Mengist, M. F. | Search bioRxiv

bioRxiv2025

Inhibition of pro-atherogenic trimethylamine production by human gut bacteria is not determined by varying chlorogenic acid content in highbush blueberries

Elevated blood levels of trimethylamine N-oxide (TMAO) are linked to increased risk of atherosclerosis. TMAO is produced when gut bacteria metabolize quaternary amines such as choline to trimethylamine (TMA), which is converted to TMAO in the liver. Chlorogenic acid (CGA), a phenolic abundant in blueberries, inhibits TMA production. Blueberries may be a TMA- (and TMAO)-lowering food. CGA content in blueberries varies significantly. It remains unclear whether variations in CGA levels influence the TMA-lowering activity of different cultivars. We investigated the impact of blueberry CGA content on inhibition of choline-d9 conversion to TMA-d9 in our upper gastrointestinal and in vitro human fecal model. Preliminary experiments indicated near-total inhibition of TMA-d9 production when whole blueberries were tested. Blueberry pulp and sugars recapitulated this complete inhibition, whereas blueberry skins and a fiber had more moderate inhibition. We proceeded with skins (to avoid interferences from sugar-rich pulp, which would not be present in the colon in vivo) from 20 highbush blueberry genotypes, chosen for extremes in CGA content. CGA in whole berries was 2.6-146 mg/100 g fresh weight, while CGA in skins was 13.6-975 mg/100 g fresh weight. No differences were observed in TMA-d9 production among the 4 highest and 4 lowest CGA genotypes in kinetic curves or area under the curve (AUC) values when skin digesta were fermented with choline-d9. However, significant differences were observed between all genotypes compared to blank digesta, with [~]19.4.% reduction in TMA-d9 AUCs, indicating that skins provides similar TMA-lowering benefits across genotypes. Levels of free CGA in fermenta of skin digesta were 0.05-0.3 M, >1000-fold lower than the minimum effective dose we observed for pure CGA in vitro, suggesting that blueberry CGA content is not a crucial factor for lowering TMA. Fiber also does not account for most of the inhibitory activity of blueberry skins. Studies are needed to confirm this in vitro study and understand how blueberries inhibit TMA and potentially TMAO production in vivo.

microbiology↗

bioRxiv2023

Blueberry and cranberry pangenomes as a resource for future genetic studies and breeding efforts

Domestication of cranberry and blueberry began in the United States in the early 1800s and 1900s, respectively, and in part owing to their flavors and health-promoting benefits are now cultivated and consumed worldwide. The industry continues to face a wide variety of production challenges (e.g. disease pressures) as well as a demand for higher-yielding cultivars with improved fruit quality characteristics. Unfortunately, molecular tools to help guide breeding efforts for these species have been relatively limited compared with those for other high-value crops. Here, we describe the construction and analysis of the first pangenome for both blueberry and cranberry. Our analysis of these pangenomes revealed both crops exhibit great genetic diversity, including the presence-absence variation of 48.4% genes in highbush blueberry and 47.0% genes in cranberry. Auxiliary genes, those not shared by all cultivars, are significantly enriched with molecular functions associated with disease resistance and the biosynthesis of specialized metabolites, including compounds previously associated with improving fruit quality traits. The discovery of thousands of genes, not present in the previous reference genomes for blueberry and cranberry, will serve as the basis of future research and as potential targets for future breeding efforts. The pangenome, as a multiple-sequence alignment, as well as individual annotated genomes, are publicly available for analysis on the Genome Database for Vaccinium - a curated and integrated web-based relational database. Lastly, the core-gene predictions from the pangenomes will serve useful to develop a community genotyping platform to guide future molecular breeding efforts across the family.

genomics↗