Review Article

Split Viewer

Journal of Acupuncture Research 2023; 40(2): 129-134

Published online May 31, 2023

https://doi.org/10.13045/jar.2023.00094

© Korean Acupuncture & Moxibustion Medicine Society

Research Trends of Acupuncture-Related Therapy on Microbiome in Musculoskeletal Disorders

Joo-Hee Kim

Department of Acupuncture and Moxibustion Medicine, College of Korean Medicine, Sangji University, Wonju, Korea

Correspondence to : Joo-Hee Kim
Department of Acupuncture and Moxibustion Medicine, College of Korean Medicine, Sangji University, 83 Sangjidae-gil, Wonju 26339, Korea
E-mail: jhkim714v@gmail.com

Received: May 9, 2023; Revised: May 11, 2023; Accepted: May 15, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

In this review, we searched for clinical and experimental studies related to acupuncture-related therapy (ART) on the microbiome in musculoskeletal disorders (MSDs) through the electronic databases of MEDLINE via PubMed, EMBASE, and Oriental Medicine Advanced Searching Integrated System up to May 2023, without language restriction, and after the selection/exclusion process, the study design, target disease, intervention details, treatment period, outcomes, and study results were extracted. A total of 8 articles were selected. Two randomized controlled trials and 6 animal studies evaluated knee osteoarthritis, rheumatoid arthritis, spinal cord injury, ankylosing spondylitis, and osteoporosis. ART, including electroacupuncture, thread-embedding acupuncture, and moxibustion, affected microbiome modulation in MSDs. The results reveal that ART could be a potential treatment for regulating the microbiome in MSDs. However, further high-quality studies are needed.

Keywords Acupuncture; Microbiome; Musculoskeletal disorders; Research trends

Musculoskeletal disorders (MSDs), medical conditions that can affect the muscles, bones, joints, ligaments, tendons, nerves, and other connective tissues, are one of the most common causes of physical disability and morbidity. The global burden of MSDs, including osteoarthritis (OA), rheumatoid arthritis (RA), and lower back pain, on the healthcare system and individuals has increased significantly [1,2]. MSDs are multifactorial diseases with aging and genetic and environmental components. A recent study reported that intestinal microbiota and its derived metabolites are associated with the initiation and progression of various MSDs, including osteoporosis, OA, and RA [3].

The microbiome is defined as the collection of all microorganisms and their genomes residing in a given environment including the human body [4]. With the development of next-generation sequencing technologies and advanced computational tools, accumulating evidence shows that the microbiome may play a crucial role directly or indirectly in the pathogenesis of various diseases [5]. The interaction between the host and the microbiome is disturbed in Crohn’s disease [6]. A study also reported on the interaction between high salt intake causing hypertension and the gut–immune axis and the potential role of the gut microbiome [7]. In addition, several studies have demonstrated that the gut microbiome acts on MSDs by modulating gut permeability, hormonal secretion, immune response, and so on [8].

Acupuncture, the most popular traditional Korean medicine modality, has been effectively and safely used for treating various diseases including MSDs. Some studies have shown that acupuncture not only improves clinical symptoms but also changes the intestinal microflora in various diseases, including poststroke depression [9], cancer-related fatigue [10], irritable bowel syndrome [11], and Crohn’s disease [12]. However, no review has reported the effect of acupuncture on the microbiome in MSDs.

Therefore, this study aimed to review the clinical and animal model literature related to acupuncture therapy on microbiome in MSDs and analyze the research trends for further study.

1. Databases and search methods

A literature search was conducted using the databases of MEDLINE via PubMed, EMBASE, and Oriental Medicine Advanced Searching Integrated System (OASIS) up to May 2023. The search terms combined multiple free texts including Medical Subject Headings terms related to microbiome and acupuncture with Boolean operators. The search strategies were also adjusted for each database as appropriate. Language restriction was not implemented.

2. Inclusion and exclusion

This review included both human and animal model studies that have evaluated the effect of acupuncture on the microbiome in MSDs. In clinical literature, the study design was limited to randomized controlled trials. Interventions included all kinds of acupuncture-related therapy (ART), nonpharmacological Korean medicine treatments such as moxibustion, thread-embedding acupuncture, manual acupuncture, and electroacupuncture (EA).

Review papers were excluded; however, in the case of acupuncture review papers on the microbiome, the list of the included studies was reviewed to see if the literature on MSDs was included. Two researchers (JHK and HJY) independently performed the selection of the searched studies for eligibility. After screening the title and abstract to remove obviously irrelevant studies, the full text was examined to confirm the eligibility criteria.

3. Data extraction

Full texts of the selected studies were reviewed, and the author, publication year, study design, disease type, interventions on the treatment and control groups, and microbiome results were extracted according to a predetermined extraction form.

1. Study search results

A total of 490 studies were retrieved from PubMed (n = 144), EMBASE (n = 319), and OASIS (n = 27). After removing duplicates, 303 papers were reviewed after eligibility, and 8 were finally selected for review (Fig. 1).

