Distinct gut metagenomics and metaproteomics signatures in prediabetics and treatment-naïve type 2 diabetics

Abstract

BackgroundThe gut microbiota plays important roles in modulating host metabolism. Previous studies have demonstrated differences in the gut microbiome of T2D and prediabetic individuals compared to healthy individuals, with distinct disease-related microbial profiles being reported in groups of different age and ethnicity. However, confounding factors such as anti-diabetic medication hamper identification of the gut microbial changes in disease development.MethodWe used a combination of in-depth metagenomics and metaproteomics analyses of faecal samples from treatment-naïve type 2 diabetic (TN-T2D, n = 77), pre-diabetic (Pre-DM, n = 80), and normal glucose tolerant (NGT, n = 97) individuals to investigate compositional and functional changes of the gut microbiota and the faecal content of microbial and host proteins in Pre-DM and treatment-naïve T2D individuals to elucidate possible host-microbial interplays characterizing different disease stages.FindingsWe observed distinct differences characterizing the gut microbiota of these three groups and validated several key features in an independent TN-T2D cohort. We also demonstrated that the content of several human antimicrobial peptides and pancreatic enzymes differed in faecal samples between three groups.InterpretationOur findings suggest a complex, disease stage-dependent interplay between the gut microbiota and the host and point to the value of metaproteomics to gain further insight into interplays between the gut microbiota and the host.FundThe study was supported by the National Natural Science Foundation of China (No. 31601073), the National Key Research and Development Program of China (No. 2017YFC0909703) and the Shenzhen Municipal Government of China (No. JCYJ20170817145809215). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Metaproteomics characterizes human gut microbiome function in colorectal cancer

“…Owing to the complexity of fecal sample, heterogeneity among samples, and the large numbers of identified proteins, no significant difference in protein abundance between the two groups could be reached with a significance cut-off of a Benjamini-Hochberg adjusted P value < 0.05. The same situation has been reported in previous metaproteomic research 20,21 . Therefore, differentially expressed proteins were determined using fold change (FC) analysis and t test.…”

Distinct human gut microbial taxonomic signatures uncovered with different sample processing and microbial cell disruption methods for metaproteomic analysis

“…Bacteria was the most abundant superkingdom in the human gut microbiome; we found that it represented 96-99% of the microbiome, consistent with previous studies (Kolmeder et al, 2016; Tanca et al, 2017). In agreement with other works (Arumugam et al, 2011; Kolmeder et al, 2012; Kolmeder et al, 2016; Tanca et al, 2017; Zhang et al, 2017; Zhong et al, 2019), the four most abundant phyla in our 6 samples were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria (Figure 3A). The dominant phylum was Firmicutes, except in S3, where Bacteroidetes was the principal phylum.…”

“…We found that the enrichment of the antimicrobial humoral response process was due to the high number of antimicrobial peptides identified in the samples, consistent with other metaproteomics studies (Zhong et al, 2019). These antimicrobial peptides, like defensin-5, lysozyme c, and phospholipase A2, accomplish important roles in the defense against bacteria (Zhong et al, 2019). Apart from antimicrobial peptides, we identified other proteins like Interlectin 1, S100A9, S100A8, and galectin 3, which are related to the antimicrobial humoral response.…”

Plasma and Urinary (Poly)phenolic Profiles after 4-Week Red Raspberry (Rubus idaeus L.) Intake with or without Fructo-Oligosaccharide Supplementation

“…The mechanisms underlying this finding are unknown. Recent studies have observed aberrant gut microbiome structure in PreDM individuals [ 16 , 17 ]. One possible explanation is individuals with PreDM have diminished microbial capacity to metabolize fruit bioactive compounds, such as (poly)phenols, to their respective bioavailable metabolites.…”