Utilising single-cell sequencing in clinical nutraceutical research: Recent progress and perspectives

Xiaoqiang Wang , Yin S. Chan , David Sadava , Shiuan Chen

Clinical and Translational Discovery ›› 2025, Vol. 5 ›› Issue (1) : e70032

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Clinical and Translational Discovery ›› 2025, Vol. 5 ›› Issue (1) : e70032 DOI: 10.1002/ctd2.70032
RESEARCH ARTICLE

Utilising single-cell sequencing in clinical nutraceutical research: Recent progress and perspectives

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Abstract

Background: Single-cell sequencing technologies have revolutionised pharmaceutical research by providing in-depth insights into human biology at the single-cell level. These tools enable researchers to identify rare cell types and analyse cellular diversity within tissues, facilitating the discovery of new therapeutic targets and biomarkers. However, their application in nutraceutical research is still in its early stages.

Main Body: Unlike pharmaceuticals, which have well-defined chemical structures and mechanisms, nutraceuticals are food-based materials intended for specific medical purposes and often contain complex and diverse food chemicals. These molecules can work synergistically, producing multi-targeted effects in various tissues. Traditional bulk profiling methods for tissues and tumours do not adequately capture cellular heterogeneity or specific cellular responses to treatments. Therefore, advanced single-cell sequencing is crucial for dissecting tissues into distinct cell types, helping to clarify the underlying mechanisms at the cellular level. Many derivatives of functional foods have been marketed or assessed, demonstrating health benefits. However, mechanistic insights are lacking, with most current data derived from observational studies or traditional in vitro and in vivo models. Human clinical trials are needed to validate these nutraceutical effects and determine effective and safe dosages. Edible mushrooms have gained attention as nutraceuticals due to their medicinal properties. They have been observed to enhance immunity, reduce inflammation, and combat cancer. These effects have been attributed to their unique bioactive components and historical uses in traditional medicine. Epidemiological studies show that higher consumption of edible mushrooms is linked to a reduced risk of certain cancers.

Conclusion: In this review, we share important lessons learned in the design and execution of clinical trials focusing on white button mushrooms as anti-cancer nutraceuticals. We demonstrate the use of single-cell RNA sequencing (scRNA-seq) in nutraceutical research to capture the nuanced biological responses and health effects of dietary foods and their constituents.

Keywords

biomarkers / clinical trials / mechanism of actions / nutraceuticals / single-cell sequencing

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Xiaoqiang Wang, Yin S. Chan, David Sadava, Shiuan Chen. Utilising single-cell sequencing in clinical nutraceutical research: Recent progress and perspectives. Clinical and Translational Discovery, 2025, 5(1): e70032 DOI:10.1002/ctd2.70032

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References

[1]

Van de SandeB, LeeJS, Mutasa-GottgensE, et al. Applications of single-cell RNA sequencing in drug discovery and development. Nat Rev Drug Discov. 2023;22(6):496-520.

[2]

RamónY, CajalS, SeséM, CapdevilaC, et al. Clinical implications of intratumor heterogeneity: challenges and opportunities. J Mol Med. 2020;98(2):161-177.

[3]

JovicD, LiangX, ZengH, Lin L, XuF, LuoY. Single-cell RNA sequencing technologies and applications: a brief overview. Clin Transl Med. 2022;12(3):e694.

[4]

KarlssonM, ZhangC, MéarL, et al. A single-cell type transcriptomics map of human tissues. Sci Adv. 2021;7(31):eabh2169.

[5]

ZhaoJ, ShiY, CaoG. The application of single-cell RNA sequencing in the inflammatory tumor microenvironment. Biomolecules. 2023;13(2):344.

[6]

SunB, XunZ, ZhangN, Liu K, ChenX, ZhaoH. Single-cell RNA sequencing in cancer research: discovering novel biomarkers and therapeutic targets for immune checkpoint blockade. Cancer Cell Int. 2023;23(1):313.

[7]

YeB, JiH, ZhuM, et al. Single-cell sequencing reveals novel proliferative cell type: a key player in renal cell carcinoma prognosis and therapeutic response. Clin Exp Med. 2024;24(1):167.

[8]

WangX, ChengX, LiuH, MuX, ZhengH. Food nutrition and toxicology targeting on specific organs in the era of single-cell sequencing. Food Sci Human Wellness. 2024;13(1):75-89.

[9]

PanditaD, Pandita A. Omics technology for the promotion of nutraceuticals and functional foods. Front Physiol. 2022;13:817247.

[10]

StegA, Oczkowicz M, SmołuchaG. Omics as a tool to help determine the effectiveness of supplements. Nutrients. 2022;14(24):5305.

[11]

FergusonLR. Nutrigenomics approaches to functional foods. J Am Diet Assoc. 2009;109(3):452-458.

