Irritable bowel syndrome (IBS), a common functional gastrointestinal disorder, is characterized by recurrent abdominal pain or abdominal discomfort (the latter has been removed from the Rome IV criteria) and abnormal bowel habits [
Currently, no generally accepted therapies are available to halt the progression of IBS, even though tremendous efforts have been made to uncover the mechanism of IBS. Besides, conventional pharmacotherapies (CP), such as antispasmodics, antidiarrheal agents, antidepressants, 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, probiotics, and antibiotics, cannot achieve satisfactory clinical efficacy, and some of them are even associated with the risk of incidence of cardiovascular events and ischemic colitis [
Therefore, an increasing number of IBS patients have turned to alternative medicine, especially for traditional Chinese medicine (TCM), for symptom alleviation. Chinese herbal medicine (CHM) and acupuncture have long been practiced for a history of over two thousand years, which are recognized to be the most effective and popular therapies based on holistic concepts and syndrome differentiation of the TCM system. Some previous reviews regarding CHM [
Relevant RCTs were systemically retrieved from the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Biological Medical Database (CBM, SinoMed), China Science and Technology Journal Database (VIP), and Wan Fang Data, from their inception to March 2018 using the search terms of “irritable bowel syndrome,” “IBS,” “irritable colon,” “colon spasm,” “allergic colitis,” “colon allergy,” “irritable colon syndrome,” “acupuncture,” “acupuncture therapy,” “electroacupuncture,” “acupressure,” “ warm acupuncture,” “needling,” “needle warming moxibustion,” “auriculotherapy,” “traditional Chinese medicine,” “Chinese herbal medicine,” “herbal medicine,” “Chinese medicine,” and “complementary and alternative medicine.”
Afterwards, the full-texts of all the eligible studies identified were reviewed, and study data were extracted by two researchers independently using a unified form. The original authors would be contacted for further information when the outcome data of relevant studies were unclear or missing. Any disagreement was resolved after discussion with the third author. Typically, the study inclusion criteria of this meta-analysis were as follows: (1) studies that employed clear diagnostic criteria of IBS-D, such as the Rome I–IV criteria; (2) randomized controlled trials; (3) studies in which participants in experimental group had received acupuncture (including electroacupuncture, needling, acupressure, auriculotherapy, or needle-warming moxibustion) combined with CHM (such as decoction, granules, capsule, pill, tablet, powder, or injection), while subjects in control group underwent unlimited treatment types (such as western medicine, western medicine combined with CHM, Chinese medicine alone, or acupuncture alone); and (4) studies published in Chinese or English language. Meanwhile, the study exclusion criteria were as follows: (1) studies focusing on IBS-C, IBS-M, or IBS-U; (2) duplicate publications; (3) studies enrolling participants with severe enteric disease or who developed heart failure, renal failure, or a malignancy during the study period; (4) commentary, editorial, experience introduction, conference article, review, graduation thesis, or case report; (5) nonhuman or animal studies; (6) studies in which there were intervention measures in treatment group other than acupuncture and CHM; (7) the articles had no clear outcome indexes, or incomplete data; and (8) studies whose conclusions had conflicted with the original data.
Data were extracted and assessed by two reviewers independently based on a unified form, and any disagreement was settled through discussion with a third reviewer. The extracted study data included first author, year of publication, criteria of western medicine and TCM, study population, age, number of participants in experimental and control groups, interventions, outcomes, follow-up, and duration. Moreover, the methodological quality was evaluated by two authors independently based on the Cochrane Collaboration’s risk of bias tool [
The Review Manager 5.3 and Stata12.0 softwares were applied in this meta-analysis. In addition, the pooled relative risk (RR) and 95% confidence interval (CI) were reported for the clinical efficacy rate, while standardized mean difference (SMD) and 95% CI were reported for the continuous variable data. The potential heterogeneity was assessed by chi-square test and the inconsistency index statistic (I2), respectively [
A total of 648 studies were identified from the electronic bibliographic databases, among which 197 duplicate studies were removed. After reviewing the titles and abstracts, 384 studies were excluded since they were not qualified according to the predefined inclusion criteria. Then, the full-texts of the remaining articles were read, and 46 studies were excluded owing to non-RCTs (n = 11), including IBS-C or IBS-M subtypes (n = 10), incorrect criteria (n = 1), lack of relevant intervention treatment (n = 4), repeated published data (n = 4) and unreliable data (n = 16) including inconsistent data (the statistical results by the authors are inconsistent with the data in the literature, n = 10; average value of symptoms obtained in the results conflicted with the scoring criteria, n = 4; and the number of participants was inconsistent, n = 1), and incomplete data (the scoring criteria and symptom scores were not presented, n = 1). Eventually, 21 eligible studies were included into this systematic review and meta-analysis. Figure
Flow chart of the process for literature retrieval.
The study characteristics are presented in Tables
Characteristics of included literature.
