High throughput platform development and powerful bioinformatics’ tools in combination have contributed to our comprehension of the role of nutraceuticals, probiotics and other bioactive ingredients in human health. They have helped us study the biological and the cellular responses induced by these supplements, allowing us to validate and understand their health promoting capabilities. Current trend in the omics approach is using multiple omics platforms in collaboration, to achieve a comprehensive understanding of the nutraceuticals and probiotics functionality in human health. Different omics platforms help in deepening our knowledge of interaction of nutraceuticals, bioactives and probiotics, with the host and studying their mechanism of actions, safety concerns, efficacy and characterization including development of new health ingredients from traditional medicines (1). Plant-derived bioactive molecules, phytonutrients, consisting of flavonoids and phenolic compounds have an important function in human diet and nutrition. Genomics, transcriptomics, proteomics and metabolomics are main omics analyses that can be used for functional foods and nutraceuticals (Figure 1). Natural phytochemicals may affect signaling pathways and genome expression which can be studied using genomics (nutrigenomics) and transcriptomics. Functional foods and nutraceuticals like carotenoids, polyamines, folates, phenolics, flavonoids and non-flavonoid condensed tannins have been shown to modulate various cellular processes (2,3).

The human and animal gastrointestinal tract is inhabited by countless microorganisms. The total number of genes of these microbes are estimated to be almost 150 times the number of human genes. These microbial genes have key roles in physiological functions and health of the host. Genome mining has allowed us to determine properties such as acid tolerance, antimicrobial peptides production in possible probiotic strains, metagenomics moreover contributes to understanding the probiotic-microbiota interaction. Transcriptomic, proteomic, and metabolomic platforms have supported the profiling of host–microbe crosstalk and have contextualized the holistic effects induced by the supplementation.

Nutrigenomics analyzes the interaction of nutrients with human genomic sequences and studies its influence on host genomic expression and transcription (4,5). Multiple omics platforms are now a necessity to gain understanding of the mechanism of action, as well as the impact on metabolic pathways and influence on homeostasis by nutraceuticals and probiotics in humans. Nutrigenomics is built on understanding the functional sensitivity of genes to nutrients which is evident from the metabolic complications that may be caused in infancy to later years, due to nutritional deficiencies in mothers. For the purpose of this article the word nutraceuticals will be used to cover all dietary ingredients and supplements used for promoting human health.

Genomics may involve studying structural genomics and functional genomics. Structural genomics determines the 3-D structures of proteins encoded by a given genome and includes a high-throughput method for structure determination through a combination of experimental and modeling approaches. A major part of genomics is sequencing the genomes of various organisms studying their genetic expression under various conditions. Functional genomics on the other hand attempts to describe gene and protein functions and their interactions.

In microbiology, genomics has allowed us to sequence diverse strains of multiple species, elucidating the pangenome for protein coding. Metagenomics on the other hand has allowed analyses of microbes, in particular the non-cultivable bacteria at stain levels (6). Genomic analyses have been used to determine the mechanisms of host-microbe interactions, including effects on cell signaling pathways, bile secretion, proteasome, cAMP signaling, thyroid hormone synthesis, and dopaminergic synapse pathways. For example, a recent study in 2020 used a genome-based approach to show presence of genes for lactic acid production, stress tolerance and antimicrobial peptides (7).

The DNA sequencing technology started from DNA microarrays to first generation Sanger sequencing, then came the second generation with massive parallel sequencing capabilities more commonly known as next generation sequencing with platforms such as 454 Genome sequencers (Roche Life Science, USA) and Illumina Genome Analyzer (Illumina, USA), and then the current third generation with long reads sequencing which has allowed sequencing whole genome so deep that mutational changes can be characterized enabled by Pacific Biosciences and Oxford Nanopore technologies (8).

