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Depression phenotype identified by using single nucleotide exact amplicon sequence variants of the human gut microbiome

Abstract

Single nucleotide exact amplicon sequence variants (ASV) of the human gut microbiome were used to evaluate if individuals with a depression phenotype (DEPR) could be identified from healthy reference subjects (NODEP). Microbial DNA in stool samples obtained from 40 subjects were characterized using high throughput microbiome sequence data processed via DADA2 error correction combined with PIME machine-learning de-noising and taxa binning/parsing of prevalent ASVs at the single nucleotide level of resolution. Application of ALDEx2 differential abundance analysis with assessed effect sizes and stringent PICRUSt2 predicted metabolic pathways. This multivariate machine-learning approach significantly differentiated DEPR (n = 20) vs. NODEP (n = 20) (PERMANOVA P < 0.001) based on microbiome taxa clustering and neurocircuit-relevant metabolic pathway network analysis for GABA, butyrate, glutamate, monoamines, monosaturated fatty acids, and inflammasome components. Gut microbiome dysbiosis using ASV prevalence data may offer the diagnostic potential of using human metaorganism biomarkers to identify individuals with a depression phenotype.

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Fig. 1: ASV prevalences and metadata analyses.
Fig. 2: ASV and taxa prevalences for DEPR vs. NODEP.
Fig. 3: Metabolic pathway segregation of DEPR vs. NODEP.

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Code availability

PIME is available at https://rdrr.io/github/microEcology/pime/; DADA2 is available at https://www.bioconductor.org/packages/release/bioc/html/dada2.html; ALDEx2 is at https://bioconductor.org/packages/release/bioc/html/ALDEx2.html; and picrust2 is at https://github.com/picrust/picrust2.

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Acknowledgements

We thank Seungbum Kim and Elaine Richards for useful discussions. This study was supported by University of Florida Clinical and Translational Science Institute grant (BRS, CJP) from the National Center For Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR, 427; National Institute of Health (NIH) grants HL33610, HL56921 (MKR, CJP); UM1 HL087366 (CJP); Gatorade Trust through funds distributed by the University of Florida, Department of Medicine (CJP); PCORI-OneFlorida Clinical Research Consortium CDRN-1501–26692 (CJP); and internal funds from the University of Florida Department of Physiology and Functional Genomics (BRS, MKR).

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Stevens, B.R., Roesch, L., Thiago, P. et al. Depression phenotype identified by using single nucleotide exact amplicon sequence variants of the human gut microbiome. Mol Psychiatry 26, 4277–4287 (2021). https://doi.org/10.1038/s41380-020-0652-5

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