Critical Evaluation of Gene Expression Changes in Human Tissues in Response to Supplementation with Dietary Bioactive Compounds: Moving Towards Better-Quality Studies

Abstract

Pre-clinical cell and animal nutrigenomic studies have long suggested the modulation of the transcription of multiple gene targets in cells and tissues as a potential molecular mechanism of action underlying the beneficial effects attributed to plant-derived bioactive compounds. To try to demonstrate these molecular effects in humans, a considerable number of clinical trials have now explored the changes in the expression levels of selected genes in various human cell and tissue samples following intervention with different dietary sources of bioactive compounds. In this review, we have compiled a total of 75 human studies exploring gene expression changes using quantitative reverse transcription PCR (RT-qPCR). We have critically appraised the study design and methodology used as well as the gene expression results reported. We herein pinpoint some of the main drawbacks and gaps in the experimental strategies applied, as well as the high interindividual variability of the results and the limited evidence supporting some of the investigated genes as potential responsive targets. We reinforce the need to apply normalized procedures and follow well-established methodological guidelines in future studies in order to achieve improved and reliable results that would allow for more relevant and biologically meaningful results.

Amazonian Eryngium foetidum leaves exhibited very high contents of bioactive compounds and high singlet oxygen quenching capacity

“…As examples, these compounds were reported to inhibit the induction of several proinflammatory cytokines and the impairment of endogenous antioxidant enzymatic systems during inflammation, [10] and they are frequently associated with changes in the expression of genes implicated in cancer development, transcription, apoptosis, xenobiotic metabolism, inflammation, redox process, among others. [11] Furthermore, one of the main biological actions of these compounds is related to their antioxidant capacity to scavenge reactive species, such as reactive oxygen (ROS) and nitrogen (RNS) species. ROS and RNS exert normal physiological functions in the human organism; however, the overproduction of these species can damage cellular components, such as proteins, lipids and DNA, inducing the increased development of chronic degenerative diseases and premature aging.…”

An Exploratory Search for Potential Molecular Targets Responsive to the Probiotic Lactobacillus salivarius PS2 in Women With Mastitis: Gene Expression Profiling vs. Interindividual Variability

“…Along these lines, gene expression has been reported to be gene- and tissue-specific and enhanced in disease-associated genes as well as by the protocols (Nú-ez-Sánchez et al, 2017 ). In order to improve the selection and evaluation of responsive gene targets, the methodological variability must be controlled by means of improving sample attaining, description, processing and analyses protocols (Pokimica and García-Conesa, 2018 ). On the other hand the factors inherent to humans and causing interindividual variability are many (sex, age, health status, genetic make-up, microbiota) and we are only beginning to understand them (Manach et al, 2017 ).…”

Phytochemicals as Regulators of Genes Involved in Synucleinopathies

“…A growing number of studies reveal that the effect of phytochemicals from medicinal plants are displayed via epigenetic mechanisms ( Figure 2 ) by DNA methylation, histone modifications, microRNAs or LncRNAs [ 73 ].…”