Acupuncture and Herbal Medicine
|
2026, 6(3): 387-411
• Hundreds of Herbs •
Efficacy and toxicity in Gardeniae Fructus application: dual role effects mediated by gut microbiota–derived biotransformation
Full
Zixin Zhao
1, 2, Shilin Gong
1, 2, Chunyue Liu
1, 2, Jun Wen
1, 2, *, Tingting Zhou
1, 2, *
Affiliations
- 1School of Pharmacy, Naval Medical University, Shanghai 200433, China
- 2Shanghai Key Laboratory for Pharmaceutical Metabolite Research, School of Pharmacy, Naval Medical University, Shanghai 200433, China
About Author:
Zixin Zhao and Shilin Gong contributed equally to this work.
Published: 2026-09-25
doi: 10.1097/HM9.0000000000000211
Outline
Gardeniae Fructus (GF) is a well-known traditional Chinese medicine widely used in clinical prescriptions for its antidepressant, hepatoprotective, and other therapeutic effects. It contains multiple bioactive compounds, including iridoid glycosides, crocins, flavonoids, and organic acids. However, prolonged use or excessive doses of GF may lead to chronic or acute hepatotoxicity. This double-edged pharmacological profile has become a major obstacle to its clinical application. Accumulating evidence indicates that the gut microbiota plays a non-negligible role in the metabolism of traditional Chinese medicines. Notably, the dual effects of GF, both therapeutic and toxic, are closely associated with the microbial biotransformation of its active components, positioning the gut microbiota as a critical determinant of GF's efficacy and safety. Microbial enzymes may enhance the bioavailability and bioactivities of GF-derived ingredients, as well as generate novel metabolites with potential pharmacological activities. Concurrently, GF-induced alterations in bacterial composition may lead to changes in metabolic output, which further influence host physiological responses, thereby modulating the overall effects of GF. In this case, it is essential to incorporate gut microbiota–mediated bioactivities into the comprehensive evaluation of GF pharmacology. This review provides a comprehensive summary of the main bioactive compounds of GF and their biotransformation by the gut microbiota, and examines the dual effects of GF in the presence or absence of gut microbiota influences. Moreover, we discuss the potential of intestinal bacterial modulation as a strategy for balancing the efficacy and safety of GF. This review offers a thorough synthesis of the dual pharmacological actions of GF, while placing particular emphasis on the gut microbiota as a critical mediator of its divergent effects. We also offer new perspectives on the clinical potential of gut microbiota–targeted interventions to balance the dual effects of GF. The bidirectional crosstalk between gut microbiota and GF significantly influences the efficacy and toxicity of GF-derived compounds. Ecological management strategies may benefit the personalized treatment paradigm of GF, by accounting for interindividual variability in the gut microbiota.
Efficacy and toxicity
/
Gardeniae Fructus
/
Genipin
/
Gut microbiota
/
Gut-X axis
/
Microbial biotransformation
Zixin Zhao, Shilin Gong, Chunyue Liu, Jun Wen, Tingting Zhou.
Efficacy and toxicity in Gardeniae Fructus application: dual role effects mediated by gut microbiota–derived biotransformation[J].
Acupuncture and Herbal Medicine,
2026
, 6
(3)
: 387
-411
.
DOI: 10.1097/HM9.0000000000000211
- Funds for International Cooperation and Exchange of the National Natural Science Foundation of China(82461160264)
- National Natural Science Foundation of China(82474056; 82304687)
- Noncommunicable Chronic Diseases-National Science and Technology Major Project, China(2023ZD0502605)
- Shanghai Municipal Health Commission, China(2022XD037)
- Shanghai Magnolia Talent Plan Pujiang Project, China(23PJD113)
[1]
Yang W, Zhang W, Huang X, et al. Gut microbiota, a potential mediated target for reducing geniposide hepatotoxicity by interacting with isoflavones.
Engineering 2025;47:222–235.
[2]
Chen J, Tang W, Li C, et al. Multi-omics analysis reveals the molecular basis of flavonoid accumulation in fructus of Gardenia (Gardenia jasminoides Ellis).
BMC Genomics 2023;24(1):588.
[3]
Chen L, Li M, Yang Z, et al. Gardenia jasminoides Ellis: ethnopharmacology, phytochemistry, and pharmacological and industrial applications of an important traditional Chinese medicine.
J Ethnopharmacol 2020;257:112829.
[4]
He J, Zhao Z, Ye Y, et al. Microbiota basis of antidepressant effects of Zhi-zi-chi Decoction: Lactobacillus rhamnosus and gut microbiota metabolism.
Chin Herb Med 2025;17(4):798–807.
[5]
Tang S, Yan G, Kong L, et al. Research progress on the hepatoprotective effect, pharmacokinetic properties, and hepatotoxicity of geniposide.
Acupunct Herb Med 2025;5(2):136–146.
[6]
Wang X, Zhang Z, Wang J, et al. Preparation technologies, structural characteristics, pharmacological activities and applications of Gardenia jasminoides Ellis polysaccharides: a review.
Int J Biol Macromol 2025;319(Pt 3):145600.
[7]
Zheng L, Gong S, Wang X, et al. Preparation and characterization of pectin polysaccharides-containing Gardenia extract with dual functionality in food gel formation and coloring for 3D printing application.
Int J Biol Macromol 2026;344(Pt 1):150528.
[8]
Wang X, Tian T, Li N, et al. Characterization and gelling properties of pectin extracted from Gardenia fruit.
Food Hydrocoll 2025;163:111055.
[9]
Liang L, Liu J, Luo J, et al. Non-targeted metabolomic and chemometric analysis of Gardeniae Fructus (Zhizi): linking processing to chemical and bioactive changes.
J Ethnopharmacol 2026;355(Pt A):120606.
[10]
Han Y, Wen J, Zhou T, et al. Chemical fingerprinting of Gardenia jasminoides Ellis by HPLC-DAD-ESI-MS combined with chemometrics methods.
Food Chem 2015;188:648–657.
[11]
Wang L, Chen S, Liu S, et al. A comprehensive review of ethnopharmacology, chemical constituents, pharmacological effects, pharmacokinetics, toxicology, and quality control of Gardeniae fructus.
J Ethnopharmacol 2024;320:117397.
[12]
Gong X, Li X, Bo A, et al. The interactions between gut microbiota and bioactive ingredients of traditional Chinese medicines: a review.
Pharmacol Res Mod Chin Med 2025;16:100662.
[13]
Koeth RA, Wang Z, Levison BS, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis.
Nat Med 2013;19(5):576–585.
[14]
Lynch SV, Pedersen O. The human intestinal microbiome in health and disease.
N Engl J Med 2016;375(24):2369–2379.