Fig. 1. Flowchart of the study selection process according to PRISMA. OASIS, Oriental Medicine Advanced Searching Integrated System; PRISMA, Preferred Reporting Items for Systematic reviews and Meta-Analyses.

2. Characteristics of the included studies

By publication year, 1 study was published in 2020, 5 in 2021, and 2 in 2022 among the 8 studies. In addition, 2 articles were human studies, and 6 were animal studies. The characteristics of the included studies and microbiome modulation results are shown in Tables 1 [13,14] and 2 [15-20].

Table 1 . Characteristics of the included human studies

StudyStudy designDiseaseGroups (n)Intervention duration (wk)Clinical outcomesModulation on microbiome
Wang et al. [13] (2021)RCTKOAEA (30), sham EA (30), healthy (30)8WOMAC, NRS, response rateThe abundances of Bacteroides, Agathobacter increased/Streptococcus decreased.
Sun et al. [14] (2021)RCTASMT (9), healthy (9)4BASDAI, BASFI, VASThe abundances of Bacteroides, Prevotella decreased/Lactobacillus increased.

AS, ankylosing spondylitis; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; EA, electroacupuncture; KOA, knee osteoarthritis; MT, moxibustion; NRS, Numerical Rating Scale; RCT, randomized controlled trial; VAS, visual analog scale; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.



3. Classification by disease type

Among the 8 articles included in this review that evaluated MSDs, 3 studies focused on knee OA (KOA), 2 on spinal cord injury, 1 on RA, 1 on ankylosing spondylitis (AS), and 1 on osteoporosis (Tables 1 and 2).

Table 2 . Characteristics of the included animal studies

StudyModelDiseaseIntervention typeIntervention duration (wk)Modulation on microbiome
Xie et al. [15] (2020)High-fat diet-induced obese ratsKOAEA2Ratio of Bacteroidetes/Firmicutes increased.
Recovery of the relative abundance of Clostridium, Akkermansia, Butyricimonas, and Lactococcus promoted.
Zhu et al. [16] (2021)Adjuvant arthritis ratsRAMT3Relative abundance of uncategorized Clostridium, Lactobacillus, and uncategorized Prevotella decreased, whereas that of uncategorized Spironella increased.
Cheng et al. [17] (2022)SCI ratsSCIEA2Phylum Proteobacteria, class Clostridia, order Bacteroidales, and genus Dorea was reshaped.
Jia et al. [18] (2022)MIA-induced KOA ratsKOAMT2/4/6The abundances of Eubacterium coprostanoligenes and Ruminococcaceae UCG-014 increased, whereas that of the Lachnospiraceae NK4A136 decreased.
Zhang et al. [19] (2022)SCI miceSCIMT4Relative abundance of Lactobacillales and Bifidobacteriales increased, whereas that of Clostridiales decreased.
Shi et al. [20] (2021)Ovariectomized osteoporotic ratsOsteoporosisACE12The abundance of Lactobacillales (lactobacillaceae and lactobacillus), bacillales, and Streptococcus increased.

ACE, acupoint catgut embedding; EA, electroacupuncture; KOA, knee osteoarthritis; MIA, monosodium iodoacetate; MT, moxibustion; RA, rheumatoid arthritis; SCI, spinal cord injury.



4. Classification by intervention

Of the 8 studies, 3 studies used EA, 1 used acupoint catgut embedding, and 4 used moxibustion. In 2 clinical trials, EA was performed at ST35, EX-LE5, LR8, GB33 and an ashi point in KOA patients, and moxibustion was applied from DU 14 to DU 2 of governor vessel in AS patients.

5. Modulation on microbiome in human studies

In a randomized controlled trial [13] in which EA was performed on patients with KOA, Blautia, Streptococcus, and [Eubacterium]_hallii_group were significantly increased; however, Bacteroides and Agathobacter were decreased in the KOA group compared with the healthy control group. After 8 weeks of EA, the abundance of KOA-related pathogenic bacteria including [Eubacterium]_hallii_group and Streptococcus significantly decreased, and the abundance of beneficial bacteria such as Agathobacter and Lachnoclostridium significantly increased.

Another study [14] investigated the effectiveness of moxibustion on clinical outcomes and the gut microbiome modulation in patients with AS. After moxibustion, various clinical outcomes including bath AS disease activity index and bath AS function index were significantly improved in the AS patients. Furthermore, the abundances of Bacteroides and Prevotella decreased while those of Lactobacillus increased in the gut microbiome.

