Analysis of the intestinal microbial community and inferred functional capacities during the host response to <i>Pneumocystis</i> pneumonia

<b>Background:</b><i>Pneumocystis</i> pneumonia is a major cause of morbidity and mortality in patients infected with HIV/AIDS. In this study, we evaluated the intestinal microbial communities associated with the development of experimental <i>Pneumocystis</i> pneumonia, as there is growing evidence that the intestinal microbiota is critical for host defense against fungal pathogens. <b>Methods:</b> C57BL/6 mice were infected with live <i>Pneumocystis murina</i> (<i>P. murina</i>) via intratracheal inoculation and sacrificed 7 and 14 days postinfection for microbiota analysis. In addition, we evaluated the intestinal microbiota from CD4+ T cell depleted mice infected with <i>P. murina</i>. <b>Results:</b> We found that the diversity of the intestinal microbial community was significantly altered by respiratory infection with <i>P. murina</i>. Specifically, mice infected with <i>P. murina</i> had altered microbial populations, as judged by changes in diversity metrics and relative taxa abundances. We also found that CD4+ T cell depleted mice infected with <i>P. murina</i> exhibited significantly altered intestinal microbiota that was distinct from immunocompetent mice infected with <i>P. murina</i>, suggesting that loss of CD4+ T cells may also affects the intestinal microbiota in the setting of <i>Pneumocystis</i> pneumonia. Finally, we employed a predictive metagenomics approach to evaluate various microbial features. We found that <i>Pneumocystis</i> pneumonia significantly alters the intestinal microbiota's inferred functional potential for carbohydrate, energy, and xenobiotic metabolism, as well as signal transduction pathways. <b>Conclusions:</b> Our study provides insight into specific-microbial clades and inferred microbial functional pathways associated with <i>Pneumocystis</i> pneumonia. Our data also suggest a role for the gut-lung axis in host defense in the lung.