[15]
Tiwari M, Suruchi, Gupta AK, Pal D, Jain SK. Phytochemical constituents, therapeutic potential and toxicity of Gardenia jasminoides Ellis: an in-depth review.
Pharmacol Res 2025;16:100662.
[16]
Jin MJ, Kim IS, Kim DH, et al. Effects of intestinal microbiota on the bioavailability of geniposide in rats.
J Agric Food Chem 2014;62(40):9632–9636.
[17]
Gao FY, Chen XF, Cui LX, et al. Gut microbiota mediates the pharmacokinetics of Zhi-zi-chi decoction for the personalized treatment of depression.
J Ethnopharmacol 2023;302(Pt B):115934.
[18]
Zhang Y, Fang YC, Cui LX, et al. Zhi-Zi-Chi decoction reverses depressive behaviors in CUMS rats by reducing oxidative stress injury
via regulating GSH/GSSG pathway.
Front Pharmacol 2022;13:887890.
[19]
Zhang Z-W, Wang W-P, Hu J-C, et al. Berberine protects cerebral vessels and alleviates diabetic encephalopathy by inhibiting the production of δ-Valerobetaine in the gut microbiota.
Engineering 2025;49:290–303.
[20]
Zhou YX, Zhang RQ, Rahman K, et al. Diverse pharmacological activities and potential medicinal benefits of geniposide.
Evid Based Complement Alternat Med 2019;2019:4925682.
[21]
Luo Y, Gao F, Chang R, et al. Metabolomics based comprehensive investigation of Gardeniae Fructus induced hepatotoxicity.
Food Chem Toxicol 2021;153:112250.
[22]
Li Y, Pan H, Li X, et al. Role of intestinal microbiota-mediated genipin dialdehyde intermediate formation in geniposide-induced hepatotoxicity in rats.
Toxicol Appl Pharmacol 2019;377:114624.
[23]
Xu H, Huang X, Zhang Y, et al. Genipin induces liver injury by disrupting the CPS1-regulated urea cycle and redox homeostasis.
J Pharm Anal 2026:101647.
[24]
Guo Y, Cheng Y, Zheng B, et al. Structural characterization and immunomodulatory activity of a novel pectin polysaccharide extracted from Gardenia jasminoides fruit.
Carbohydr Polym 2025;369:124337.
[25]
Tian J, Qin S, Han J, et al. A review of the ethnopharmacology, phytochemistry, pharmacology and toxicology of Fructus Gardeniae (Zhi-zi).
J Ethnopharmacol 2022;289:114984.
[26]
Jin C, Zongo AW, Du H, et al. Gardenia (Gardenia jasminoides Ellis) fruit: a critical review of its functional nutrients, processing methods, health-promoting effects, comprehensive application and future tendencies.
Crit Rev Food Sci Nutr 2025;65(1):165–192.
[27]
Chang R, Liu J, Luo Y, et al. Isoflavones’ effects on pharmacokinetic profiles of main iridoids from Gardeniae fructus in rats.
J Pharm Anal 2020;10(6):571–580.
[28]
Chyau CC, Chiu CY, Hsieh HL, et al. High-purity preparation of enzyme transformed trans-crocetin reclaimed from Gardenia fruit waste.
Plants (Basel) 2022;11(3):281.
[29]
Jin C, Wang L, Liu X, et al. Health oil preparation from gardenia seeds by aqueous enzymatic extraction combined with puffing pre-treatment and its properties analysis.
Food Sci Biotechnol 2023;32(14):2043–2055.
[30]
Lautenschlager M, Sendker J, Huwel S, et al. Intestinal formation of trans-crocetin from saffron extract (Crocus sativus L.) and in vitro permeation through intestinal and blood brain barrier.
Phytomedicine 2015;22(1):36–44.
[31]
Tiribuzi R, Crispoltoni L, Chiurchiu V, et al. Trans-crocetin improves amyloid-beta degradation in monocytes from Alzheimer's disease patients.
J Neurol Sci 2017;372:408–412.
[32]
Yu R, Li Y, Si D, et al. Identification, quantitative and bioactivity analyses of aroma and alcohol-soluble components in flowers of Gardenia jasminoides and its variety during different drying processes.
Food Chem 2023;420:135846.
[33]
Ai Z, Xiao Z, Liu M, et al. Evaluation of innovative drying technologies in Gardenia jasminoides Ellis drying considering product quality and drying efficiency.
Food Chem X 2024;24:102052.
[34]
Lin P, Chen L, Huang X, et al. Structural characteristics of polysaccharide GP2a in Gardenia jasminoides and its immunomodulatory effect on macrophages.
Int J Mol Sci 2022;23(19):11279.
[35]
Fang S, Wang T, Li Y, et al. Gardenia jasminoides Ellis polysaccharide ameliorates cholestatic liver injury by alleviating gut microbiota dysbiosis and inhibiting the TLR4/NF-kappaB signaling pathway.
Int J Biol Macromol 2022;205:23–36.
[36]
Ma X, Zhou W, Nie Y, et al. A novel branched galacturonan from Gardenia jasminoides alleviates liver fibrosis linked to TLR4/NF-kappaB signaling.
Int J Biol Macromol 2023;245:125540.
[37]
Shao J, Li T, Zeng S, et al. The structures of two acidic polysaccharides from Gardenia jasminoides and their potential immunomodulatory activities.
Int J Biol Macromol 2023;248:125895.
[38]
Zou S, Sun C, Li F, et al. Effect of gardenia pomace supplementation on growth performance, blood metabolites, immune and antioxidant indices, and meat quality in Xiangcun pigs.
Animals (Basel) 2022;12(17):2280.
[39]
Zhang A, Wang J, Hu Y, et al. Polysaccharides play an anti-fibrotic role by regulating intestinal flora: a review of research progress.
Int J Biol Macromol 2024;271(Pt 2):131982.
[40]
Sun X, Zheng Y, Tian Y, et al. Astragalus polysaccharide alleviates alcoholic-induced hepatic fibrosis by inhibiting polymerase I and transcript release factor and the TLR4/JNK/NF-kappaB/MyD88 pathway.
J Ethnopharmacol 2023;314:116662.
[41]
Zhang S, Waterhouse GIN, Cui T, et al. Pectin fractions extracted sequentially from Cerasus humilis: their compositions, structures, functional properties and antioxidant activities.
Food Sci Hum Wellness 2023;12(2):564–574.
[42]
Ao L, Li Y, Zheng L, et al. Self-assembling gardenia pectin gel for cholestatic liver injury: dual mechanisms of hepatoprotection
via PPARalpha activation and gut microbial modulation.
Carbohydr Polym 2026;384:125332.
[43]
Akao T, Kobashi K, Aburada M. Enzymic studies on the animal and intestinal bacterial metabolism of geniposide.