In recent years, the field of microbiome research is growing rapidly and is becoming a theme of great scientific interest in MSDs [21]. In this review, studies on changing the microbiome after ART in MSDs were selected and analyzed. Among MSDs, acupuncture can effectively regulate the microbiome. KOA is the most frequently studied disease, and the included studies [13,15, 18] showed that EA and moxibustion modulated the structure of the gut microbiome, including Bacteroides, Agathobacter, Clostridium, and Streptococcus. Patients with KOA have shown microbial dysbiosis compared with healthy individuals. After EA, the abundance of pathogenic bacteria including [Eubacterium]_hallii_group and Streptococcus was significantly decreased, whereas the abundance of beneficial bacteria such as Agathobacter and Lachnoclostridium was significantly increased [13]. The experimental study using KOA rats showed that microbial diversity was lower in diet-induced obesity rats (DIO-KOA) group than in control group, while 2 weeks of EA increased the microbial diversity and altered the structure of the fecal community in DIO-KOA rats. Furthermore, in the DIO-KOA group, the relative abundances of Akkermansia, Clostridium, Lactococcus, and Butyricimonas increased, whereas those of Lactobacillus, Streptococcus, Ruminococcus, Coprococcus, Roseburia, and Treponema decreased. After 2 weeks of EA in the DIO-KOA group, the relative abundance of Akkermansia, Clostridium, Lactococcus, and Butyricimonas was recovered, whereas that of Lactobacillus increased [15]. Moxibustion applied at ST35 and ST36 in monosodium iodoacetate-induced KOA rats also increased the abundances of Eubacterium coprostanoligenes group and Ruminococcaceae UCG-014, while decreased that of Lachnospiraceae NK4A136 group. Moreover, the 4-week moxibustion was more effective than the 2-week treatment [18].

In addition to KOA, this review showed the effect of ART on the microbiome modulation in various MSDs such as AS, RA and spinal cord injury. However, more studies are needed to draw definite conclusions.

Based on 8 studies published up to May 2023, ART including EA, thread-embedding acupuncture, and moxibustion could be potential treatments for regulating the microbiome in MSDs. However, given the insufficient number and quality of studies, well-designed and high- quality research is necessary.

I thank my medical student Hyeon-Jong Yoo for helping in the study selection and data extraction.

  1. Hoy DG, Smith E, Cross M, Sanchez-Riera L, Buchbinder R, Blyth FM, et al. The global burden of musculoskeletal conditions for 2010: an overview of methods. Ann Rheum Dis 2014;73:982-989. doi: 10.1136/annrheumdis-2013-204344.
    Pubmed CrossRef
  2. Sebbag E, Felten R, Sagez F, Sibilia J, Devilliers H, Arnaud L. The world-wide burden of musculoskeletal diseases: a systematic analysis of the World Health Organization Burden of Diseases Database. Ann Rheum Dis 2019;78:844-848. doi: 10.1136/annrheumdis-2019-215142.
    Pubmed CrossRef
  3. Li R, Boer CG, Oei L, Medina-Gomez C. The gut microbiome: a new frontier in musculoskeletal research. Curr Osteoporos Rep 2021;19:347-357. doi: 10.1007/s11914-021-00675-x.
    Pubmed KoreaMed CrossRef
  4. Boon E, Meehan CJ, Whidden C, Wong DH, Langille MG, Beiko RG. Interactions in the microbiome: communities of organisms and communities of genes. FEMS Microbiol Rev 2014;38:90-118. doi: 10.1111/1574-6976.12035.
    Pubmed KoreaMed CrossRef
  5. Manor O, Dai CL, Kornilov SA, Smith B, Price ND, Lovejoy JC, et al. Health and disease markers correlate with gut microbiome composition across thousands of people. Nat Commun 2020;11:5206. doi: 10.1038/s41467-020-18871-1.
    Pubmed KoreaMed CrossRef
  6. Mottawea W, Chiang CK, Mühlbauer M, Starr AE, Butcher J, Abujamel T, et al. Altered intestinal microbiota-host mitochondria crosstalk in new onset Crohn's disease. Nat Commun 2016;7:13419. doi: 10.1038/ncomms13419.
    Pubmed KoreaMed CrossRef
  7. Wilck N, Matus MG, Kearney SM, Olesen SW, Forslund K, Bartolomaeus H, et al. Salt-responsive gut commensal modulates TH17 axis and disease. Nature 2017;551:585-589. doi: 10.1038/nature24628.
    Pubmed KoreaMed CrossRef
  8. Locantore P, Del Gatto V, Gelli S, Paragliola RM, Pontecorvi A. The interplay between immune system and microbiota in osteoporosis. Mediators Inflamm 2020;2020:3686749. doi: 10.1155/2020/3686749.
    Pubmed KoreaMed CrossRef
  9. Jiang H, Deng S, Zhang J, Chen J, Li B, Zhu W, et al. Acupuncture treatment for post-stroke depression: intestinal microbiota and its role. Front Neurosci 2023;17:1146946. doi: 10.3389/fnins.2023.1146946.
    Pubmed KoreaMed CrossRef
  10. Lv Z, Liu R, Su K, Gu Y, Fang L, Fan Y, et al. Acupuncture ameliorates breast cancer-related fatigue by regulating the gut microbiota-gut-brain axis. Front Endocrinol (Lausanne) 2022;13:921119. doi: 10.3389/fendo.2022.921119.
    Pubmed KoreaMed CrossRef
  11. Yaklai K, Pattanakuhar S, Chattipakorn N, Chattipakorn SC. The role of acupuncture on the gut-brain-microbiota axis in irritable bowel syndrome. Am J Chin Med 2021;49:285-314. doi: 10.1142/S0192415X21500154.
    Pubmed CrossRef
  12. Bao C, Wu L, Wang D, Chen L, Jin X, Shi Y, et al. Acupuncture improves the symptoms, intestinal microbiota, and inflammation of patients with mild to moderate Crohn's disease: a randomized controlled trial. EClinicalMedicine 2022;45:101300. doi: 10.1016/j.eclinm.2022.101300.
    Pubmed KoreaMed CrossRef
  13. Wang TQ, Li LR, Tan CX, Yang JW, Shi GX, Wang LQ, et al. Effect of electroacupuncture on gut microbiota in participants with knee osteoarthritis. Front Cell Infect Microbiol 2021;11:597431. doi: 10.3389/fcimb.2021.597431.
    Pubmed KoreaMed CrossRef
  14. Sun G, Wang Q, Cao S, Xu H, Zhao Y. Governor vessel moxibustion therapy improves microbiota structure in ankylosing spondylitis patients. Dis Markers 2021;2021:9370758. doi: 10.1155/2021/9370758.
    Pubmed KoreaMed CrossRef
  15. Xie LL, Zhao YL, Yang J, Cheng H, Zhong ZD, Liu YR, et al. Electroacupuncture prevents osteoarthritis of high-fat diet-induced obese rats. Biomed Res Int 2020;2020:9380965. doi: 10.1155/2020/9380965.
    Pubmed KoreaMed CrossRef
  16. Zhu Y, Zhang M, Zhao C. [Effect of moxibustion at "Zusanli" (ST 36) and "Shenshu" (BL 23) on intestinal flora in adjuvant arthritis rats]. Zhongguo Zhen Jiu 2021;41:1119-1125. doi: 10.13703/j.0255-2930.20201010-k0003. Chinese.
  17. Cheng J, Li W, Wang Y, Cao Q, Ni Y, Zhang W, et al. Electroacupuncture modulates the intestinal microecology to improve intestinal motility in spinal cord injury rats. Microb Biotechnol 2022;15:862-873. doi: 10.1111/1751-7915.13968.
    Pubmed KoreaMed CrossRef
  18. Jia YJ, Li TY, Han P, Chen Y, Pan LJ, Jia CS. Effects of different courses of moxibustion treatment on intestinal flora and inflammation of a rat model of knee osteoarthritis. J Integr Med 2022;20:173-181. doi: 10.1016/j.joim.2022.01.004.
    Pubmed CrossRef
  19. Zhang Z, Sui R, Ge L, Xia D. Moxibustion exhibits therapeutic effects on spinal cord injury via modulating microbiota dysbiosis and macrophage polarization. Aging (Albany NY) 2022;14:5800-5811. doi: 10.18632/aging.204184.
    Pubmed KoreaMed CrossRef
  20. Shi N, Zhang CQ, Han L, Ouyang G. Effect of acupoint catgut embedding on intestinal flora in rats with ovariectomized osteoporosis. Acupunct Electrother Res 2021;46:307-318. doi: 10.3727/036012921X16281724938230.
    CrossRef
  21. Dunn CM, Jeffries MA. The microbiome in osteoarthritis: a narrative review of recent human and animal model literature. Curr Rheumatol Rep 2022;24:139-148. doi: 10.1007/s11926-022-01066-6.
    Pubmed CrossRef