Metagenomics and metatranscriptomics in conjunction have contributed to the development of an improved, new generation of probiotics. With these techniques we have a better understanding of the microbiome, and they can be used to generate valid hypotheses to determine the mechanism of dysbiosis progression in human body and its consequences (9). A large-scale genome wide analyses among lactic acid bacteria illustrated their diversity, prevalence and relationship to each other, and identified the link between gut and food microbiome (10). Metagenomics has been widely applied in the research of obesity, providing evidence for the important role of intestinal microbiota for obesity. There was a difference in relative abundance when the distal gut microbiota was compared for obese versus lean individuals, with increase in relative abundance of Bacteroidetes was observed when obese individuals lose weight (11). Metagenomics studies have also demonstrated an imbalanced microbiota composition in various diseases, for example Crohn's disease, necrotizing enterocolitis, polyposis or colorectal cancer, and type 2 diabetes (11).

The concept of transcriptomics is based on the central dogma theory where the genetic information flows from DNA to DNA (replication), from DNA to RNA (called transcription), and from RNA to protein (called translation). In this sequence the transcription results in the formation of a complete set of RNA consisting of ribosomal RNA, tRNA, mRNA and other non-coding RNAs. However, only mRNA carries the identities of individual genes and acts as bridges between genotypic information to the phenotypic expression of an organism. Transcriptomics includes the whole transcripts expressed from the genome, thus making it an ideal platform for studying the expression of various genes (12). Genetic expression measurements of genes in different tissues under various conditions at multiple time points provides information about gene regulation and reveals details of biologicals functions in an organism. It also provides information on previously unknown genes, hence transcriptomics analysis in its entirety has enabled us to understand trends in disease progression or health benefits downstream of a bioactive compound. Bioactive components from foods and dietary supplements can change gene expression by affecting the cellular pathways and metabolism, cell proliferation and differentiation and finally cell death and any imbalance in these processes can lead to development of diseases such as diabetes or cancer. Thus, the influence of nutraceuticals and other bioactive components on genetic expression at genome level is an important part of nutrigenomics investigations. Transcriptomic analysis has been employed in clinical trials to get an understanding of the effects of dietary interventions such as investigations for nutritional deficiency, intermittent fasting, or certain food components. Some of the most common pathways studied using transcriptomics in health promoting dietary interventions are glucose and insulin signaling, inflammation, oxidative phosphorylation, immune responses, and circadian rhythm (13). Transcriptomics was applied to study the internal response of cells to physical disturbances. It can also be applied to study the host-microbe interaction in understanding the effect of probiotics on host immune modulation for e.g., the effect of Bifidobacterium breve UCC2003 strain on strengthening the intestinal barrier by having an effect on the intestinal epithelial cells was demonstrated using transcriptomics. The strain influenced the epithelial cells by regulating gene expression and influencing metabolic pathways (14).

Before advancement in the next generation sequencing technologies, RNA microarrays were used. Some of the nutraceuticals and bioactives studied using microarray techniques for transcriptomics have been green tea catechins, vitamins, polyunsaturated fat, isoflavones, quercetins, anthocyanins, and arginine (1). Once RNA sequencing became available it was used to detect the abundance of RNA transcript in high throughput manner. Additionally, several other RNA sequencing platforms have also developed that involve tag based methods i.e. using one fragment to represent a transcript such as digital gene expression sequencing and 3’ end sequencing. Currently the transcriptomics technology is chip based which includes cDNA microarray and oligonucleotide chips, serial analysis of gene expression, and massively parallel signature sequencing and there are several other variations in the techniques which are beyond the scope of this article (8).

Similar to metagenomics, metatranscriptomics has been employed to determine the microbial composition and diversity from many ecological niches for e.g. researchers employed metatranscriptomics to study the complex interaction of the oral microbiome in biofilm assembly (15). Metatranscriptome analysis normally sequences the entire transcriptome from the microbial community and unravels the complex interactions between probiotics, the microbiome, and the host. It can give a clear picture of specific targets and precision application of probiotics, especially when coupled with other omics techniques such as proteomics and metabolomics (16).