Exploring Protein Functions of Gut Bacteriome and Mycobiome in Thai Infants Associated with Atopic Dermatitis Through Metaproteomic and Host Interaction Analysis

Abstract

Atopic dermatitis (AD), a prevalent allergic skin condition in children, has been closely associated with imbalances in the gut microbiome. To investigate these microbial alterations and their functional implications, we investigated protein expression, functions and interactions of the gut bacteriome and mycobiome as well as the human proteome in Thai infants with AD using integrative metaproteomic and host interaction analysis. As we observed, probiotic species, such as Lactobacillus acidophilus and Bacteroides salyersiae, were reduced in abundance in the AD group while key pathogenic bacteria and fungi, such as Streptococcus constellatus and Penicillium chrysogenum, increased in abundance. Additionally, the functional analysis of expressed proteins was enriched in response to stress and DNA repair in the bacteriome and ribosome biogenesis-related processes in the mycobiome of the AD group, potentially associated to increased reactive oxygen species (ROS), intestinal inflammation, fungal growth and microbial dysbiosis. Further, a protein-protein interactions (PPIs) network analysis incorporating the human proteome revealed 10 signature proteins related to stress and immune system processes associated with AD. Our findings propose the interactions of the key species and signature protein functions between the gut microbes and the human host in response to AD in Thai infants. To our knowledge, this study serves as the first framework for monitoring bacteriome-mycobiome-human gut studies associated with AD and other allergic diseases in infants.

Keywords: atopic dermatitis; human gut; metaproteomics; microbiome; mycobiome.

Figure 1

The most predominant (a) bacterial and (b) fungal taxa in Thai infant guts of healthy and AD groups. Note: Blue color indicates a greater presence of microbial taxa while yellow color indicates less presence of microbial taxa.

Figure 2

Microbial composition profiles between healthy and AD groups for (a) bacterial families and (b) fungal genera.

Figure 3

Alpha and beta diversity comparisons of gut microbiome between healthy (H) and AD groups. Boxplot shows alpha diversity indices (a,b) Shannon’s and Simpson’s for the bacteriome, respectively, and (c,d) Shannon’s and Simpson’s for the mycobiome between H (blue) and AD (red) groups. Principal coordinate analysis (PCoA) plots display beta diversity based on Bray–Curtis distance for (e) the bacteriome and (f) the mycobiome studies.

Figure 4

Heat map showing the relative abundance of key species associated with AD. Note: The data are log2-transformed and normalized to z-scores. Green represents reduced abundance while red indicates increased abundance. Hierarchical clustering shows a clear separation between the two groups. Each row in the heatmap represents a microbial species, classified as either bacterial (B) or fungal (F), and each column corresponds to an individual sample.

Figure 5

DEP analysis between healthy (H) and AD groups. Volcano plot depicts DEPs in (a) bacterial metaproteomics, (b) fungal metaproteomics and (c) human proteomics, respectively (red color: upregulated proteins in AD; blue color: downregulated proteins in AD; grey color: no significance). (d–f) Mirrored bar plot represents the frequency of DEPs classified by COG terms in (d) the bacteriome, (e) mycobiome and (f) human (red color: upregulated proteins in AD; blue color: downregulated proteins in AD). (g) List of COG categories and their functional terms.

Figure 6

Functional enrichment analysis of upregulated proteins under the bacteriome and mycobiome datasets (FDR < 0.05). (a) Bubble plot shows 12 significantly enriched GO biological processes in the bacteriome. (b) Bubble plot shows 2 significantly enriched GO biological processes in the mycobiome. The x-axis represents fold enrichment while bubble color indicates -log10(FDR) and bubble size represents protein count.

Figure 7

Protein–protein interactions (PPIs) network of significant proteins associated with AD. Node sizes are proportional to statistical significance, e.g., large node stands for high significance protein (low p-value) and small node stands for low significance protein (high p-value). The color of each node reflects the log2 fold change in the corresponding protein. Red node means upregulated protein and blue node means downregulated protein in AD group. The edge and edge thickness represent pairwise interactions (PIs) between proteins and strength of PIs within the network.

Figure 8

A proposed interaction of key species (arrows pointing up indicate species increased in AD, while arrows pointing down indicate species reduced in AD) and signature protein functions between gut microbes and human host in response to AD in Thai infants.

Figure 9

Holistic workflow of protein expression and function of the gut bacteriome and mycobiome in Thai infants associated with AD through metaproteomic and interaction analysis [11].