Environmental factors shaping the gut microbiome in a Dutch population
Gacesa , Ranko; Kurilshikov, Alexander; Vich Vila, Arnau; Sinha, Trishla; Klaassen, M; Bolte, L.A.; Andreu-Sánchez, S.; Chen, L.; Collij, V.; Hu, S.; Dekens-Konter, J.A.M.; Lenters, Virissa; Björk, J.R.; Swarte, J.C.; Swertz, Morris A.; Jansen, B.H.R.; Gelderloos-Arends, J.; Jankipersadsing, Soesma A; Hofker, M.; Vermeulen, Roel; Sanna, S.; Harmsen, H J M; Wijmenga, Cisca; Fu, J.; Zhernakova, A.; Weersma, Rinse K.
(2022) Nature, volume 604, pp. 732 - 739
(Article)
Abstract
The gut microbiome is associated with diverse diseases1–3, but a universal signature of a healthy or unhealthy microbiome has not been identified, and there is a need to understand how genetics, exposome, lifestyle and diet shape the microbiome in health and disease. Here we profiled bacterial composition, function, antibiotic resistance
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and virulence factors in the gut microbiomes of 8,208 Dutch individuals from a three-generational cohort comprising 2,756 families. We correlated these to 241 host and environmental factors, including physical and mental health, use of medication, diet, socioeconomic factors and childhood and current exposome. We identify that the microbiome is shaped primarily by the environment and cohabitation. Only around 6.6% of taxa are heritable, whereas the variance of around 48.6% of taxa is significantly explained by cohabitation. By identifying 2,856 associations between the microbiome and health, we find that seemingly unrelated diseases share a common microbiome signature that is independent of comorbidities. Furthermore, we identify 7,519 associations between microbiome features and diet, socioeconomics and early life and current exposome, with numerous early-life and current factors being significantly associated with microbiome function and composition. Overall, this study provides a comprehensive overview of gut microbiome and the underlying impact of heritability and exposures that will facilitate future development of microbiome-targeted therapies.
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Keywords: Taverne
ISSN: 0028-0836
Publisher: Nature Research
Note: Funding Information: We acknowledge and thank the late M. Hofker who initiated the Lifelines DAG3/Dutch Microbiome Project. We acknowledge the services of Lifelines Cohort Study, the contributing research centres delivering data to Lifelines and all the study participants. The Lifelines Biobank initiative has been made possible by subsidies from the Dutch Ministry of Health, Welfare and Sport, the Dutch Ministry of Economic Affairs, the University Medical Center Groningen (UMCG the Netherlands), the University of Groningen and the Northern Provinces of the Netherlands. We thank the Center for Information Technology of the University of Groningen (RUG) for their support and for providing access to the Peregrine high performance computing cluster, the Genomics Coordination Center (UMCG and RUG) for their support and for providing access to Calculon and Boxy high-performance computing clusters and the MOLGENIS team for data management and analysis support. Metagenomics library preparation and sequencing was done at Novogene. We also thank K. Mc Intyre for English and content editing and Tania Ballve Fernandez for illustration of Fig. . Sequencing of the cohort was funded by a grant from CardioVasculair Onderzoek Nederland (CVON 2012-03) to M.H., J.F. and A.Z. R.G., H.J.M.H. and R.K.W. are supported by the collaborative TIMID project (LSHM18057-SGF) financed by the PPP allowance made available by Top Sector Life Sciences & Health to Samenwerkende Gezondheidsfondsen (SGF) to stimulate public–private partnerships and co-financed by health foundations that are part of the SGF. R.K.W. is supported by the Seerave Foundation and the Dutch Digestive Foundation (16-14). A.Z. is supported by European Research Council (ERC) Starting Grant 715772, Netherlands Organization for Scientific Research (NWO) VIDI grant 016.178.056, CVON grant 2018-27 and NWO Gravitation grant ExposomeNL 024.004.017. JF is supported by the Dutch Heart Foundation IN-CONTROL (CVON2018-27), the ERC Consolidator grant (grant agreement No. 101001678), NWO-VICI grant VI.C.202.022, and the Netherlands Organ-on-Chip Initiative, an NWO Gravitation project (024.003.001) funded by the Ministry of Education, Culture and Science of the government of The Netherlands. C.W. is further supported by an ERC advanced grant (ERC-671274) and an NWO Spinoza award (NWO SPI 92-266). L.C. is supported by a joint fellowship from the University Medical Center Groningen and China Scholarship Council (CSC201708320268) and a Foundation De Cock-Hadders grant (20:20-13). M.A.S. is supported by NWO VIDI grant 016 and EUCAN-connect, a project funded by European Commission H2020 grant 824989. Funding Information: We acknowledge and thank the late M. Hofker who initiated the Lifelines DAG3/Dutch Microbiome Project. We acknowledge the services of Lifelines Cohort Study, the contributing research centres delivering data to Lifelines and all the study participants. The Lifelines Biobank initiative has been made possible by subsidies from the Dutch Ministry of Health, Welfare and Sport, the Dutch Ministry of Economic Affairs, the University Medical Center Groningen (UMCG the Netherlands), the University of Groningen and the Northern Provinces of the Netherlands. We thank the Center for Information Technology of the University of Groningen (RUG) for their support and for providing access to the Peregrine high performance computing cluster, the Genomics Coordination Center (UMCG and RUG) for their support and for providing access to Calculon and Boxy high-performance computing clusters and the MOLGENIS team for data management and analysis support. Metagenomics library preparation and sequencing was done at Novogene. We also thank K. Mc Intyre for English and content editing and Tania Ballve Fernandez for illustration of Fig. 1a. Sequencing of the cohort was funded by a grant from CardioVasculair Onderzoek Nederland (CVON 2012-03) to M.H., J.F. and A.Z. R.G., H.J.M.H. and R.K.W. are supported by the collaborative TIMID project (LSHM18057-SGF) financed by the PPP allowance made available by Top Sector Life Sciences & Health to Samenwerkende Gezondheidsfondsen (SGF) to stimulate public–private partnerships and co-financed by health foundations that are part of the SGF. R.K.W. is supported by the Seerave Foundation and the Dutch Digestive Foundation (16-14). A.Z. is supported by European Research Council (ERC) Starting Grant 715772, Netherlands Organization for Scientific Research (NWO) VIDI grant 016.178.056, CVON grant 2018-27 and NWO Gravitation grant ExposomeNL 024.004.017. JF is supported by the Dutch Heart Foundation IN-CONTROL (CVON2018-27), the ERC Consolidator grant (grant agreement No. 101001678), NWO-VICI grant VI.C.202.022, and the Netherlands Organ-on-Chip Initiative, an NWO Gravitation project (024.003.001) funded by the Ministry of Education, Culture and Science of the government of The Netherlands. C.W. is further supported by an ERC advanced grant (ERC-671274) and an NWO Spinoza award (NWO SPI 92-266). L.C. is supported by a joint fellowship from the University Medical Center Groningen and China Scholarship Council (CSC201708320268) and a Foundation De Cock-Hadders grant (20:20-13). M.A.S. is supported by NWO VIDI grant 016 and EUCAN-connect, a project funded by European Commission H2020 grant 824989. Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Nature Limited.
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