Article

Review Article

Journal of Acupuncture Research 2023; 40(2): 129-134

Published online May 31, 2023 https://doi.org/10.13045/jar.2023.00094

Copyright © Korean Acupuncture & Moxibustion Medicine Society.

Research Trends of Acupuncture-Related Therapy on Microbiome in Musculoskeletal Disorders

Joo-Hee Kim

Department of Acupuncture and Moxibustion Medicine, College of Korean Medicine, Sangji University, Wonju, Korea

Correspondence to:Joo-Hee Kim
Department of Acupuncture and Moxibustion Medicine, College of Korean Medicine, Sangji University, 83 Sangjidae-gil, Wonju 26339, Korea
E-mail: jhkim714v@gmail.com

Received: May 9, 2023; Revised: May 11, 2023; Accepted: May 15, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

In this review, we searched for clinical and experimental studies related to acupuncture-related therapy (ART) on the microbiome in musculoskeletal disorders (MSDs) through the electronic databases of MEDLINE via PubMed, EMBASE, and Oriental Medicine Advanced Searching Integrated System up to May 2023, without language restriction, and after the selection/exclusion process, the study design, target disease, intervention details, treatment period, outcomes, and study results were extracted. A total of 8 articles were selected. Two randomized controlled trials and 6 animal studies evaluated knee osteoarthritis, rheumatoid arthritis, spinal cord injury, ankylosing spondylitis, and osteoporosis. ART, including electroacupuncture, thread-embedding acupuncture, and moxibustion, affected microbiome modulation in MSDs. The results reveal that ART could be a potential treatment for regulating the microbiome in MSDs. However, further high-quality studies are needed.

