Effects of Lean Pork on Microbiota and Microbial-Metabolite Trimethylamine-N-Oxide: A Randomized Controlled Non-Inferiority Feeding Trial Based on the Dietary Guidelines for Americans

Abstract

Scope: Trimethylamine-N-oxide (TMAO) is a microbiota-dependent and primarily animal-protein-derived proatherogenic metabolite. The ecological impact of pork-the most popular animal protein worldwide-on the human microbiome, and in the physiological context of TMAO and other biogenic amines, remains unknown. Poultry being the recommended heart-healthier animal protein, we investigated-if pork intake results in inferior-to-chicken TMAO-response while consuming a diet based on the Dietary Guidelines for Americans (DGA).

Methods and results: In a randomized, controlled, all-food-provided, crossover, feeding trial, healthy adults consumed 156 g day^-1 of lean-pork or chicken (active-control) as primary proteins. Mixed-effect modeling shows pork as noninferior to chicken for circulating TMAO response and microbiota-generated essential TMAO-precursor-trimethylamine (97.5% CI, n = 36/protein). Markers of lipid metabolism, inflammation and oxidative stress, serum levels of betaine, choline, L-carnitine, composition and functional-capability of the microbiota, and association of baseline TMAO-levels with TMAO-response (both, r > 0.6, p = 0.0001) are nondistinguishable between the protein groups. TMAO reduction and similar shifts in microbiota and biogenic-amine signatures postdiet in both groups indicate a background DGA-effect.

Conclusion: Unlike extrapolating negative results, this study presents noninferiority-testing based evidence. Consuming pork as a predominant protein within an omnivorous DGA-diet does not exacerbate TMAO-response. Results highlight the importance of understanding protein-TMAO interactions within dietary patterns.

Keywords: controlled-feeding study; dietary guidelines for Americans/DGA; lean pork; microbiota; non-inferiority/NI randomized controlled trial; trimethylamine-N-oxide/TMAO.