Midlife intervention of Dendrobium officinale extract modulates gut microbiota to activate InR-Nrf2 axis, promoting intestinal health and longevity

doi:10.3748/wjg.v32.i23.117238

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Jun 21, 2026; 32(23): 117238
Published online Jun 21, 2026. doi: 10.3748/wjg.v32.i23.117238

Midlife intervention of Dendrobium officinale extract modulates gut microbiota to activate InR-Nrf2 axis, promoting intestinal health and longevity

Chen-Rong Jin, Jiao Xi, Si-Ming Wang, Si-Yu Zhang, Shi-Ting Yu, Dai-An Pan, Da-Qing Zhao, Zheng-Qi Dong, Shi-Chao Liu, Mei-Chen Liu

Chen-Rong Jin, Jiao Xi, Si-Ming Wang, Si-Yu Zhang, Shi-Ting Yu, Dai-An Pan, Da-Qing Zhao, Mei-Chen Liu, Northeast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130000, Jilin Province, China

Zheng-Qi Dong, State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Chinese Academy of Medical Sciences and Peking Union Medical College, Institute of Medicinal Plant Development, Beijing 100193, China

Shi-Chao Liu, School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130000, Jilin Province, China

Author contributions: Jin CR contributed to writing the original draft, methodology, formal analysis, and data curation; Xi J and Wang SM contributed to validation, methodology, data curation; Zhang SY and Yu ST contributed to methodology, formal analysis; Pan DA contributed to formal analysis and data curation; Zhao DQ contributed to visualization, validation; Dong ZQ contributed to validation, formal analysis; Liu SC contributed to writing-review and editing; Liu MC contributed to writing-review and editing, supervision, project administration, funding acquisition, conceptualization.

Supported by the Scientific and Technological Development Planning Foundation of Jilin Province, No. YDZJ202401009ZYTS; National Natural Science Foundation of China, No. 82404836; and the Scientific and Technological Developing Scheme of Jilin Province, No. 20210304002YY and No. 20210204188YY.

Institutional review board statement: Ethical review and approval were waived for this study because it exclusively utilized commercially available, well-established human cell lines. These cell lines are publicly accessible from recognized biological resource centers, and their use does not constitute research involving human subjects as defined by institutional and national guidelines. No primary human tissue, identifiable personal data, or direct interaction with human participants was involved.

Institutional animal care and use committee statement: This study utilized established invertebrate model organisms (Drosophila melanogaster, Caenorhabditis elegans) and human cell lines. Research involving Drosophila melanogaster and Caenorhabditis elegans does not require approval from an institutional ethics committee. All human cell lines used in this study are widely used and well-documented in the scientific community. The research was conducted in accordance with all relevant institutional biosafety guidelines and regulations.

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

Data sharing statement: The data supporting this article have been included within the manuscript. All relevant data are available upon request from the corresponding author.

Corresponding author: Mei-Chen Liu, PhD, Doctor, Northeast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, No. 1035 Boshuo Road, Changchun 130000, Jilin Province, China. liumc@ccucm.edu.cn

Received: December 5, 2025
Revised: January 28, 2026
Accepted: March 19, 2026
Published online: June 21, 2026
Processing time: 188 Days and 17.1 Hours

Abstract

BACKGROUND

Dendrobium officinale (D. officinale) is a traditional Chinese herb that has been studied extensively for its medicinal properties, including gastrointestinal protection, anti-aging effects, and antioxidant properties. However, the molecular mechanisms by which D. officinale delays aging have not been fully elucidated.

AIM

To investigate the effects of D. officinale extract (DOE) on extending healthy lifespan through the maintenance of intestinal homeostasis, and to explore its intervention window, molecular mechanism, and key components.

METHODS

Based on evaluation systems using human MRC-5 cells, Caenorhabditis elegans, and Drosophila melanogaster, the optimal spatiotemporal intervention window for DOE was determined. Its effects on aging-related markers and stress resistance were assessed. (16S) rDNA sequencing, bioinformatics, immunofluorescence staining, reintroduction of dominant strains, and in vivo gene knockdown strategies were applied to identify and validate potential targets.

RESULTS

We determined that midlife is the optimal intervention window for DOE to extend healthy lifespan. Intervention at this stage delayed the age-related decline in health indicators, including motor and intestinal functions as well as oxidative stress. Mechanistically, DOE remodeled the gut microbiota in a sex-specific microbe host pairing, favoring Acetobacter pomorum in females and Lactobacillus plantarum in males, which differentially regulated glucose and lipid metabolism in both sexes. This remodeling modulated the insulin/insulin-like growth factor-1 signaling pathway, thereby activating the Keap1-Nrf2-antioxidant response element antioxidant signaling pathway. The enhanced antioxidant defense ultimately contributed to the prolonged healthy lifespan. In addition, D. officinale polysaccharide was identified as a potential core component of DOE’s pharmacological activity.

CONCLUSION

DOE regulated the microbiota-InR-Nrf2 axis to counteract oxidative stress, thereby maintaining intestinal function and extending healthy lifespan. These findings provide a molecular basis for the discovery of new antioxidants and anti-aging agents.

Keywords: Aging; Antioxidants; Caenorhabditis elegans; Drosophila melanogaster; Gut microbiota

Core Tip: Dendrobium officinale extract intervention during middle age is the optimal window for cross-species conservation of its benefits, delaying degeneration and extending lifespan. It maintains intestinal stem cell homeostasis and remodels gut microbiota, promoting gender-specific microbe-host pairings (Acetobacter pomorum in females, Lactobacillus plantarum in males) to modulate metabolic differences. This reshaped microbiota activates the InR-Nrf2 axis, antagonizing oxidative stress, ensuring intestinal homeostasis, and prolonging health span.