Integrated 'omics analysis for the gut microbiota response to moxibustion in a rat model of chronic fatigue syndrome.

L I Chaoran, Yang Yan, Feng Chuwen, L I Heng, Q U Yuanyuan, Wang Yulin, Wang Delong, Wang Qingyong, Guo Jing, Shi Tianyu, Sun Xiaowei, Wang Xue, Hou Yunlong, Sun Zhongren, Yang Tiansong
Author Information
  1. L I Chaoran: Department of Acupuncture, Zhejiang Chinese Medical University, Hangzhou 310000, China.
  2. Yang Yan: Department of Chinese Medical Literature, College of Basic Medicine, Heilongjiang University of Chinese medicine, Harbin 150040, China.
  3. Feng Chuwen: Department of Rehabilitation, the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, China.
  4. L I Heng: Shanghai Applied Protein Technology Co., Ltd., Shanghai 200233, China.
  5. Q U Yuanyuan: Graduate School, the Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, China.
  6. Wang Yulin: Department of Acupuncture, the Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, China.
  7. Wang Delong: Department of Acupuncture, the Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, China.
  8. Wang Qingyong: Graduate School, the Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, China.
  9. Guo Jing: Graduate School, the Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, China.
  10. Shi Tianyu: Graduate School, the Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, China.
  11. Sun Xiaowei: Department of Acupuncture, the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, China.
  12. Wang Xue: Department of Acupuncture, Chongqing Changshou District People's Hospital, Chongqing 401220, China.
  13. Hou Yunlong: College of integrated Chinese and Western Medicine, Hebei University of Chinese Medicine, and National Key Laboratory of Collateral Disease Research and Innovative Chinese Medicine, Hebei 050000, China.
  14. Sun Zhongren: Department of Acupuncture, the Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, China.
  15. Yang Tiansong: 10 Department of Rehabilitation, the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, and Traditional Chinese Medicine Informatics Key Laboratory of Heilongjiang Province, Harbin 150040, China.

Abstract

OBJECTIVE: To observe the efficacy of moxibustion in the treatment of chronic fatigue syndrome (CFS) and explore the effects on gut microbiota and metabolic profiles.
METHODS: Forty-eight male Sprague-Dawley rats were randomly assigned to control group (Con), CFS model group (Mod, established by multiple chronic stress for 35 d), MoxA group (CFS model with moxibustion Shenque (CV8) and Guanyuan (CV4), 10 min/d, 28 d) and MoxB group (CFS model with moxibustion Zusanli (ST36), 10 min/d, 28 d). Open-field test (OFT) and Morris-water-maze test (MWMT) were determined for assessment the CFS model and the therapeutic effects of moxibustion.16S rRNA gene sequencing analysis based gut microbiota integrated untargeted liquid chromatograph-mass spectrometer (LC-MS) based fecal metabolomics were executed, as well as Spearman correlation analysis, was utilized to uncover the functional relevance between the potential metabolites and gut microbiota.
RESULTS: The results of our behavioral tests showed that moxibustion improved the performance of CFS rats in the OFT and the MWMT. Microbiome profiling analysis revealed that the gut microbiomes of CFS rats were less diverse with altered composition, including increases in pro-inflammatory species (such as Proteobacteria) and decreases in anti-inflammatory species (such as Bacteroides, Lactobacillus, Ruminococcus, and Prevotella). Moxibustion partially normalized these changes in the gut microbiota. Furthermore, CFS was associated with metabolic disorders, which were effectively ameliorated by moxibustion. This was demonstrated by the normalization of 33 microbiota-related metabolites, including mannose ( 0.001), aspartic acid ( 0.009), alanine ( 0.007), serine ( 0.000), threonine ( 0.027), methionine ( 0.023), 5-hydroxytryptamine ( 0.008), alpha-linolenic acid ( 0.003), eicosapentaenoic acid ( 0.006), hypoxanthine ( 0.000), vitamin B6 ( 0.000), cholic acid ( 0.013), and taurocholate ( 0.002). Correlation analysis showed a significant association between the perturbed fecal microbiota and metabolite levels, with a notable negative relationship between LCA and Bacteroides.
CONCLUSIONS: In this study, we demonstrated that moxibustion has an antifatigue-like effect. The results from the 16S rRNA gene sequencing and metabolomics analysis suggest that the therapeutic effects of moxibustion on CFS are related to the regulation of gut microorganisms and their metabolites. The increase in Bacteroides and decrease in LCA may be key targets for the moxibustion treatment of CFS.