Biol Pharm Bull 1994;17(12):1573–1576.
[44]
Zhou J, Zhang Y, Li N, et al. A systematic metabolic pathway identification of common gardenia fruit (Gardeniae Fructus) in mouse bile, plasma, urine and feces by HPLC-QTOF-MS/MS.
J Chromatogr B Analyt Technol Biomed Life Sci 2020;1145:122100.
[45]
Kim YS, Lee CJ, Ma JY. Enhancement of active compound, genipin, from Gardeniae Fructus using immobilized glycosyl hydrolase family 3 beta-glucosidase from Lactobacillus antri.
AMB Express 2017;7(1):64.
[46]
Jiang P, Ma Y, Gao Y, et al. Comprehensive evaluation of the metabolism of Genipin-1-beta-d-gentiobioside in vitro and in vivo by using HPLC-Q-TOF.
J Agric Food Chem 2016;64(27):5490–5498.
[47]
Kawata Y, Hattori M, Akao T, et al. Formation of nitrogencontaining metabolites from geniposide and gardenoside by human intestinal bacteria.
Planta Med 1991;57(6):536–542.
[48]
Xu XX, Li XJ, Pan KW, et al. Microbial transformation of geniposide in Gardeniae Fructus under the fermentation with Aspergillus niger DQWM-G11.
Nat Prod Res 2025;39(18):5411–5417.
[49]
Yim JS, Kim YS, Moon SK, et al. Metabolic activities of ginsenoside Rb1, baicalin, glycyrrhizin and geniposide to their bioactive compounds by human intestinal microflora.
Biol Pharm Bull 2004;27(10):1580–1583.
[50]
Kim YS, Kim JJ, Cho KH, et al. Biotransformation of ginsenoside Rb1, crocin, amygdalin, geniposide, puerarin, ginsenoside Re, hesperidin, poncirin, glycyrrhizin, and baicalin by human fecal microflora and its relation to cytotoxicity against tumor cells.
J Microbiol Biotechnol 2008;18(6):1109–1114.
[51]
Garcia CJ, Beltran D, Frutos-Lison MD, et al. New findings in the metabolism of the saffron apocarotenoids, crocins and crocetin, by the human gut microbiota.
Food Funct 2024;15(18):9315–9329.
[52]
Zhang Y, Geng J, Hong Y, et al. Orally administered crocin protects against cerebral Ischemia/reperfusion injury through the metabolic transformation of Crocetin by gut microbiota.
Front Pharmacol 2019;10:440.
[53]
Xiao F, Song Y, Wang G, et al. Intestinal metabolism of crocin and a pharmacokinetics and pharmacodynamics study in the chronic social defeat stress mouse model.
Pharmaceuticals (Basel) 2024;17(7):843.
[54]
Naranjo Pinta M, Montoliu I, Aura AM, et al. In vitro gut metabolism of [U-(13) C]-quinic acid, the other hydrolysis product of chlorogenic acid.
Mol Nutr Food Res 2018;62(22):e1800396.
[55]
Hu LL, Hu Y, Song H, et al. In vitro research on metabolism of chlorogenic acid in liver microsomes and intestinal flora.
J Food Saf Qual 2021;12:9.
[56]
Gonthier MP, Verny MA, Besson C, et al. Chlorogenic acid bioavailability largely depends on its metabolism by the gut microflora in rats.
J Nutr 2003;133(6):1853–1859.
[57]
Tomas-Barberan F, Garcia-Villalba R, Quartieri A, et al. In vitro transformation of chlorogenic acid by human gut microbiota.
Mol Nutr Food Res 2014;58(5):1122–1131.
[58]
Gonthier MP, Remesy C, Scalbert A, et al. Microbial metabolism of caffeic acid and its esters chlorogenic and caftaric acids by human faecal microbiota in vitro.
Biomed Pharmacother 2006;60(9):536–540.
[59]
Braune A, Blaut M. Bacterial species involved in the conversion of dietary flavonoids in the human gut.
Gut Microbes 2016;7(3):216–234.
[60]
Jaganath IB, Mullen W, Lean ME, et al. In vitro catabolism of rutin by human fecal bacteria and the antioxidant capacity of its catabolites.
Free Radic Biol Med 2009;47(8):1180–1189.
[61]
Huang G, Lai M, Xu C, et al. Novel catabolic pathway of quercetin-3-O-rutinose-7-O-alpha-L-rhamnoside by Lactobacillus plantarum GDMCC 1.140: the direct fission of C-ring.
Front Nutr 2022;9:849439.
[62]
Tang S, Xu C, Zhou Y, et al. Akkermansia muciniphila growth promoted by lychee major flavonoid through bacteroides uniformis metabolism.
J Agric Food Chem 2024;72(44):24552–24560.
[63]
Duda-Chodak A, Tarko T, Satora P, et al. Interaction of dietary compounds, especially polyphenols, with the intestinal microbiota: a review.
Eur J Nutr 2015;54(3):325–341.
[64]
Shabbir U, Rubab M, Daliri EB, et al. Curcumin, quercetin, catechins and metabolic diseases: the role of gut microbiota.
Nutrients 2021;13(1):206.
[65]
Zhang Z, Peng X, Li S, et al. Isolation and identification of quercetin degrading bacteria from human fecal microbes.
PLoS One 2014;9(3):e90531.
[66]
Najmanova I, Pourova J, Voprsalova M, et al. Flavonoid metabolite 3-(3-hydroxyphenyl)propionic acid formed by human microflora decreases arterial blood pressure in rats.
Mol Nutr Food Res 2016;60(5):981–991.
[67]
Jensen-Kroll J, Demetrowitsch T, Sprotte S, et al. Degradation of rutin and genistein and the effect on human bacterial fecal populations of obese and non-obese.
J Funct Foods 2025;130:106930.
[68]
Serra A, Macià A, Romero M-P, et al. Metabolic pathways of the colonic metabolism of flavonoids (flavonols, flavones and flavanones) and phenolic acids.
Food Chem 2012;130(2):383–393.
[69]
Kang YG, Jang S, Kim B, et al. Inducing a synergistic anti-obesity effect by increasing the bioavailability of the flavonoid rutin with a L. plantarum strain.
Food Chem 2025;495(Pt 2):146498.
[70]
Olthof MR, Hollman PC, Buijsman MN, et al. Chlorogenic acid, quercetin-3-rutinoside and black tea phenols are extensively metabolized in humans.
J Nutr 2003;133(6):1806–1814.
[71]
Schneider H, Schwiertz A, Collins MD, et al. Anaerobic transformation of quercetin-3-glucoside by bacteria from the human intestinal tract.
Arch Microbiol 1999;171(2):81–91.
[72]
Gao A, Ni Y, Chen C, et al. Covalent binding of Geniposide metabolites to hepatic proteins: a potential mechanism for its hepatotoxicity.