Keywords: Acupuncture, Microbiome, Musculoskeletal disorders, Research trends

INTRODUCTION

Musculoskeletal disorders (MSDs), medical conditions that can affect the muscles, bones, joints, ligaments, tendons, nerves, and other connective tissues, are one of the most common causes of physical disability and morbidity. The global burden of MSDs, including osteoarthritis (OA), rheumatoid arthritis (RA), and lower back pain, on the healthcare system and individuals has increased significantly [1,2]. MSDs are multifactorial diseases with aging and genetic and environmental components. A recent study reported that intestinal microbiota and its derived metabolites are associated with the initiation and progression of various MSDs, including osteoporosis, OA, and RA [3].

The microbiome is defined as the collection of all microorganisms and their genomes residing in a given environment including the human body [4]. With the development of next-generation sequencing technologies and advanced computational tools, accumulating evidence shows that the microbiome may play a crucial role directly or indirectly in the pathogenesis of various diseases [5]. The interaction between the host and the microbiome is disturbed in Crohn’s disease [6]. A study also reported on the interaction between high salt intake causing hypertension and the gut–immune axis and the potential role of the gut microbiome [7]. In addition, several studies have demonstrated that the gut microbiome acts on MSDs by modulating gut permeability, hormonal secretion, immune response, and so on [8].

Acupuncture, the most popular traditional Korean medicine modality, has been effectively and safely used for treating various diseases including MSDs. Some studies have shown that acupuncture not only improves clinical symptoms but also changes the intestinal microflora in various diseases, including poststroke depression [9], cancer-related fatigue [10], irritable bowel syndrome [11], and Crohn’s disease [12]. However, no review has reported the effect of acupuncture on the microbiome in MSDs.

Therefore, this study aimed to review the clinical and animal model literature related to acupuncture therapy on microbiome in MSDs and analyze the research trends for further study.

MATERIALS AND METHODS

1. Databases and search methods

A literature search was conducted using the databases of MEDLINE via PubMed, EMBASE, and Oriental Medicine Advanced Searching Integrated System (OASIS) up to May 2023. The search terms combined multiple free texts including Medical Subject Headings terms related to microbiome and acupuncture with Boolean operators. The search strategies were also adjusted for each database as appropriate. Language restriction was not implemented.

2. Inclusion and exclusion

This review included both human and animal model studies that have evaluated the effect of acupuncture on the microbiome in MSDs. In clinical literature, the study design was limited to randomized controlled trials. Interventions included all kinds of acupuncture-related therapy (ART), nonpharmacological Korean medicine treatments such as moxibustion, thread-embedding acupuncture, manual acupuncture, and electroacupuncture (EA).

Review papers were excluded; however, in the case of acupuncture review papers on the microbiome, the list of the included studies was reviewed to see if the literature on MSDs was included. Two researchers (JHK and HJY) independently performed the selection of the searched studies for eligibility. After screening the title and abstract to remove obviously irrelevant studies, the full text was examined to confirm the eligibility criteria.

3. Data extraction

Full texts of the selected studies were reviewed, and the author, publication year, study design, disease type, interventions on the treatment and control groups, and microbiome results were extracted according to a predetermined extraction form.

RESULTS

1. Study search results

A total of 490 studies were retrieved from PubMed (n = 144), EMBASE (n = 319), and OASIS (n = 27). After removing duplicates, 303 papers were reviewed after eligibility, and 8 were finally selected for review (Fig. 1).

Figure 1. Flowchart of the study selection process according to PRISMA. OASIS, Oriental Medicine Advanced Searching Integrated System; PRISMA, Preferred Reporting Items for Systematic reviews and Meta-Analyses.

2. Characteristics of the included studies

By publication year, 1 study was published in 2020, 5 in 2021, and 2 in 2022 among the 8 studies. In addition, 2 articles were human studies, and 6 were animal studies. The characteristics of the included studies and microbiome modulation results are shown in Tables 1 [13,14] and 2 [15-20].

Table 1 . Characteristics of the included human studies.

StudyStudy designDiseaseGroups (n)Intervention duration (wk)Clinical outcomesModulation on microbiome
Wang et al. [13] (2021)RCTKOAEA (30), sham EA (30), healthy (30)8WOMAC, NRS, response rateThe abundances of Bacteroides, Agathobacter increased/Streptococcus decreased.
Sun et al. [14] (2021)RCTASMT (9), healthy (9)4BASDAI, BASFI, VASThe abundances of Bacteroides, Prevotella decreased/Lactobacillus increased.

AS, ankylosing spondylitis; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; EA, electroacupuncture; KOA, knee osteoarthritis; MT, moxibustion; NRS, Numerical Rating Scale; RCT, randomized controlled trial; VAS, visual analog scale; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index..



3. Classification by disease type

Among the 8 articles included in this review that evaluated MSDs, 3 studies focused on knee OA (KOA), 2 on spinal cord injury, 1 on RA, 1 on ankylosing spondylitis (AS), and 1 on osteoporosis (Tables 1 and 2).

Table 2 . Characteristics of the included animal studies.

