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2015 ; 9
(9
): 1908-15
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Monitoring host responses to the gut microbiota
#MMPMID26057846
Lichtman JS
; Sonnenburg JL
; Elias JE
ISME J
2015[Sep]; 9
(9
): 1908-15
PMID26057846
show ga
The gastrointestinal (GI) ecosystem is increasingly understood to be a
fundamental component of health, and has been identified as a new focal point for
diagnosing, correcting and preventing countless disorders. Shotgun DNA sequencing
has emerged as the dominant technology for determining the genetic and microbial
composition of the gut microbiota. This technology has linked microbiota
dysbioses to numerous GI diseases including inflammatory bowel disease, obesity
and allergy, and to non-GI diseases like autism and depression. The importance of
establishing causality in the deterioration of the host-microbiota relationship
is well appreciated; however, discovery of candidate molecules and pathways that
underlie mechanisms remains a major challenge. Targeted approaches,
transcriptional assays, cytokine panels and imaging analyses, applied to animals,
have yielded important insight into host responses to the microbiota. However,
non-invasive, hypothesis-independent means of measuring host responses in humans
are necessary to keep pace with similarly unbiased sequencing efforts that
monitor microbes. Mass spectrometry-based proteomics has served this purpose in
many other fields, but stool proteins exist in such diversity and dynamic range
as to overwhelm conventional proteomics technologies. Focused analysis of host
protein secretion into the gut lumen and monitoring proteome-level dynamics in
stool provides a tractable route toward non-invasively evaluating dietary,
microbial, surgical or pharmacological intervention efficacies. This review is
intended to guide GI biologists and clinicians through the methods currently used
to elucidate host responses in the gut, with a specific focus on mass
spectrometry-based shotgun proteomics applied to the study of host protein
dynamics within the GI ecosystem.
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