Keywords

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Grants

  1. 81873378/Mechanism Study on Electroacupuncture Regulating MDM2 Ubiquitination PSD-95 Level and Remodeling Synaptic Structure of Hippocampal Neurons to Improve Cognitive Dysfunction in CFS
  2. 2021RCZXZK02/Study on the Mechanism of Moxibustion Regulating the Gut Microbiota of Chronic Fatigue Syndrome Targeting the 5-HT Signal System
  3. 2019BS03/Based on Gut Microbiota and Metabolism to Study the Mechanism in the Treatment of Chronic Fatigue Syndrome by Moxibustion
  4. ZHY2022-136/The Mechanism of Electroacupuncture Improving Hippocampal Synaptic Plasticity in CFS Cognitive Dysfunction Rats
  5. 81704170/Based on TGF-β/Smad Signaling Pathway to Studying the Role and Mechanism of NF-κB in the Treatment of Chronic Fatigue Syndrome with Electroacupuncture
  6. ZS21ZA08/Study on the Mechanism of Moxibustion Repairing the Barrier Function-Inflammatory Response of Chronic Fatigue Syndrome by the Gut-Brain Axis
  7. LH2020H092/Study on the Mechanism of Electroacupuncture Adjusting Gut Microbiota to Improve Oxidative Inflammatory Response in the Treatment of Chronic Fatigue Syndrome
  8. LBH-Q18117/Experimental Study on Electroacupuncture Improving Protein Expression Differences and Target Effects in Hippocampus and Hypothalamus of Rats with Chronic Fatigue Syndrome
  9. IIR 16-003/HSRD VA
  10. ZHY2020-79/Study on the Effect and Mechanism of Moxibustion on Gut Microbiota in Rats with Chronic Fatigue Syndrome
  11. ZHY16-003/The Mechanism of TGF-β/ Smad Mediated NF- κB Inflammatory Pathway in the Treatment of Chronic Fatigue Syndrome by Electroacupuncture

MeSH Term

Rats
Male
Animals
Gastrointestinal Microbiome
Rats, Sprague-Dawley
Moxibustion
Fatigue Syndrome, Chronic
RNA, Ribosomal, 16S
Metabolomics

Chemicals

RNA, Ribosomal, 16S

Word Cloud

Created with Highcharts 10.0.00moxibustionCFSgutmicrobiotaanalysismodelchronicgroupacidfatiguesyndromeeffectsratsd16SrRNAgenesequencingmetabolomicsmetabolitesBacteroides000treatmentmetabolic10min/d28testOFTMWMTtherapeuticbasedfecalresultsshowedincludingspeciesdemonstratedLCAOBJECTIVE:observeefficacyexploreprofilesMETHODS:Forty-eightmaleSprague-DawleyrandomlyassignedcontrolConModestablishedmultiplestress35MoxAShenqueCV8GuanyuanCV4MoxBZusanliST36Open-fieldMorris-water-mazedeterminedassessmentintegrateduntargetedliquidchromatograph-massspectrometerLC-MSexecutedwellSpearmancorrelationutilizeduncoverfunctionalrelevancepotentialRESULTS:behavioraltestsimprovedperformanceMicrobiomeprofilingrevealedmicrobiomeslessdiversealteredcompositionincreasespro-inflammatoryProteobacteriadecreasesanti-inflammatoryLactobacillusRuminococcusPrevotellaMoxibustionpartiallynormalizedchangesFurthermoreassociateddisorderseffectivelyamelioratednormalization33microbiota-relatedmannose001aspartic009alanine007serinethreonine027methionine0235-hydroxytryptamine008alpha-linolenic003eicosapentaenoic006hypoxanthinevitaminB6cholic013taurocholate002CorrelationsignificantassociationperturbedmetabolitelevelsnotablenegativerelationshipCONCLUSIONS:studyantifatigue-likeeffectsuggestrelatedregulationmicroorganismsincreasedecreasemaykeytargetsIntegrated'omicsresponseratgastrointestinalmicrobiome

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