Chem Biol Interact 2025;408(25):111411.
[73]
Shakya R, Nepal MR, Kang MJ, et al. Effects of intestinal microbiota on pharmacokinetics of crocin and crocetin in male Sprague-Dawley rats.
Metabolites 2020;10(11):424.
[74]
Ulusoy HG, Sanlier N. A minireview of quercetin: from its metabolism to possible mechanisms of its biological activities.
Crit Rev Food Sci Nutr 2020;60(19):3290–3303.
[75]
Guo Y, Bruno RS. Endogenous and exogenous mediators of quercetin bioavailability.
J Nutr Biochem 2015;26(3):201–210.
[76]
Bischoff SC. Quercetin: potentials in the prevention and therapy of disease.
Curr Opin Clin Nutr Metab Care 2008;11(6):733–740.
[77]
Gross M, Pfeiffer M, Martini M, et al. The quantitation of metabolites of quercetin flavonols in human urine.
Cancer Epidemiol Biomarkers Prev 1996;5(9):711–720.
[78]
Azuma K, Ippoushi K, Nakayama M, et al. Absorption of chlorogenic acid and caffeic acid in rats after oral administration.
J Agric Food Chem 2000;48(11):5496–5500.
[79]
Stalmach A, Steiling H, Williamson G, et al. Bioavailability of chlorogenic acids following acute ingestion of coffee by humans with an ileostomy.
Arch Biochem Biophys 2010;501(1):98–105.
[80]
Ogawa M, Suzuki Y, Endo Y, et al. Influence of coffee intake on urinary hippuric acid concentration.
Ind Health 2011;49(2):195–202.
[81]
Asai A, Nakano T, Takahashi M, et al. Orally administered crocetin and crocins are absorbed into blood plasma as crocetin and its glucuronide conjugates in mice.
J Agric Food Chem 2025;53(18):7302–7306.
[82]
Xi L, Qian Z, Du P, et al. Pharmacokinetic properties of crocin (crocetin digentiobiose ester) following oral administration in rats.
Phytomedicine 2007;14(9):633–636.
[83]
Lin X, Yu Z, Liu Y, et al. Gut-X axis.
Imeta 2025;4(1):e270.
[84]
Tilg H, Adolph TE, Trauner M. Gut-liver axis: pathophysiological concepts and clinical implications.
Cell Metab 2022;34(11):1700–1718.
[85]
Hsu CL, Schnabl B. The gut-liver axis and gut microbiota in health and liver disease.
Nat Rev Microbiol 2023;21(11):719–733.
[86]
Qin S, Tian J, Zhao Y, et al. Gardenia extract protects against intrahepatic cholestasis by regulating bile acid enterohepatic circulation.
J Ethnopharmacol 2024;319(Pt 1):117083.
[87]
Wang T, Tian T, Zhu Z, et al. Gardenia jasminoides Ellis. Polysaccharides alleviated cholestatic liver injury by increasing the production of butyric acid and FXR activation.
Phytother Res 2024;38(11):5363–5375.
[88]
Jin J, Zhu L, He C, et al. Genipin ameliorates cholestatic liver injury in Mdr2(-/-) mice: the role of gut microbiota modulation by its dialdehyde intermediates.
Toxicol Appl Pharmacol 2026;508:117717.
[89]
Ha S, Wong VW, Zhang X, et al. Interplay between gut microbiome, host genetic and epigenetic modifications in MASLD and MASLD-related hepatocellular carcinoma.
Gut 2024;74(1):141–152.
[90]
Benede-Ubieto R, Cubero FJ, Nevzorova YA. Breaking the barriers: the role of gut homeostasis in metabolic-associated steatotic liver disease (MASLD).
Gut Microbes 2024;16(1):2331460.
[91]
Li H, Xi Y, Xin X, et al. Correction: geniposide plus chlorogenic acid reverses non-alcoholic steatohepatitis
via regulation of gut microbiota and bile acid signaling in a mouse model in vivo.
Front Pharmacol 2025;16:1657343.
[92]
Feng Q, Liu W, Baker SS, et al. Multi-targeting therapeutic mechanisms of the Chinese herbal medicine QHD in the treatment of non-alcoholic fatty liver disease.
Oncotarget 2017;8(17):27820–27838.
[93]
Zhao T, Lun S, Yan M, et al. 6,7-Dimethoxycoumarin, Gardenoside and Rhein combination improves non-alcoholic fatty liver disease in rats.
J Ethnopharmacol 2024;322:117646.
[94]
Yi M, Fasina OB, Li Y, et al. Mixture of peanut skin extract, Geniposide, and Isoquercitrin improves the hepatic lipid accumulation of mice
via modification of gut microbiota homeostasis and the TLR4 and AMPK signaling pathways.
Int J Mol Sci 2023;24(23):16684.
[95]
Chen L, Chen C, Chen Q, et al. Deacetylasperulosidic acid methyl ester ameliorates carbon tetrachloride-induced liver fibrosis by suppressing inflammation and modulating gut microbiota.
Inflammation 2025;49(1):16.
[96]
Wang C, Jiang T, Zheng L, et al. Deacetylasperulosidic acid methyl ester attenuates liver fibrosis by modulating the SCFAs-Wnt/beta-catenin signaling axis.
Eur J Pharmacol 2026;1021:178830.
[97]
Loh JS, Mak WQ, Tan LKS, et al. Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases.
Signal Transduct Target Ther 2024;9(1):37.
[98]
Socala K, Doboszewska U, Szopa A, et al. The role of microbiotagut-brain axis in neuropsychiatric and neurological disorders.
Pharmacol Res 2021;172:105840.
[99]
Agirman G, Yu KB, Hsiao EY. Signaling inflammation across the gut-brain axis.
Science 2021;374(6571):1087–1092.
[100]
Hou Z, Sun L, Jiang Z, et al. Neuropharmacological insights into Gardenia jasminoides Ellis: harnessing therapeutic potential for central nervous system disorders.
Phytomedicine 2024;125:155374.
[101]
Liu D, Wang Q, Li Y, et al. Fructus gardeniae ameliorates anxiety- like behaviors induced by sleep deprivation
via regulating hippocampal metabolomics and gut microbiota.
Front Cell Infect Microbiol 2023;13:1167312.
[102]
Han M, Zhou Y, Gao X, et al. Modulation of gut microbiota by Gardeniae Fructus oil exerts TLR4/NF-kappaB/NLRP3 pathway-mediated antidepressant effects based on transcriptomics and fecal transplantation.
Front Pharmacol 2025;16:1635897.
[103]
Zou T, Tang X, Wang H, et al. Nanocrystalline cellulosegeniposide complex enhances gut-brain axis modulation for depression treatment.
