Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals

Authors: ASNICAR, FRANCESCO - University Of Trento, Italy; BERRY, SARAH - King'S College; VALDES, ANA - University Of Nottingham; NGUYEN, LONG - Harvard University; PICCINNO, GIANMARCO - University Of Trento, Italy; DREW, DAVID - Harvard University; LEEMING, EMILY - King'S College; GIBSON, RACHEL - King'S College; LE ROY, CAROLINE - King'S College; KHATIB, HAYA - Zoe Global Limited; FRANCIS, LUCY - Zoe Global Limited; MAZIDI, MOHSEN - King'S College; MOMPEO, OLATZ - King'S College; VALLES-COLOMER, MIREIA - University Of Trento, Italy; TETT, ADRIAN - University Of Trento, Italy; BEGHINI, FRANCESCO - University Of Trento, Italy; DUBOIS, LEONARD - University Of Trento, Italy; BAZZANI, DAVIDE - University Of Trento, Italy; THOMAS, ANDREW - University Of Trento, Italy; MIRZAYI, CHLOE - City University Of New York; KHLEBORODOVA, ASYA - City University Of New York; OH, SEHYUN - City University Of New York; HINE, RACHEL - Zoe Global Limited; BONNETT, CHRISTOPHER - Zoe Global Limited; CAPDEVILA, JOAN - Zoe Global Limited; DANZANVILLIERS, SERGE - Zoe Global Limited; GIORDANO, FRANCESCA - Zoe Global Limited; GEISTLINGER, LUDWIG - City University Of New York; WALDRON, LEVI - City University Of New York; DAVIES, RICHARD - Zoe Global Limited; HADJIGEORGIOU, GEORGE - Zoe Global Limited; WOLF, JONATHAN - Zoe Global Limited; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; GARDNER, CHRISTOPHER - Stanford University; FRANKS, PAUL - Lund University; CHAN, ANDREW - Harvard University; HUTTENHOWER, CURTIS - Harvard University; SPECTOR, TIM - King'S College; SEGATA, NICOLA - University Of Trento, Italy

Submitted to: Nature Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/16/2020
Publication Date: 1/11/2021
Citation: Asnicar, F., Berry, S.E., Valdes, A.M., Nguyen, L.H., Piccinno, G., Drew, D.A., Leeming, E., Gibson, R., Le Roy, C., Khatib, H.A., Francis, L., Mazidi, M., Mompeo, O., Valles-Colomer, M., Tett, A., Beghini, F., Dubois, L., Bazzani, D., Thomas, A., Mirzayi, C., Khleborodova, A., Oh, S., Hine, R., Bonnett, C., Capdevila, J., Danzanvilliers, S., Giordano, F., Geistlinger, L., Waldron, L., Davies, R., Hadjigeorgiou, G., Wolf, J., Ordovas, J.M., Gardner, C.D., Franks, P.W., Chan, A., Huttenhower, C., Spector, T.D., Segata, N. 2021. Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals. Nature Medicine. 27:321-332. https://doi.org/10.1038/s41591-020-01183-8.
DOI: https://doi.org/10.1038/s41591-020-01183-8

Interpretive Summary: The human microbiota consists of the 10-100 trillion microbial cells each person harbors, primarily bacteria in the gut; the human microbiome consists of the genes these cells harbor. The gut microbiome is shaped by diet and influences human metabolism; however, these links are complex and unique to each individual. The purpose of this work, conducted by an international team including investigators at the HNRCA in Boston, was to deeply characterize 1,203 gut microbiomes from 1,098 individuals enrolled in the Personalized Responses to Dietary Composition Trial (PREDICT 1) study. The analyses revealed significant associations between microbes and specific nutrients and foods, driven primarily by the presence and diversity of healthy and plant-based foods. The panel of intestinal species associated with healthy dietary habits overlapped with favorable cardiometabolic and postprandial markers, indicating that this large-scale resource can identify good and bad microbes in individuals without clinically manifest disease and provide healthy dietary advice to prevent chronic diseases.

Technical Abstract: The gut microbiome is shaped by diet and influences host metabolism; however, these links are complex and can be unique to each individual. We performed deep metagenomic sequencing of 1,203 gut microbiomes from 1,098 individuals enrolled in the Personalised Responses to Dietary Composition Trial (PREDICT 1) study, whose detailed long-term diet information, as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements were available. We found many significant associations between microbes and specific nutrients, foods, food groups and general dietary indices, which were driven especially by the presence and diversity of healthy and plant-based foods. Microbial biomarkers of obesity were reproducible across external publicly available cohorts and in agreement with circulating blood metabolites that are indicators of cardiovascular disease risk. While some microbes, such as Prevotella copri and Blastocystis spp., were indicators of favorable postprandial glucose metabolism, overall microbiome composition was predictive for a large panel of cardiometabolic blood markers including fasting and postprandial glycemic, lipemic and inflammatory indices. The panel of intestinal species associated with healthy dietary habits overlapped with those associated with favorable cardiometabolic and postprandial markers, indicating that our large-scale resource can potentially stratify the gut microbiome into generalizable health levels in individuals without clinically manifest disease.