[12]

FlorisM, CanoA, PorruL, et al. Direct-to-Consumer nutrigenetics testing: an overview. Nutrients. 2020;12(2):566.

[13]

TangX, HuangY, LeiJ, LuoH, ZhuX. The single-cell sequencing: new developments and medical applications. Cell Biosci. 2019;9:53.

[14]

ZhuY, OuyangZ, DuH, et al. New opportunities and challenges of natural products research: when target identification meets single-cell multiomics. Acta Pharm Sin B. 2022;12(11):4011-4039.

[15]

ValverdeME, Hernández-Pérez T, Paredes-LópezO. Edible mushrooms: improving human health and promoting quality life. Int J Microbiol. 2015;2015:376387.

[16]

AssemieA, AbayaG. The effect of edible mushroom on health and their biochemistry. Int J Microbiol. 2022;2022:8744788.

[17]

HamzaA, Mylarapu A, KrishnaKV, KumarDS. An insight into the nutritional and medicinal value of edible mushrooms: a natural treasury for human health. J Biotechnol. 2024;381:86-99.

[18]

WuC, LeeS-L, TaylorC, et al. Scientific and regulatory approach to Botanical Drug Development: a U.S. FDA perspective. J Nat Prod. 2020;83:552-562.

[19]

SorkinBC, KuszakAJ, BlossG, et al. Improving natural product research translation: from source to clinical trial. FASEB J. 2019;34:41-65.

[20]

PuriV, NagpalM, SinghI, et al. A comprehensive review on nutraceuticals: therapy support and formulation challenges. Nutrients. 2022;14(21):4637.

[21]

EvansM, LewisED, AntonyJM, Crowley DC, GuthrieN, BlumbergJB. Breaking new frontiers: assessment and re-evaluation of clinical trial design for nutraceuticals. Front Nutr. 2022;9:958753.

[22]

WangX, HaD, YoshitakeR, Chen S. White button mushroom interrupts tissue AR-mediated TMPRSS2 expression and attenuates pro-inflammatory cytokines in C57BL/6 mice. NPJ Sci Food. 2021;5(1):20.

[23]

TwardowskiP, KanayaN, FrankelP, et al. A phase i trial of mushroom powder in patients with biochemically recurrent prostate cancer: roles of cytokines and myeloid-derived suppressor cells for agaricus bisporus-induced prostate-specific antigen responses. Cancer. 2015;121(17):2942-2950.

[24]

WangX, HaD, MoriH, Chen S. White button mushroom (Agaricus bisporus) disrupts androgen receptor signaling in human prostate cancer cells and patient-derived xenograft. J Nutr Biochem. 2021;89:108580.

[25]

DzubnarJ, YeeL, ChenS. White button mushroom and biomarkers of immune cell and inflammatory responses in obese postmenopausal women at high risk of breast cancer [abstract]. Proceedings of the 2023 San Antonio Breast Cancer Symposium, 5–9 Dec 2023, San Antonio, TX; 2023. Philadelphia (PA):AACR; Cancer Res 2024;84(9 Suppl):PO3-19-02.

[26]

FlemingTR, PowersJH. Biomarkers and surrogate endpoints in clinical trials. Stat Med. 2012;31(25):2973-2984.

[27]

SunY, QianJ. Botanical drug clinical trial: common issues and future options. Acta Pharm Sin B. 2021;11(1):300-303.

[28]

PalitS, HeuserC, de AlmeidaGP, TheisFJ, Zielinski CE. Meeting the challenges of high-dimensional single-cell data analysis in immunology. Front Immunol. 2019;10:1515.

[29]

WangX, ChanYS, WongK, et al. Mechanism-Driven and clinically focused development of botanical foods as multitarget anticancer medicine: collective perspectives and insights from preclinical studies, IND applications and early-phase clinical trials. Cancers. 2023;15(3):701.

[30]

FunkJL, Schneider C. Perspective on improving the relevance, rigor, and reproducibility of botanical clinical trials: lessons learned from turmeric trials. Front Nutr. 2021;8:782912.

[31]

LiZH, AiN, YuLX, QianZZ, ChengYY. A multiple biomarker assay for quality assessment of botanical drugs using a versatile microfluidic chip. Sci Rep. 2017;7(1):12243.

[32]

WuD, PaeM, RenZ, GuoZ, SmithD, Meydani SN. Dietary supplementation with white button mushroom enhances natural killer cell activity in C57BL/6 mice. J Nutr. 2007;137(6):1472-1477.

[33]

RenZ, GuoZ, MeydaniSN, Wu D. White button mushroom enhances maturation of bone marrow-derived dendritic cells and their antigen presenting function in mice. J Nutr. 2008;138(3):544-550.