Commun Biol 2025;8(1):667.
[104]
Liu X, He J, Cui L, et al. Limosilactobacillus reuteri-butyrate axis in depression therapy: a key pathway discovered through a novel preclinical human flora-associated animal model.
Pharmacol Res 2025;220:107941.
[105]
Xiao Q, Shu R, Wu C, et al. Crocin-I alleviates the depression-like behaviors probably
via modulating “microbiota-gut-brain” axis in mice exposed to chronic restraint stress.
J Affect Disord 2020;276:476–486.
[106]
Babu Kondaveeti S, Gupta V, Dar AA, et al. Crocetin as a neuroprotective agent: targeting western diet-induced cognitive dysfunction through antioxidant, anti-inflammatory and gut-brain axis modulation.
ASN Neuro 2026;18(1):2603409.
[107]
Chongtham A, Yoo JH, Chin TM, et al. Gut bacteria regulate the pathogenesis of Huntington's disease in drosophila model.
Front Neurosci 2022;16:902205.
[108]
Zou Z, Lei D, Wang X, et al. Crocin ameliorates cognitive impairment and pathological changes in Alzheimer's disease model mice by regulating gut microbiota.
Food Sci Nutr 2025;13(10):e71117.
[109]
Yang X, Jiang M, Wu M, et al. Crocin drives intestinal microbiota variation in a rat model of Alzheimer's disease by reducing DKK3 expression.
Brain Res 2025;1862:149734.
[110]
Wang Y, Huang B, Wei X, et al. Gut microbiota metabolic reprogramming drives the development of metabolic diseases in the host.
Gut Microbes 2026;18(1):2644681.
[111]
Cani PD, Van Hul M. Gut microbiota in overweight and obesity: crosstalk with adipose tissue.
Nat Rev Gastroenterol Hepatol 2024;21(3):164–183.
[112]
Lv C, Liu X, Chen S, et al. Extract of Gardenia jasminoides Ellis attenuates high-fat diet-induced glycolipid metabolism disorder in rats by targeting gut microbiota and TLR4/Myd88/NF-kappaB pathway.
Antioxidants (Basel) 2024;13(3):293.
[113]
Xie X, Xiao Q, Xiong Z, et al. Crocin-I ameliorates the disruption of lipid metabolism and dysbiosis of the gut microbiota induced by chronic corticosterone in mice.
Food Funct 2019;10(10):6779–6791.
[114]
Xie X, Zhang M, Sun L, et al. Crocin-I protects against high-fat diet-induced obesity
via modulation of gut microbiota and intestinal inflammation in mice.
Front Pharmacol 2022;13:894089.
[115]
Lu W, Ju W, Niu N, et al. Gardenia jasminoides Ellis polysaccharides improve gut microbiota disorder and glucose homeostasis in type 2 diabetic mice.
Fitoterapia 2026;189:107080.
[116]
Iliev ID, Ananthakrishnan AN, Guo CJ. Microbiota in inflammatory bowel disease: mechanisms of disease and therapeutic opportunities.
Nat Rev Microbiol 2025;23(8):509–524.
[117]
Shi Y, Chen Z, Fang T, et al. Gut microbiota in treating inflammatory digestive diseases: current challenges and therapeutic opportunities.
Imeta 2025;4(1):e265.
[118]
Wong CC, Yu J. Gut microbiota in colorectal cancer development and therapy.
Nat Rev Clin Oncol 2023;20(7):429–452.
[119]
Zheng BX, Yi Y, Wang XW, et al. Geniposide
via enema alleviates colitis by modulating intestinal flora and bile acid metabolites, inhibiting S100A8/S100A9/NF-kappaB, and promoting TGR5 inhibition of NLRP3 inflammasome.
Phytomedicine 2025;142:156791.
[120]
Jiang P, Zhang Y, Li X, et al. Geniposidic acid attenuates DSS-induced colitis through inhibiting inflammation and regulating gut microbiota.
Phytother Res 2023;37(8):3453–3466.
[121]
Zheng C, Zhong Y, Zhang W, et al. Chlorogenic acid ameliorates post-infectious irritable bowel syndrome by regulating extracellular vesicles of gut microbes.
Adv Sci (Weinh) 2023;10(28):e2302798.
[122]
Gholipour F, Entezar M, Amini M, et al. In vitro effects of crocin on the possible anticancer properties of Lactococcus lactis against colorectal adenocarcinoma cells.
Naunyn Schmiedebergs Arch Pharmacol 2025;398(5):5729–5741.
[123]
Khalaf EM, Hassan HM, El-Baz AM, et al. A novel therapeutic combination of dapagliflozin, Lactobacillus and crocin attenuates diabetic cardiomyopathy in rats: role of oxidative stress, gut microbiota, and PPARgamma activation.
Eur J Pharmacol 2022;931:175172.
[124]
Kim HI, Hong SH, Lee SY, et al. Gardenia Jasminoides ameliorates antibiotic-associated aggravation of DNCB-induced atopic dermatitis by restoring the intestinal microbiome profile.
Nutrients 2021;13(4):1349.
[125]
Zheng Y, Gao D, Xie H, et al. Geniposidic acid inhibits OVA-induced asthma by suppressing allergic airway inflammation and regulating gut microbiota.
Front Immunol 2025;16:1549459.
[126]
Luo N, Chen GB, Zhang T, et al. Genipin attenuates sepsisinduced splenocyte apoptosis
via the inhibition of endoplasmic reticulum stress.
Biol Pharm Bull 2023;46(2):187–193.
[127]
Li Z, Zhang TB, Jia DH, et al. Genipin inhibits the growth of human bladder cancer cells
via inactivation of PI3K/Akt signaling.
Oncol Lett 2018;15(2):2619–2624.
[128]
Liu X, Ye Z, Xiao T, et al. Genipin, a gut microbiota-derived metabolite of Xihuang Pill, suppresses triple-negative breast cancer angiogenesis by inhibiting HIF-1alpha/HSPG2 axis.
Phytother Res 2026;40(4):2125–2142.
[129]
Li M, Peng Y, Xiao Q, et al. Pharmacological inhibition of PGK1 by genipin reduces inflammation and oxidative damage in osteoarthritis.
Phytomedicine 2026;150:157729.
[130]
Hong YJ, Yang KS. Anti-inflammatory activities of crocetin derivatives from processed Gardenia jasminoides.
Arch Pharm Res 2013;36(8):933–940.
[131]
Xia T, Zhao R, He S, et al. Gardenoside ameliorates inflammation and inhibits ECM degradation in IL-1beta-treated rat chondrocytes
via suppressing NF-kappaB signaling pathways.
Biochem Biophys Res Commun 2023;640:164–172.