StudyModelDiseaseIntervention typeIntervention duration (wk)Modulation on microbiome
Xie et al. [15] (2020)High-fat diet-induced obese ratsKOAEA2Ratio of Bacteroidetes/Firmicutes increased.
Recovery of the relative abundance of Clostridium, Akkermansia, Butyricimonas, and Lactococcus promoted.
Zhu et al. [16] (2021)Adjuvant arthritis ratsRAMT3Relative abundance of uncategorized Clostridium, Lactobacillus, and uncategorized Prevotella decreased, whereas that of uncategorized Spironella increased.
Cheng et al. [17] (2022)SCI ratsSCIEA2Phylum Proteobacteria, class Clostridia, order Bacteroidales, and genus Dorea was reshaped.
Jia et al. [18] (2022)MIA-induced KOA ratsKOAMT2/4/6The abundances of Eubacterium coprostanoligenes and Ruminococcaceae UCG-014 increased, whereas that of the Lachnospiraceae NK4A136 decreased.
Zhang et al. [19] (2022)SCI miceSCIMT4Relative abundance of Lactobacillales and Bifidobacteriales increased, whereas that of Clostridiales decreased.
Shi et al. [20] (2021)Ovariectomized osteoporotic ratsOsteoporosisACE12The abundance of Lactobacillales (lactobacillaceae and lactobacillus), bacillales, and Streptococcus increased.

ACE, acupoint catgut embedding; EA, electroacupuncture; KOA, knee osteoarthritis; MIA, monosodium iodoacetate; MT, moxibustion; RA, rheumatoid arthritis; SCI, spinal cord injury..



4. Classification by intervention

Of the 8 studies, 3 studies used EA, 1 used acupoint catgut embedding, and 4 used moxibustion. In 2 clinical trials, EA was performed at ST35, EX-LE5, LR8, GB33 and an ashi point in KOA patients, and moxibustion was applied from DU 14 to DU 2 of governor vessel in AS patients.

5. Modulation on microbiome in human studies

In a randomized controlled trial [13] in which EA was performed on patients with KOA, Blautia, Streptococcus, and [Eubacterium]_hallii_group were significantly increased; however, Bacteroides and Agathobacter were decreased in the KOA group compared with the healthy control group. After 8 weeks of EA, the abundance of KOA-related pathogenic bacteria including [Eubacterium]_hallii_group and Streptococcus significantly decreased, and the abundance of beneficial bacteria such as Agathobacter and Lachnoclostridium significantly increased.

Another study [14] investigated the effectiveness of moxibustion on clinical outcomes and the gut microbiome modulation in patients with AS. After moxibustion, various clinical outcomes including bath AS disease activity index and bath AS function index were significantly improved in the AS patients. Furthermore, the abundances of Bacteroides and Prevotella decreased while those of Lactobacillus increased in the gut microbiome.

DISCUSSION

In recent years, the field of microbiome research is growing rapidly and is becoming a theme of great scientific interest in MSDs [21]. In this review, studies on changing the microbiome after ART in MSDs were selected and analyzed. Among MSDs, acupuncture can effectively regulate the microbiome. KOA is the most frequently studied disease, and the included studies [13,15, 18] showed that EA and moxibustion modulated the structure of the gut microbiome, including Bacteroides, Agathobacter, Clostridium, and Streptococcus. Patients with KOA have shown microbial dysbiosis compared with healthy individuals. After EA, the abundance of pathogenic bacteria including [Eubacterium]_hallii_group and Streptococcus was significantly decreased, whereas the abundance of beneficial bacteria such as Agathobacter and Lachnoclostridium was significantly increased [13]. The experimental study using KOA rats showed that microbial diversity was lower in diet-induced obesity rats (DIO-KOA) group than in control group, while 2 weeks of EA increased the microbial diversity and altered the structure of the fecal community in DIO-KOA rats. Furthermore, in the DIO-KOA group, the relative abundances of Akkermansia, Clostridium, Lactococcus, and Butyricimonas increased, whereas those of Lactobacillus, Streptococcus, Ruminococcus, Coprococcus, Roseburia, and Treponema decreased. After 2 weeks of EA in the DIO-KOA group, the relative abundance of Akkermansia, Clostridium, Lactococcus, and Butyricimonas was recovered, whereas that of Lactobacillus increased [15]. Moxibustion applied at ST35 and ST36 in monosodium iodoacetate-induced KOA rats also increased the abundances of Eubacterium coprostanoligenes group and Ruminococcaceae UCG-014, while decreased that of Lachnospiraceae NK4A136 group. Moreover, the 4-week moxibustion was more effective than the 2-week treatment [18].

In addition to KOA, this review showed the effect of ART on the microbiome modulation in various MSDs such as AS, RA and spinal cord injury. However, more studies are needed to draw definite conclusions.

CONCLUSION

Based on 8 studies published up to May 2023, ART including EA, thread-embedding acupuncture, and moxibustion could be potential treatments for regulating the microbiome in MSDs. However, given the insufficient number and quality of studies, well-designed and high- quality research is necessary.

