TY - JOUR
T1 - Genetic and gut microbiome determinants of SCFA circulating and fecal levels, postprandial responses and links to chronic and acute inflammation
AU - Nogal, Ana
AU - Asnicar, Francesco
AU - Vijay, Amrita
AU - Kouraki, Afroditi
AU - Visconti, Alessia
AU - Louca, Panayiotis
AU - Wong, Kari
AU - Baleanu, Andrei-Florin
AU - Giordano, Francesca
AU - Wolf, Jonathan
AU - Hadjigeorgiou, George
AU - Davies, Richard
AU - Michelotti, Gregory A
AU - Franks, Paul W.
AU - Berry, Sarah
AU - Falchi, Mario
AU - Ikram, Adeel
AU - Ollivere, Benjamin J.
AU - Zheng, Amy
AU - Nightingale, Jessica
AU - Massimo, Mangino
AU - Segata, Nicola
AU - Bulsiewicz, William J.
AU - Spector, Tim
AU - Valdes, Ana M.
AU - Menni, Cristina
N1 - Funding Information:
This research was funded by the Chronic Disease Research Foundation and in part by the Wellcome Trust [Grant number: 212904/Z/18/Z] and by Diabetes UK [19/0006053]. For the purpose of open access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. TwinsUK receives funding from the Wellcome Trust, the European Commission H2020 grants SYSCID (contract #733100); the National Institute for Health Research (NIHR) Clinical Research Facility and the Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London, the Chronic Disease Research foundation, the UKRI Medical Research Council (MRC)/British Heart Foundation Ancestry and Biological Informative Markers for Stratification of Hypertension (AIM-HY; MR/M016560/1), and Zoe Limited. This work was also supported by UKRI grant MR/W026813/1 to CM and AMV. MM is supported by the National Institute for Health Research (NIHR) Clinical Research Facility and the Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. AN, PL and CM are funded by the Chronic Disease Research Foundation. CM is also supported by the UKRI Medical Research Council (MRC)/British Heart Foundation Ancestry and Biological Informative Markers for Stratification of Hypertension (AIM-HY; MR/M016560/1). AMV is supported by the National Institute for Health Research Nottingham Biomedical Research Centre. The collection of samples from trauma patients was supported by the NIHR Research Nottingham Biomedical Research Centre and by NIHR grants NIHR132240 (OPERA) and 16/61/10 (ORiF) to BJO. The ZOE PREDICT-1 cohort is supported by Zoe Limited. We thank all the participants of TwinsUK, ZOE PREDICT-1 and the acute trauma case-control cohorts for contributing and supporting our research.
Publisher Copyright:
© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.
PY - 2023
Y1 - 2023
N2 - Short-chain fatty acids (SCFA) are involved in immune system and inflammatory responses. We comprehensively assessed the host genetic and gut microbial contribution to a panel of eight serum and stool SCFAs in two cohorts (TwinsUK, n = 2507; ZOE PREDICT-1, n = 328), examined their postprandial changes and explored their links with chronic and acute inflammatory responses in healthy individuals and trauma patients. We report low concordance between circulating and fecal SCFAs, significant postprandial changes in most circulating SCFAs, and a heritable genetic component (average h
2 : serum = 14%(SD = 14%); stool = 12%(SD = 6%)). Furthermore, we find that gut microbiome can accurately predict their fecal levels (AUC>0.71) while presenting weaker associations with serum. Finally, we report different correlation patterns with inflammatory markers depending on the type of inflammatory response (chronic or acute trauma). Our results illustrate the breadth of the physiological relevance of SCFAs on human inflammatory and metabolic responses highlighting the need for a deeper understanding of this important class of molecules.
AB - Short-chain fatty acids (SCFA) are involved in immune system and inflammatory responses. We comprehensively assessed the host genetic and gut microbial contribution to a panel of eight serum and stool SCFAs in two cohorts (TwinsUK, n = 2507; ZOE PREDICT-1, n = 328), examined their postprandial changes and explored their links with chronic and acute inflammatory responses in healthy individuals and trauma patients. We report low concordance between circulating and fecal SCFAs, significant postprandial changes in most circulating SCFAs, and a heritable genetic component (average h
2 : serum = 14%(SD = 14%); stool = 12%(SD = 6%)). Furthermore, we find that gut microbiome can accurately predict their fecal levels (AUC>0.71) while presenting weaker associations with serum. Finally, we report different correlation patterns with inflammatory markers depending on the type of inflammatory response (chronic or acute trauma). Our results illustrate the breadth of the physiological relevance of SCFAs on human inflammatory and metabolic responses highlighting the need for a deeper understanding of this important class of molecules.
KW - Short-chain fatty acids
KW - postprandial
KW - heritability
KW - gut microbiota
KW - inflammatory response
UR - http://www.scopus.com/inward/record.url?scp=85166069357&partnerID=8YFLogxK
U2 - ]10.1080/19490976.2023.2240050
DO - ]10.1080/19490976.2023.2240050
M3 - Article
SN - 1949-0976
VL - 15
JO - Gut Microbes
JF - Gut Microbes
IS - 1
M1 - 2240050
ER -