[132]
Shi Q, Cao J, Fang L, et al. Geniposide suppresses LPS-induced nitric oxide, PGE2 and inflammatory cytokine by downregulating NF-kappaB, MAPK and AP-1 signaling pathways in macrophages.
Int Immunopharmacol 2014;20(2):298–306.
[133]
Tangpradubkiat P, Chayanupatkul M, Werawatganone P, et al. Gardenia jasminoides extract mitigates acetaminopheninduced liver damage in mice.
BMC Complement Med Ther 2024;24(1):371.
[134]
Chen J, Tchivelekete GM, Zhou X, et al. Anti-inflammatory activities of Gardenia jasminoides extracts in retinal pigment epithelial cells and zebrafish embryos.
Exp Ther Med 2021;22(1):700.
[135]
Park SH, An JE, Jang S, et al. Gardenia jasminoides extract without crocin improved atopic dermatitis-like skin lesions
via suppression of Th2-related cytokines in Dfe-induced NC/Nga mice.
J Ethnopharmacol 2019;241:112015.
[136]
Ma S, Zhang C, Zhang Z, et al. Geniposide protects PC12 cells from lipopolysaccharide-evoked inflammatory injury
via up-regulation of miR-145-5p.
Artif Cells Nanomed Biotechnol 2019;47(1):2875–2881.
[137]
Zhao XL, Yu L, Zhang SD, et al. Cryptochlorogenic acid attenuates LPS-induced inflammatory response and oxidative stress
via upregulation of the Nrf2/HO-1 signaling pathway in RAW 264.7 macrophages.
Int Immunopharmacol 2020;83:106436.
[138]
Pu Z, Liu Y, Li C, et al. Using network pharmacology for systematic understanding of geniposide in ameliorating inflammatory responses in colitis through suppression of NLRP3 inflammasome in macrophage by AMPK/Sirt1 dependent signaling.
Am J Chin Med 2020;48(7):1693–1713.
[139]
Zhuge X, Jin X, Ji T, et al. Geniposide ameliorates dextran sulfate sodium-induced ulcerative colitis
via KEAP1-Nrf2 signaling pathway.
J Ethnopharmacol 2023;314:116626.
[140]
Zhuang GD, Gu WT, Xu SH, et al. Rapid screening of antioxidant from natural products by AAPH-incubating HPLC-DAD-HR MS/MS method: a case study of Gardenia jasminoides fruit.
Food Chem 2023;401:134091.
[141]
Zhou S, Sun Y, Zhao K, et al. miR-21/PTEN pathway mediates the cardioprotection of geniposide against oxidized low-density lipoprotein-induced endothelial injury
via suppressing oxidative stress and inflammatory response.
Int J Mol Med 2020;45(5):1305–1316.
[142]
Shen B, Feng H, Cheng J, et al. Geniposide alleviates non-alcohol fatty liver disease
via regulating Nrf2/AMPK/mTOR signalling pathways.
J Cell Mol Med 2020;24(9):5097–5108.
[143]
Han YL, Yan TT, Li HX, et al. Geniposide alleviates heart failure with preserved ejection fraction in mice by regulating cardiac oxidative stress
via MMP2/SIRT1/GSK3beta pathway.
Acta Pharmacol Sin 2024;45(12):2567–2578.
[144]
Dong L, Zhang H, Wang K, et al. Carbon dots extracted from the plant Gardenia jasminoides ameliorates ischemia- reperfusion injury.
Pharmaceuticals (Basel) 2025;18(6):870.
[145]
Im M, Kim A, Ma JY. Ethanol extract of baked Gardeniae Fructus exhibits in vitro and in vivo anti-metastatic and anti-angiogenic activities in malignant cancer cells: role of suppression of the NF-kappaB and HIF-1alpha pathways.
Int J Oncol 2016;49(6):2377–2386.
[146]
Bai G, Chen B, Xiao X, et al. Geniposide inhibits cell proliferation and migration in human oral squamous carcinoma cells
via AMPK and JNK signaling pathways.
Exp Ther Med 2022;24(6):706.
[147]
He H, Li Y, Wang Y, et al. Geniposide inhibits non-small cell lung cancer by regulating proliferation, apoptosis, invasion, migration, epithelial-mesenchymal transition, and cancer stemlike cell property
via Wnt/beta-catenin pathway.
Biochem Genet 2026;64(1):707–726.
[148]
Lin P, Yue W, Xiang H, et al. Investigating the effects of gardenia polysaccharides on LPS-induced immune injury in mice and exploring the molecular mechanisms underlying its regulatory effect on the immune function of macrophages.
Foods 2025;14(20):3455.
[149]
Nazir MM, Ashraf A, Nazir MM, et al. Anti-arthritic and immunomodulatory effects of geniposide: a systematic review and meta-analysis of preclinical studies.
Inflammopharmacology 2025;33(8):4499–4518.
[150]
Huang M, Jiang J, Li YJ, et al. Exploring the anti- inflammatory mechanism of geniposide in rheumatoid arthritis
via network pharmacology and experimental validation.
Sci Rep 2025;15(1):24812.
[151]
Park SH, Song HK, Ji KY, et al. Topical administration of gardenia jasminoides extract regulates Th2 immunity in OVA-induced mice.
Cells 2023;12(6):941.
[152]
Sun L, Hou Z, Wang W, et al. Processing-induced changes in neuroprotective components and mechanisms of Gardeniae fructus: integrating UPLC-Q-TOF-MS/MS, network pharmacology, and in vitro analysis.
Bioresour Bioprocess 2026;13(1):10.
[153]
Zhang W, Zhang F, Hu Q, et al. The emerging possibility of the use of geniposide in the treatment of cerebral diseases: a review.
Chin Med 2021;16(1):86.
[154]
Zhao Y, Liu X, Yang S, et al. Electrochemical biosensors with right-side-out-oriented cell membrane coating for the evaluation of AChE inhibitors as potential anti-Alzheimer's disease agents.
Acta Pharm Sin B 2025;15(11):5988–6000.
[155]
Xiao Y, Gu L, Zhang W, et al. Identification of Prolyl endopeptidase as a novel anti-depression target of Genipin-1-b-D-gentiobioside in brain tissues.
Behav Brain Res 2025;484:115511.
[156]
Zheng M, Li K, Chen T, et al. Geniposide protects depression through BTK/JAK2/STAT1 signaling pathway in lipopolysaccharideinduced depressive mice.
Brain Res Bull 2021;170:65–73.
[157]
Wang M, Yang L, Chen Z, et al. Geniposide ameliorates chronic unpredictable mild stress induced depression-like behavior through inhibition of ceramide-PP2A signaling
via the PI3K/Akt/GSK3beta axis.
Psychopharmacology (Berl) 2021;238(10):2789–2800.
