Authors: Aurélie Cotillard 1Agnès Cartier-Meheust 1Nicole S Litwin 2 3Soline Chaumont 1Mathilde Saccareau 4Franck Lejzerowicz 2 3Julien Tap 1Hana Koutnikova 1Diana Gutierrez Lopez 2Daniel McDonald 3Se Jin Song 2Rob Knight 2 3 5 6Muriel Derrien 1Patrick Veiga 1

Background: Individual diet components and specific dietary regimens have been shown to impact the gut microbiome.

Objective: Here, we explored the contribution of long-term diet by searching for dietary patterns that would best associate with the gut microbiome in a population-based cohort.

Methods: Using a priori and a posteriori approaches, we constructed dietary patterns from a food frequency questionnaire completed by 1800 adults in the American Gut Project. Dietary patterns were defined as groups of participants or combinations of food variables (factors) driven by criteria ranging from individual nutrients to overall diet. We associated these patterns with 16S rRNA-based gut microbiome data for a subset of 744 participants.

Results: Compared to individual features (e.g., fiber and protein), or to factors representing reduced number of dietary features, five a posteriori dietary patterns based on food groups, were best associated with gut microbiome beta-diversity (P ≤ 0.0002). Two patterns followed Prudent-like diets from plant-based to flexitarian and exhibited the highest Healthy Eating Index 2010 (HEI-2010) scores. Two other patterns presented Western-like diets with a gradient in HEI-2010 scores. A fifth pattern consisted mostly of participants following an exclusion diet (e.g., low-carbohydrate). Notably, gut microbiome alpha-diversity was significantly lower in the most Western pattern compared to the flexitarian pattern (P ≤ 0.009), and the exclusion diet was associated with low relative abundance of Bifidobacterium (P ≤ 1.2 × 10-7), which was better explained by diet than health status.

Conclusions: We demonstrated that global-diet a posteriori patterns were more associated with gut microbiome variations than individual dietary features among adults in the United States. These results confirm that evaluating diet as a whole is important when studying the gut microbiome. It will also facilitate the design of more personalized dietary strategies in general populations.

Keywords: 16S rRNA gene sequencing; American Gut Project; Healthy Eating Index; alpha diversity; beta diversity; cohort study; dietary patterns; food frequency questionnaire; gut microbiome

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