[34]

WangX, MaS, TwardowskiP, et al. Reduction of myeloid-derived suppressor cells in prostate cancer murine models and patients following white button mushroom treatment. Clin Transl Med. 2024;14(10):e70048.

[35]

SatijaR, ShalekAK. Heterogeneity in immune responses: from populations to single cells. Trends Immunol. 2014;35(5):219-229.

[36]

FanJ, Slowikowski K, ZhangF. Single-cell transcriptomics in cancer: computational challenges and opportunities. Exp Mol Med. 2020;52(9):1452-1465.

[37]

ZhaoW, DovasA, SpinazziEF, et al. Deconvolution of cell type-specific drug responses in human tumor tissue with single-cell RNA-seq. Genome Med. 2021;13(1):82.

[38]

GebrayelP, NiccoC, Al KhodorS, et al. Microbiota medicine: towards clinical revolution. J Transl Med. 2022;20(1):111.

[39]

ChenX, PanS, LiF, XuX, XingH. Plant-derived bioactive compounds and potential health benefits: involvement of the gut microbiota and its metabolic activity. Biomolecules. 2022;12(12):1871.

[40]

YenS, Johnson JS. Metagenomics: a path to understanding the gut microbiome. Mamm Genome. 2021;32(4):282-296.

[41]

Lloréns-RicoV, Simcock JA, HuysGRB, RaesJ. Single-cell approaches in human microbiome research. Cell. 2022;185(15):2725-2738.

[42]

HaqueA, EngelJ, TeichmannSA, Lönnberg T. A practical guide to single-cell RNA-sequencing for biomedical research and clinical applications. Genome Med. 2017;9(1):75.

[43]

DenisenkoE, GuoBB, JonesM, et al. Systematic assessment of tissue dissociation and storage biases in single-cell and single-nucleus RNA-seq workflows. Genome Biol. 2020;21(1):130.

[44]

ParkJ, KimJ, LewyT, et al. Spatial omics technologies at multimodal and single cell/subcellular level. Genome Biol. 2022;23(1):256.

[45]

YoshitakeR, MoriH, HaD, et al. Molecular features of luminal breast cancer defined through spatial and single-cell transcriptomics. Clin Transl Med. 2024;14(1):e1548.

[46]

RaiSN, MishraD, SinghP, Vamanu E, SinghMP. Therapeutic applications of mushrooms and their biomolecules along with a glimpse of in silico approach in neurodegenerative diseases. Biomed Pharmacother. 2021;137:111377.

[47]

SpurgatMS, TangSJ. Single-cell RNA-sequencing: astrocyte and microglial heterogeneity in health and disease. Cells. 2022;11(13):2021.

[48]

MinochaT, BirlaH, ObaidAA, et al. Flavonoids as promising neuroprotectants and their therapeutic potential against Alzheimer’s disease. Oxid Med Cell Longev. 2022;2022:6038996.

[49]

RendeiroC, Spencer JP, VauzourD, ButlerLT, EllisJA, WilliamsCM. The impact of flavonoids on spatial memory in rodents: from behaviour to underlying hippocampal mechanisms. Genes Nutr. 2009;4(4):251-270.

[50]

LiJ, SunM, CuiX, LiC. Protective effects of flavonoids against Alzheimer’s disease: pathological hypothesis, potential targets, and structure–activity relationship. Int J Mol Sci. 2022;23(17):10020.

[51]

HeY, LuW, ZhouX, Mu J, ShenW. Unraveling Alzheimer’s disease: insights from single-cell sequencing and spatial transcriptomic. Front Neurol. 2024;15:1515981.

[52]

Boakye SerebourT, Cribbs AP, BaldwinMJ, et al. Overcoming barriers to single-cell RNA sequencing adoption in low-and middle-income countries. Eur J Hum Genet. 2024;32(10):1206-1213.

[53]

VandereykenK, SifrimA, ThienpontB, et al. Methods and applications for single-cell and spatial multi-omics. Nat Rev Genet. 2023;24:494-515.

[54]

WangX, FanD, YangY, Gimple RC, ZhouS. Integrative multi-omics approaches to explore immune cell functions: challenges and opportunities. iScience. 2023;26(4):106359.

[55]

ZhaoL, ZhangH, LiN, et al. Network pharmacology, a promising approach to reveal the pharmacology mechanism of Chinese medicine formula. J Ethnopharmacol. 2023;309:116306.

[56]

VeselkovK, Gonzalez G, AljifriS, et al. HyperFoods: machine intelligent mapping of cancer-beating molecules in foods. Sci Rep. 2019;9(1):9237.

[57]

GonzalezG, GongS, LaponogovI, Bronstein M, VeselkovK. Predicting anticancer hyperfoods with graph convolutional networks. Hum Genomics. 2021;15(1):33.

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2025 The Author(s). Clinical and Translational Discovery published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.

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