[158]
Liu J, Zhang Y, Deng X, et al. Geniposide decreases the level of Abeta1-42 in the hippocampus of streptozotocin- induced diabetic rats.
Acta Biochim Biophys Sin (Shanghai) 2013;45(9):787–791.
[159]
Lv C, Wang L, Liu X, et al. Geniposide attenuates oligomeric Abeta(1-42)-induced inflammatory response by targeting RAGE-dependent signaling in BV2 cells.
Curr Alzheimer Res 2014;11(5):430–440.
[160]
Wang Y, Gong Q, Pan H, et al. Gardenia jasminoides J. Ellis extract attenuates memory impairment in rats with Alzheimer's disease by suppressing NLRP3 inflammasome.
Brain Res 2024;1824:148687.
[161]
Zang CX, Bao XQ, Li L, et al. The protective effects of Gardenia jasminoides (Fructus Gardenia) on amyloid-beta-induced mouse cognitive impairment and neurotoxicity.
Am J Chin Med 2018;46(2):389–405.
[162]
Taheri R, Hadipour E, Tayarani-Najaran Z. Crocin protects against beta-amyloid peptide-induced apoptosis in PC12 cells
via the PI3 K pathway.
Curr Mol Pharmacol 2021;14(4):627–634.
[163]
Chen Y, Zhang Y, Li L, et al. Neuroprotective effects of geniposide in the MPTP mouse model of Parkinson's disease.
Eur J Pharmacol 2015;768:21–27.
[164]
Salama RM, Abdel-Latif GA, Abbas SS, et al. Neuroprotective effect of crocin against rotenone-induced Parkinson's disease in rats: interplay between PI3K/Akt/mTOR signaling pathway and enhanced expression of miRNA-7 and miRNA-221.
Neuropharmacology 2020;164:107900.
[165]
Chen W, Wang H, Ye X, et al. Gardenia-derived extracellular vesicles exert therapeutic effects on dopaminergic neuron apoptosis-mediated Parkinson's disease.
NPJ Parkinson's Dis 2025;11(1):200.
[166]
Sun Q, Zhang X, Fan J, et al. Geniposide protected against cerebral ischemic injury through the anti-inflammatory effect
via the NF-kappaB signaling pathway.
Transl Neurosci 2023;14(1):20220273.
[167]
Li F, Li W, Li X, et al. Geniposide attenuates inflammatory response by suppressing P2Y14 receptor and downstream ERK1/2 signaling pathway in oxygen and glucose deprivationinduced brain microvascular endothelial cells.
J Ethnopharmacol 2016;185:77–86.
[168]
An B, Ma Y, Xu Y, et al. Crocin regulates the proliferation and migration of neural stem cells after cerebral ischemia by activating the Notch1 pathway.
Folia Neuropathol 2020;58(3):201–212.
[169]
Sun M, Yuan Z, Li M, et al. Gardeniae Fructus extract terminates refractory status epilepticus with a wide time window through inhibiting neuroinflammation.
Phytomedicine 2025;142:156770.
[170]
Chen T, Ai L, Shuang R, et al. Shanzhiside methyl ester attenuated cognitive impairment in diabetic mice by inhibiting neuroinflammation and glycolysis
via HSP90AA1/HIF1A/STAT1.
Phytomedicine 2025;146:157103.
[171]
Cao Q, Du X, Liu A, et al. Iridoids in gardenia fruit: key components in liver disease therapy.
Front Nutr 2025;12:1667863.
[172]
Zhang Q, Li Z, Wang L. A potential herbal component for the future treatment of fatty liver disease: geniposide from gardenia.
Front Pharmacol 2025;16:1610676.
[173]
Cai Y, Fang L, Chen F, et al. Targeting AMPK related signaling pathways: a feasible approach for natural herbal medicines to intervene non-alcoholic fatty liver disease.
J Pharm Anal 2025;15(1):101052.
[174]
Li Z, Yang L, Kong L, et al. Drug innovation
via integration of traditional Chinese and Western medicine.
Sci Tradit Chin Med 2025;3(2):97–112.
[175]
Suttawong N, Witayavanitkul N, Chayanupatkul M, et al. Gardenia jasminoides fruit extract ameliorates non-alcoholic steatohepatitis with fibrosis by modulating inflammatory and fibrogenic pathways.
PLoS One 2025;20(10):e0333800.
[176]
Qin T, Hasnat M, Wang Z, et al. Geniposide alleviated bile acid-associated NLRP3 inflammasome activation by regulating SIRT1/FXR signaling in bile duct ligation-induced liver fibrosis.
Phytomedicine 2023;118:154971.
[177]
Song M, Chen Z, Qiu R, et al. Inhibition of NLRP3-mediated crosstalk between hepatocytes and liver macrophages by geniposidic acid alleviates cholestatic liver inflammatory injury.
Redox Biol 2022;55:102404.
[178]
Zhou Y, Feng M, Hai H, et al. Geniposidic acid alleviated metabolic dysfunction-associated steatotic liver disease by exciting SIRT6 signaling.
Phytomedicine 2025;146:157140.
[179]
Fan M, Xu Y, Wu B, et al. Geniposidic acid targeting FXR “S332 and H447” mediated conformational change to upregulate CYPs and miR-19a-3p to ameliorate drug-induced liver injury.
Adv Sci (Weinh) 2025;12(15):e2409107.
[180]
Li H, Yang DH, Zhang Y, et al. Geniposide suppresses NLRP3 inflammasome-mediated pyroptosis
via the AMPK signaling pathway to mitigate myocardial ischemia/reperfusion injury.
Chin Med 2022;17(1):73.
[181]
Choi PG, Park SH, Jeong HY, et al. Geniposide attenuates muscle atrophy
via the inhibition of FoxO1 in senescence- accelerated mouse prone-8.
Phytomedicine 2024;123:155281.
[182]
Zhu Z, Mo S, Luo J, et al. Impact of gardenia extract on coagulation function in rats with acute myocardial ischemia model.
Thromb J 2025;23(1):80.
[183]
Shi R, Liu MQ, Xiao JP, et al. Geniposide alleviates kidney fibrosis by targeting STAT3-HK2-mediated glycolysis.
BMC Complement Med Ther 2025;25(1):365.
[184]
Gao J, Long Y, Li J, et al. Geniposide, a potential therapeutical candidate for acute pancreatitis, inhibited trypsinogen-activated CBS degradation and remodeled transsulfuration metabolic flux.
Redox Biol 2025;88:103900.
[185]
Li Y, Ji X, Ding T, et al. Novel mechanism by which geniposide alleviates rheumatoid arthritis: targeted inhibition of SphK1 negatively regulates S1P signaling, promotes HIF-1alpha acetylation- mediated degradation and blocks the VEGF-induced synovial angiogenesis.
