Fecal microbial load is a major determinant of gut microbiome variation and a confounder for disease associations

Suguru Nishijima, Evelina Stankevic, Oliver Aasmets, Thomas S B Schmidt, Naoyoshi Nagata, Marisa Isabell Keller, Pamela Ferretti, Helene Bæk Juel, Anthony Fullam, Shahriyar Mahdi Robbani, Christian Schudoma, Johanne Kragh Hansen, Louise Aas Holm, Mads Israelsen, Robert Schierwagen, Nikolaj Torp, Anja Telzerow, Rajna Hercog, Stefanie Kandels, Diënty H M HazenbrinkManimozhiyan Arumugam, Flemming Bendtsen, Charlotte Brøns, Cilius Esmann Fonvig, Jens-Christian Holm, Trine Nielsen, Julie Steen Pedersen, Maja Sofie Thiele, Jonel Trebicka, Elin Org, Aleksander Krag, Torben Hansen, Michael Kuhn, Peer Bork*, GALAXY and MicrobLiver Consortia

*Kontaktforfatter

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

2 Downloads (Pure)

Abstract

The microbiota in individual habitats differ in both relative composition and absolute abundance. While sequencing approaches determine the relative abundances of taxa and genes, they do not provide information on their absolute abundances. Here, we developed a machine-learning approach to predict fecal microbial loads (microbial cells per gram) solely from relative abundance data. Applying our prediction model to a large-scale metagenomic dataset (n = 34,539), we demonstrated that microbial load is the major determinant of gut microbiome variation and is associated with numerous host factors, including age, diet, and medication. We further found that for several diseases, changes in microbial load, rather than the disease condition itself, more strongly explained alterations in patients' gut microbiome. Adjusting for this effect substantially reduced the statistical significance of the majority of disease-associated species. Our analysis reveals that the fecal microbial load is a major confounder in microbiome studies, highlighting its importance for understanding microbiome variation in health and disease.

OriginalsprogEngelsk
TidsskriftCell
Vol/bind188
Udgave nummer1
Sider (fra-til)222-236.e15
ISSN0092-8674
DOI
StatusUdgivet - 9. jan. 2025

Fingeraftryk

Dyk ned i forskningsemnerne om 'Fecal microbial load is a major determinant of gut microbiome variation and a confounder for disease associations'. Sammen danner de et unikt fingeraftryk.

Citationsformater