ACKNOWLEDGMENTS

I thank my medical student Hyeon-Jong Yoo for helping in the study selection and data extraction.

CONFLICTS OF INTEREST

The author has no conflicts of interest to declare.

FUNDING

This research was supported by Sangji University Research Fund, 2019.

ETHICAL STATEMENT

This research did not involve any human or animal experiment.

Fig 1.

Figure 1.Flowchart of the study selection process according to PRISMA. OASIS, Oriental Medicine Advanced Searching Integrated System; PRISMA, Preferred Reporting Items for Systematic reviews and Meta-Analyses.
Journal of Acupuncture Research 2023; 40: 129-134https://doi.org/10.13045/jar.2023.00094

Table 1 . Characteristics of the included human studies.

StudyStudy designDiseaseGroups (n)Intervention duration (wk)Clinical outcomesModulation on microbiome
Wang et al. [13] (2021)RCTKOAEA (30), sham EA (30), healthy (30)8WOMAC, NRS, response rateThe abundances of Bacteroides, Agathobacter increased/Streptococcus decreased.
Sun et al. [14] (2021)RCTASMT (9), healthy (9)4BASDAI, BASFI, VASThe abundances of Bacteroides, Prevotella decreased/Lactobacillus increased.

AS, ankylosing spondylitis; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; EA, electroacupuncture; KOA, knee osteoarthritis; MT, moxibustion; NRS, Numerical Rating Scale; RCT, randomized controlled trial; VAS, visual analog scale; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index..


Table 2 . Characteristics of the included animal studies.

StudyModelDiseaseIntervention typeIntervention duration (wk)Modulation on microbiome
Xie et al. [15] (2020)High-fat diet-induced obese ratsKOAEA2Ratio of Bacteroidetes/Firmicutes increased.
Recovery of the relative abundance of Clostridium, Akkermansia, Butyricimonas, and Lactococcus promoted.
Zhu et al. [16] (2021)Adjuvant arthritis ratsRAMT3Relative abundance of uncategorized Clostridium, Lactobacillus, and uncategorized Prevotella decreased, whereas that of uncategorized Spironella increased.
Cheng et al. [17] (2022)SCI ratsSCIEA2Phylum Proteobacteria, class Clostridia, order Bacteroidales, and genus Dorea was reshaped.
Jia et al. [18] (2022)MIA-induced KOA ratsKOAMT2/4/6The abundances of Eubacterium coprostanoligenes and Ruminococcaceae UCG-014 increased, whereas that of the Lachnospiraceae NK4A136 decreased.
Zhang et al. [19] (2022)SCI miceSCIMT4Relative abundance of Lactobacillales and Bifidobacteriales increased, whereas that of Clostridiales decreased.
Shi et al. [20] (2021)Ovariectomized osteoporotic ratsOsteoporosisACE12The abundance of Lactobacillales (lactobacillaceae and lactobacillus), bacillales, and Streptococcus increased.

ACE, acupoint catgut embedding; EA, electroacupuncture; KOA, knee osteoarthritis; MIA, monosodium iodoacetate; MT, moxibustion; RA, rheumatoid arthritis; SCI, spinal cord injury..