Phytomedicine 2026;150:157739.
[186]
Lin J, Wang X, Gu M, et al. Geniposide ameliorates atherosclerosis by restoring lipophagy
via suppressing PARP1/PI3K/AKT signaling pathway.
Phytomedicine 2024;129:155617.
[187]
Tian J, Yi Y, Zhao Y, et al. Oral chronic toxicity study of geniposide in rats.
J Ethnopharmacol 2018;213:166–175.
[188]
Zeng X, Jiang J, Liu S, et al. Bidirectional effects of geniposide in liver injury: preclinical evidence construction based on meta-analysis.
J Ethnopharmacol 2024;319:117061.
[189]
Tang Q, Yu Q, Ni B, et al. Dual effects of Psoraleae Fructus on the liver: hepatoprotection or hepatoxicity?
Acupunct Herb Med 2024;4(2):176–183.
[190]
Gao Y, Zhou T. Depressive disorder prevention by DIET crosslink: diet, intestinal microbiota, enzyme and traits of metabolism.
Trends Food Sci Technol 2024;150:104596.
[191]
Ding Y, Zhang T, Tao JS, et al. Potential hepatotoxicity of geniposide, the major iridoid glycoside in dried ripe fruits of Gardenia jasminoides (Zhi-zi).
Nat Prod Res 2013;27(10):929–933.
[192]
Luo Y, Zhang X, Zhang W, et al. Compatibility with Semen Sojae Praeparatum attenuates hepatotoxicity of Gardeniae Fructus by regulating the microbiota, promoting butyrate production and activating antioxidant response.
Phytomedicine 2021;90:153656.
[193]
Jin Z, Cheng S, Liu B, et al. Geniposide induces hepatotoxicity
via the bile acid-induced activation of NLRP3 inflammasome and regulation of the FXR/PERK/TXNIP pathway.
Toxicol Lett 2025;413:111740.
[194]
Cheng S, Liu B, Jin Z, et al. Geniposide activates the NLRP3 inflammasome pathway to induce nephrotoxicity by regulating FXR/PERK/TXNIP pathways.
Toxicon 2026;269:108661.
[195]
Fan X, Lin L, Cui B, et al. Therapeutic potential of genipin in various acute liver injury, fulminant hepatitis, NAFLD and other non-cancer liver diseases: more friend than foe.
Pharmacol Res 2020;159:104945.
[196]
Kang MJ, Khanal T, Kim HG, et al. Role of metabolism by human intestinal microflora in geniposide-induced toxicity in HepG2 cells.
Arch Pharm Res 2012;35(4):733–738.
[197]
Ozaki A, Kitano M, Furusawa N, et al. Genotoxicity of gardenia yellow and its components.
Food Chem Toxicol 2002;40(11):1603–1610.
[198]
Qiu J, Lin C, Ren G, et al. Geniposide dosage and administration time: balancing therapeutic benefits and adverse reactions in liver disease treatment.
Phytomedicine 2024;132:155799.
[199]
Guo H, Liu X, Jiang Y, et al. Characterization and quantification of the Chinese medical formula Zhi-Zi-Chi decoction, a systematic strategy for the attenuation and synergy of compatibility mechanism.
J Pharm Biomed Anal 2023;223:115130.
[200]
Clarke G, Sandhu KV, Griffin BT, et al. Gut reactions: breaking down xenobiotic-microbiome interactions.
Pharmacol Rev 2019;71(2):198–224.
[201]
Feng W, Liu J, Ao H, et al. Targeting gut microbiota for precision medicine: focusing on the efficacy and toxicity of drugs.
Theranostics 2020;10(24):11278–11301.
[202]
Zhao Q, Chen Y, Huang W, et al. Drug-microbiota interactions: an emerging priority for precision medicine.
Signal Transduct Target Ther 2023;8(1):386.
[203]
Amedei A, Boem F. I’ve gut A feeling: microbiota impacting the conceptual and experimental perspectives of personalized medicine.
Int J Mol Sci 2018;19(12):3756.
[204]
Petrosino JF. The microbiome in precision medicine: the way forward.
Genome Med 2018;10(1):12.
[205]
Behrouzi A, Nafari AH, Siadat SD. The significance of microbiome in personalized medicine.
Clin Transl Med 2019;8(1):16.
[206]
Zmora N, Zeevi D, Korem T, et al. Taking it personally: personalized utilization of the human microbiome in health and disease.
Cell Host Microbe 2016;19(1):12–20.
[207]
Lam KN, Alexander M, Turnbaugh PJ. Precision medicine goes microscopic: engineering the microbiome to improve drug outcomes.
Cell Host Microbe 2019;26(1):22–34.
[208]
Xavier JB. Ecological management of the microbiota in patients with cancer.
Nat Rev Clin Oncol 2025;22(9):627–639.
[209]
Wang J, Zhou T. Unveiling gut microbiota's role: bidirectional regulation of drug transport for improved safety.
Med Res Rev 2025;45(1):311–343.
[210]
Tsutsumi K, Yonehara R, Ishizaka-Ikeda E, et al. Structures of the wild-type MexAB-OprM tripartite pump reveal its complex formation and drug efflux mechanism.
Nat Commun 2019;10(1):1520.
[211]
Haiser HJ, Gootenberg DB, Chatman K, et al. Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta.
Science 2013;341(6143):295–298.
[212]
Taur Y, Coyte K, Schluter J, et al. Reconstitution of the gut microbiota of antibiotic-treated patients by autologous fecal microbiota transplant.
Sci Transl Med 2018;10(460):eaap9489.
[213]
Davar D, Dzutsev AK, McCulloch JA, et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients.
Science 2021;371(6529):595–602.
[214]
Baruch EN, Youngster I, Ben-Betzalel G, et al. Fecal microbiota transplant promotes response in immunotherapy-refractory mel-anoma patients.
Science 2021;371(6529):602–609.
[215]
Stein RR, Tanoue T, Szabady RL, et al. Computer-guided design of optimal microbial consortia for immune system modulation.
Elife 2018;7:e30916.
[216]
Canale FP, Basso C, Antonini G, et al. Metabolic modulation of tumours with engineered bacteria for immunotherapy.
Nature 2021;598(7882):662–666.
[217]
Lancaster SM, Lee-McMullen B, Abbott CW, et al. Global, distinctive, and personal changes in molecular and microbial profiles by specific fibers in humans.
Cell Host Microbe 2022;30(6):848–862.e7.
Year 2026 volume 6 Issue 3
PDF
8
1
Cite this Article
BibTeX
Article Info
doi: 10.1097/HM9.0000000000000211
- Receive Date：2026-07-10
- Online Date：2026-11-04
- Published：2026-09-25
关闭全屏
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62662699(Operation and Technical Support)
qkjq@cast.org.cn
