4.7 Article

Interaction of n-3 polyunsaturated fatty acids with host CD36 genetic variant for gut microbiome and blood lipids in human cohorts

Journal

CLINICAL NUTRITION
Volume 41, Issue 8, Pages 1724-1734

Publisher

CHURCHILL LIVINGSTONE
DOI: 10.1016/j.clnu.2022.05.021

Keywords

Fatty acids; Gene-diet interaction; Blood lipids; Gut microbiome; Host metabolites

Funding

  1. National Natural Science Foundation of China [81903316, 82073529, 81773416, 81970684, 82103826]
  2. Strategic Priority Research Program of Chinese Academy of Sciences [XDB38010300]
  3. Zhejiang Ten-thousand Talents Program [2019R52039]
  4. Shanghai Municipal Science and Technology Major Project [2017SHZDZX01]
  5. China Postdoctoral Science Foundation [2020M681945]
  6. Zhejiang Provincial Natural Science Foundation of China [LQ21H260002]
  7. Zhejiang Postdoctoral Science Foundation [ZJ2020076]
  8. Key Research and Development Program for Science and Technology Projects of Zhejiang Province [2017C02003]
  9. 5010 Program for Clinical Researches of the Sun Yat-sen University [2007032]

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This study found that high n-3 PUFAs were associated with improved blood lipids and gut microbial features only among rs1527483-GG carriers.
Background & aims: Previous studies suggest an interaction of CD36 genetic variant rs1527483 with n-3 polyunsaturated fatty acids (PUFAs) to modulate blood lipids. However, successful replication is lacking and the role of gut microbiome remains unclear. Here, we aimed to replicate these gene-diet interactions on blood lipids and investigate their possible associations with gut microbiome. Methods: We evaluated the n-3 PUFA-rs1527483 interaction on blood lipids in two population-based cohorts (n 1/4 4,786). We profiled fecal microbiome and short-chain fatty acids among 1,368 participants. The associations between n-3 PUFAs and bacterial alpha-diversity, taxonomies and short-chain fatty acids by rs1527483 genotypes were analyzed using regression models. Results: CD36 rs1527483-GG carriers responded better to high n-3 PUFA exposure; higher blood HDL-C (beta (95% CI): 0.05 (0.01, 0.08) mmol/L) and lower TG (log-transformed, beta (95% CI):-0.08 (-0.14,-0.02)) were observed among participants whose n-3 PUFA exposure ranked in the top quartile comparing with those in the bottom quartile. We identified docosahexaenoic acid (DHA) as the driven individual n-3 PUFA biomarker, which showed interaction with rs1527483. Among the rs1527483-GG carriers, but not other genotype groups, DHA exposure was positively associated with bacterial Faith's phylogenetic diversity, Observed OTUs, Shannon's diversity index, Dorea, Coriobacteriales Incertae Sedis spp, and fecal propionic acid levels. Another independent longitudinal cohort validated the DHArs1527483 interaction on gut microbiome. The identified microbial features were correlated with blood lipids, and the host biosynthesis and metabolism pathways of bile acids and aromatic amino acids. Conclusions: The present study found that higher n-3 PUFAs were associated with improved blood lipids and gut microbial features only among rs1527483-GG carriers. These findings highlight a potential role of gut microbiome to link the CD36 genetic variant, n-3 PUFAs and blood lipids, revealing a new research direction to interpret the gene-diet interaction for cardiometabolic health. (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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