References

  1. Hoy DG, Smith E, Cross M, Sanchez-Riera L, Buchbinder R, Blyth FM, et al. The global burden of musculoskeletal conditions for 2010: an overview of methods. Ann Rheum Dis 2014;73:982-989. doi: 10.1136/annrheumdis-2013-204344.
    Pubmed CrossRef
  2. Sebbag E, Felten R, Sagez F, Sibilia J, Devilliers H, Arnaud L. The world-wide burden of musculoskeletal diseases: a systematic analysis of the World Health Organization Burden of Diseases Database. Ann Rheum Dis 2019;78:844-848. doi: 10.1136/annrheumdis-2019-215142.
    Pubmed CrossRef
  3. Li R, Boer CG, Oei L, Medina-Gomez C. The gut microbiome: a new frontier in musculoskeletal research. Curr Osteoporos Rep 2021;19:347-357. doi: 10.1007/s11914-021-00675-x.
    Pubmed KoreaMed CrossRef
  4. Boon E, Meehan CJ, Whidden C, Wong DH, Langille MG, Beiko RG. Interactions in the microbiome: communities of organisms and communities of genes. FEMS Microbiol Rev 2014;38:90-118. doi: 10.1111/1574-6976.12035.
    Pubmed KoreaMed CrossRef
  5. Manor O, Dai CL, Kornilov SA, Smith B, Price ND, Lovejoy JC, et al. Health and disease markers correlate with gut microbiome composition across thousands of people. Nat Commun 2020;11:5206. doi: 10.1038/s41467-020-18871-1.
    Pubmed KoreaMed CrossRef
  6. Mottawea W, Chiang CK, Mühlbauer M, Starr AE, Butcher J, Abujamel T, et al. Altered intestinal microbiota-host mitochondria crosstalk in new onset Crohn's disease. Nat Commun 2016;7:13419. doi: 10.1038/ncomms13419.
    Pubmed KoreaMed CrossRef
  7. Wilck N, Matus MG, Kearney SM, Olesen SW, Forslund K, Bartolomaeus H, et al. Salt-responsive gut commensal modulates TH17 axis and disease. Nature 2017;551:585-589. doi: 10.1038/nature24628.
    Pubmed KoreaMed CrossRef
  8. Locantore P, Del Gatto V, Gelli S, Paragliola RM, Pontecorvi A. The interplay between immune system and microbiota in osteoporosis. Mediators Inflamm 2020;2020:3686749. doi: 10.1155/2020/3686749.
    Pubmed KoreaMed CrossRef
  9. Jiang H, Deng S, Zhang J, Chen J, Li B, Zhu W, et al. Acupuncture treatment for post-stroke depression: intestinal microbiota and its role. Front Neurosci 2023;17:1146946. doi: 10.3389/fnins.2023.1146946.
    Pubmed KoreaMed CrossRef
  10. Lv Z, Liu R, Su K, Gu Y, Fang L, Fan Y, et al. Acupuncture ameliorates breast cancer-related fatigue by regulating the gut microbiota-gut-brain axis. Front Endocrinol (Lausanne) 2022;13:921119. doi: 10.3389/fendo.2022.921119.
    Pubmed KoreaMed CrossRef
  11. Yaklai K, Pattanakuhar S, Chattipakorn N, Chattipakorn SC. The role of acupuncture on the gut-brain-microbiota axis in irritable bowel syndrome. Am J Chin Med 2021;49:285-314. doi: 10.1142/S0192415X21500154.
    Pubmed CrossRef
  12. Bao C, Wu L, Wang D, Chen L, Jin X, Shi Y, et al. Acupuncture improves the symptoms, intestinal microbiota, and inflammation of patients with mild to moderate Crohn's disease: a randomized controlled trial. EClinicalMedicine 2022;45:101300. doi: 10.1016/j.eclinm.2022.101300.
    Pubmed KoreaMed CrossRef
  13. Wang TQ, Li LR, Tan CX, Yang JW, Shi GX, Wang LQ, et al. Effect of electroacupuncture on gut microbiota in participants with knee osteoarthritis. Front Cell Infect Microbiol 2021;11:597431. doi: 10.3389/fcimb.2021.597431.
    Pubmed KoreaMed CrossRef
  14. Sun G, Wang Q, Cao S, Xu H, Zhao Y. Governor vessel moxibustion therapy improves microbiota structure in ankylosing spondylitis patients. Dis Markers 2021;2021:9370758. doi: 10.1155/2021/9370758.
    Pubmed KoreaMed CrossRef
  15. Xie LL, Zhao YL, Yang J, Cheng H, Zhong ZD, Liu YR, et al. Electroacupuncture prevents osteoarthritis of high-fat diet-induced obese rats. Biomed Res Int 2020;2020:9380965. doi: 10.1155/2020/9380965.
    Pubmed KoreaMed CrossRef
  16. Zhu Y, Zhang M, Zhao C. [Effect of moxibustion at "Zusanli" (ST 36) and "Shenshu" (BL 23) on intestinal flora in adjuvant arthritis rats]. Zhongguo Zhen Jiu 2021;41:1119-1125. doi: 10.13703/j.0255-2930.20201010-k0003. Chinese.
  17. Cheng J, Li W, Wang Y, Cao Q, Ni Y, Zhang W, et al. Electroacupuncture modulates the intestinal microecology to improve intestinal motility in spinal cord injury rats. Microb Biotechnol 2022;15:862-873. doi: 10.1111/1751-7915.13968.
    Pubmed KoreaMed CrossRef
  18. Jia YJ, Li TY, Han P, Chen Y, Pan LJ, Jia CS. Effects of different courses of moxibustion treatment on intestinal flora and inflammation of a rat model of knee osteoarthritis. J Integr Med 2022;20:173-181. doi: 10.1016/j.joim.2022.01.004.
    Pubmed CrossRef
  19. Zhang Z, Sui R, Ge L, Xia D. Moxibustion exhibits therapeutic effects on spinal cord injury via modulating microbiota dysbiosis and macrophage polarization. Aging (Albany NY) 2022;14:5800-5811. doi: 10.18632/aging.204184.
    Pubmed KoreaMed CrossRef
  20. Shi N, Zhang CQ, Han L, Ouyang G. Effect of acupoint catgut embedding on intestinal flora in rats with ovariectomized osteoporosis. Acupunct Electrother Res 2021;46:307-318. doi: 10.3727/036012921X16281724938230.
    CrossRef
  21. Dunn CM, Jeffries MA. The microbiome in osteoarthritis: a narrative review of recent human and animal model literature. Curr Rheumatol Rep 2022;24:139-148. doi: 10.1007/s11926-022-01066-6.
    Pubmed CrossRef
JAR
Feb 29, 2024 Vol.41 No.1, pp. 1~73

Stats or Metrics

Share this article on

  • line

Journal of Acupuncture Research

pISSN 2586-288X
eISSN 2586-2898
qr-code Download