Fig 1.
Infection with T. cruzi perturbs the fecal microbiome and metabolome.
(A) Intestinal parasite burden progression during the acute and chronic stage of the disease. Parasite signal peaked at day 35 post-infection and decreased into the chronic stage of the disease. (B, C) Principal coordinates analysis (PCoA) showing clustering of high parasite burden samples (dotted oval) compared to uninfected and low parasite burden samples for fecal microbiome (B, weighted UniFrac distance metric) and fecal metabolome (C, Bray-Curtis-Faith distance metric). Each sphere represents a single sample from one mouse at a given timepoint. Spheres are colored by intestinal parasite burden, with darkest spheres coming from samples collected at the peak of infection, when parasite burden is highest. Samples collected prior to infection are shown by large spheres, with all other samples represented by small spheres. (D,E) Random forest classification error between infected and uninfected samples using microbiome (D) and metabolome (E) datasets. Classifier is unable to distinguish between infected and uninfected samples initially. Classification accuracy improves over the acute stage of infection, with near-perfect classification 21 days post-infection. Error then increases during the chronic disease stage, although classification accuracy remains better than pre-infection.
Fig 2.
Joint microbial and chemical alterations during experimental Chagas disease.
(A) Procrustes analysis of microbiome and metabolome data, showing similar overall trends for microbiome and metabolome: lack of segregation between infected and uninfected samples at day 0, and clear separation at day 21. Less separation was observed 90 days post-infection. Connected spheres came from the same sample. Black lines indicate metabolome data and red lines microbiome data. (B) Network of correlated CLA derivatives (outer perimeter) and bacterial OTUs (central circles and V shapes), as identified by WGCNA analysis (correlation coefficients > 0, p-value <0.05). Known metabolizing bacterial genera are V-shaped, all other OTUs are represented by circles. OTU nodes are colored based on corresponding bacterial order, to highlight members of the Bacteroidales, Bifidobacteriales, Clostridiales, Lactobacillales orders. (C) Network of correlated cholic acid derivatives and bacterial OTUs, as identified by WGCNA analysis (correlation coefficients > 0, p-value <0.05). Known metabolizing bacterial genera are V-shaped, all other OTUs are represented by circles. OTU nodes are colored based on corresponding bacterial order.
Table 1.
Conjugated linoleic acid-related molecules correlated to parasite burden.
Table 2.
Cholic acid/deoxycholic acid-related molecules correlated with parasite burden.