urine*
  • Up-Regulation


  • Biomarkers
  • Lipocalin-2
  • Methylamines
  • Lcn2 protein, mouse
  • Peroxidase
  • trimethyloxamine