Metaproteomics to Decipher CF Host-Microbiota Interactions: Overview, Challenges and Future Perspectives

Abstract

Cystic fibrosis (CF) is a hereditary disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, triggering dysfunction of the anion channel in several organs including the lung and gut. The main cause of morbidity and mortality is chronic infection. The microbiota is now included among the additional factors that could contribute to the exacerbation of patient symptoms, to treatment outcome, and more generally to the phenotypic variability observed in CF patients. In recent years, various omics tools have started to shed new light on microbial communities associated with CF and host-microbiota interactions. In this context, proteomics targets the key effectors of the responses from organisms, and thus their phenotypes. Recent advances are promising in terms of gaining insights into the CF microbiota and its relation with the host. This review provides an overview of the contributions made by proteomics and metaproteomics to our knowledge of the complex host-microbiota partnership in CF. Considering the strengths and weaknesses of proteomics-based approaches in profiling the microbiota in the context of other diseases, we illustrate their potential and discuss possible strategies to overcome their limitations in monitoring both the respiratory and intestinal microbiota in sample from patients with CF.

Keywords: cystic fibrosis; mass spectrometry; microbiota; proteomics.

Figure 1

Meta-omics profiling of CF microbiota. For each “omics” technology employed to characterise the respiratory or intestinal microbiota associated with CF, the aspects investigated and key contributions to the field are indicated. The colour of the dots next to each finding listed indicates the technique by which it was obtained.

Figure 2

Schematic workflow employed in metaproteomics experiments. For each one of the three main steps in the metaproteomic analysis, critical aspects that should be taken into account or carefully evaluated are highlighted.

Figure 3

Questions that could be answered using proteomics-based approaches. Sample questions that could currently be addressed by analysing airways and intestinal microbiota from CF patients using proteomics-based approaches. For the discovery proteomics, for each question described (left side), the corresponding output of the metaproteomic analysis is summarised (right side). The main steps in the experimental workflow and the widely used approaches are also highlighted. For the translational proteomics, the main approaches are indicated alongside with their output.