Abstract
Gut microbiota and the host exist in a mutualistic relationship, with the functional composition of the microbiota strongly influencing the health and well-being of the host. In addition to the standard differential expression analysis of host genes to assess the complex cross-talk between environment (diet), microbiome, and host intestinal physiology, data-driven integrative approaches are needed to identify potential biomarkers of both host genes and microbial communities that characterize these interactions. Our findings demonstrate that the complementary application of univariate differential gene expression analysis and multivariate approaches such as sparse Canonical Correlation Analysis (sCCA) and sparse Principal Components Analysis (sPCA) can be used to integrate data from both the healthy infant gut microbial community and host transcriptome (exfoliome) using stool derived exfoliated cells shed from the gut. These approaches reveal host genes and microbial functional categories related to the feeding phenotype of the infants. Our findings also confirm that combinatorial noninvasive -omic approaches provide an integrative genomics-based perspective of neonatal host-gut microbiome interactions.
Highlights
Microbial colonization in infants is critically important for directing neonatal intestinal and immune development and is especially attractive for studying the development of human-commensal interactions [1,2]
Analysis of VFA concentrations in feces demonstrated differences in both short-chain fatty acids (SCFA) and branched-chain fatty acids (BCFA) between BF and FF infants (Table 1). Alterations in these microbial metabolites could be explained by differences in fermentable substrates in human milk vs. formula, microbial populations or diet-induced differences in the expression of host genes associated with host short chain fatty acids (SCFA) uptake and metabolism
We applied both univariate analysis of differential gene expression and multivariate sparse Principal Components Analysis (sPCA) and sparse Canonical Correlation Analysis (sCCA) to genes associated with SCFA receptor signaling
Summary
Microbial colonization in infants is critically important for directing neonatal intestinal and immune development and is especially attractive for studying the development of human-commensal interactions [1,2]. It is imperative to understand the adaptive responses of the neonatal gut to diet, the intestinal microbiome, and microbial metabolites. Access to tissue biopsies from healthy human infants is impossible, our group has previously established and validated a methodology using stool derived exfoliated cells from the gut to interrogate the responses of the neonatal intestinal global transcriptome, i.e., exfoliome, to dietary substrates in the early neonatal period [3,4]. Each day, ~10 billion cells are exfoliated from the intestinal lining as part of normal epithelial cell turnover [5]. Exfoliated cells in stool have been used in children with inflammatory bowel disease [9] and in stool [8] and gastric aspirates of preterm infants [10] to study cellular and molecular markers
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