Regional variation limits applications of healthy gut microbiome reference ranges and disease models

Nature Medicine
Yan HeHong-Wei Zhou

Abstract

Dysbiosis, departure of the gut microbiome from a healthy state, has been suggested to be a powerful biomarker of disease incidence and progression1-3. Diagnostic applications have been proposed for inflammatory bowel disease diagnosis and prognosis4, colorectal cancer prescreening5 and therapeutic choices in melanoma6. Noninvasive sampling could facilitate large-scale public health applications, including early diagnosis and risk assessment in metabolic7 and cardiovascular diseases8. To understand the generalizability of microbiota-based diagnostic models of metabolic disease, we characterized the gut microbiota of 7,009 individuals from 14 districts within 1 province in China. Among phenotypes, host location showed the strongest associations with microbiota variations. Microbiota-based metabolic disease models developed in one location failed when used elsewhere, suggesting that such models cannot be extrapolated. Interpolated models performed much better, especially in diseases with obvious microbiota-related characteristics. Interpolation efficiency decreased as geographic scale increased, indicating a need to build localized baseline and disease models to predict metabolic risks.

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Datasets Mentioned

BETA
PRJEB18535

Methods Mentioned

BETA
PCR
Electrophoresis

Software Mentioned

Procrustes
Barcrawl
MaAsLin
SeqPrep
PERMDISP
vegan
Covaris
Adonis
envfit
R

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