Source | Criteria | Study population | Age (years) | N | Intervention | Outcomes | Follow-up | Side effects | |||
---|---|---|---|---|---|---|---|---|---|---|---|
Western | TCM | EG | CG | EG | CG | ||||||
Shi ZM | RomeII | N.M | Single center | 20-55 | 22-58 | 30/30 | Modified Sini Decoction and TXYF + Acupuncture | OT+DT+BT+MP | A | N.M | N.M |
Hu FL | RomeII | N.M | Single center | 22-68, mean:37 | 20-60, mean:35 | 37/32 | Modified TXYF+ Acupuncture | CGEC+MP+OT | A | N.M | N.M |
Zhang SY 2006 | RomeII | LQSASDS | Single center | N.M | N.M | 40/25 | Oral: Modified Chaishao Yigong and Xiangsha Pingwei Decoction, Enema: Self-ordained TCM Decoction + Acupuncture | LHS+MP | A | N.M | N.M |
Yu YG | RomeI | N.M | Single center | 44 | 43 | 32/28 | Chang Ling capsule + acupuncture | TDC | A | N.M | N.M |
Lan YP | RomeII | LQSASDS | Single center | 18-62 | 19-61 | 40/40 | Modified TXYF+ Acupuncture | MP+OT | A+O | 6 months | N.M |
Cao S | RomeII | N.M | Single center | N.M | N.M | 70/70 | HXZQ Pill, or HXZQ Capsule, or HXZQ oral liquid | RP+MBND | A | N.M | N.M |
Tang JL | Rome III | N.M | Two | N.M | N.M | N.M | Jianpi Huazhuo Tongluo Decoction + Acupuncture | LBP | C+D+F+H+K+M+N+S | N.M | N.M |
Jiang QY | Rome III | LSAASS | Single center | 39.56±11.32 | 37.48±13.79 | 52/54 | Chaihu Shugan Decoction + Acupuncture | OBT | A | N.M | T: 2 cases, |
Jin J | Rome III | N.M | Single center | 42.52±3.73 | 42.94±3.81 | 52/52 | Modified TXYF+ Acupuncture | RP, MBND | A+ T | N.M | T: 2 cases, |
Zhou P | Rome III | LQSASDS | Single center | 16~64, | 17~65, | 45/45 | Modified XYS+ Acupuncture | MP+CGEC+CAECT | A+D+F+L+N+U | 12 weeks | N.M |
Yan YZ | Rome III | LQSASDS | Single center | 38.25 | 36.75 | 52/50 | Modified TXYF+ Acupuncture | PBT+CBLEABCT | A | N.M | C: 3 cases |
Xu SC | Rome III | LQSASDS | Single center | 42.3 | 40.9 | 30/30 | Modified TXYF+ Acupuncture | PBT | A | N.M | N.M |
Li YX | N.M | N.M | Single center | 41.1±7.87 | 40.2±8.56 | 50/48 | Modified XYS + Acupuncture | MP+CGEC | A+C+F+L+N | 12 weeks | no |
Sun W | Rome III | MBND | Single center | 31.5±7.4 | 32.8±8.1 | 60/60 | Jianpi Huazhuo Tongluo Decoction + Acupuncture | PBT | A | N.M | N.M |
Zhi YC | Rome III | LQSASDS | Single center | 42.4±7.4 | 41.8±7.3 | 30/30 | Dunhuang Baoyuan Decoction + Acupuncture | PBT | A | N.M | C: 1case |
Wang XH 2016 | Rome III | CCSS | Single center | 38.93±5.98 | 39.40±7.94 | 30/30 | BXXX Decoction + Acupuncture | PBT | A+B | N.M | N.M |
Chen S | Rome III | N.M | Single center | 38.21±10.65 | 40.07±9.38 | 60/59 | Shugan Jianpi Zhixie Decoction + Acupuncture | PBT | A+B | N.M | N.M |
Yang JY | Rome III | N.M | Single center | 48.20±4.59 | 47.49±5.23 | 35/35 | Modified SLBZS+ Acupuncture | TMT | A+P+Q+R | 4 weeks | C: 5cases |
Hou GH | Rome III | LSAASS or WOSASS | Single center | 36.75 | 37.55 | 52/52 | CGECC+ Acupuncture | SB+PBT | A+C+D/E+F | N.M | C: 2 cases |
Wang W | Rome III | DBLASS | Single center | 35.2±4.3 | 36.2±5.0 | 102/105 | Self-ordained TCM Decoction + Acupuncture | PBT | A+B+C+D+G+L+M | N.M | C: 3 cases |
Sun M | Rome III | MBND | Single center | 38.79±5.89 | 38.65±5.76 | 30/30 | BXXX Decoction + Acupuncture | PBT | A+B | N.M | N.M |
Annotation:
EG: experiment group; CG: control group; N.M: not mentioned; MBND: mentioned but not described;
CCS: cold-heat complicated syndrome; DBLASS: disharmony between liver and spleen syndrome; LQSASDS: Liver qi stagnation and spleen deficiency syndrome; LSAASS: Liver-qi stagnation and attacking spleen syndrome; WOSASS: weakness of spleen and stomach syndrome;
A: clinical therapeutic efficacy; B: TCM symptom therapeutic effect; C: abdominal pain score; D: abdominal distention score; E: abdominal discomfort score; F: diarrhea score; G: frequency of defecation score; H: mucous stool score; I: borborygmus score; J: property of stool score; K: tenesmus; L: diet condition score; M: sleeping quality score; N: physical strength; O: recurrence rate; P: IBS-QOL score; Q: IBS-BSS score; R: SCL 90; S: SF-36 scale; T: the level of serum inflammatory factor; U: the score of Hamilton Depression Rating Scale
BT: belladonna tablets; BXXX: Banxia Xiexin; CBLEABCT: combined bifidobacterium lactobacillus enterococcus and bacillus cereus tablets (Live); CGECC: compound glutamine enteric-coated capsules; DT: diazepam tablets; HXZQ: Huoxiang Zhengqi; LBP: live bifidobacterium preparation; LHS: loperamide hydrochloride capsules; MP: montmorillonite powder; OBT: otilonium bromide tablets; OT: oryzanol tablets; PBT: pinaverium bromide tablets; SB: saccharomyces boulardii sachets; SLBZS: Shenling Baizhu San; TMT: trimebutine maleate tablets; TXYF: Tongxie Yaofang; XYS: Xiayao San.
In terms of the dosage form in experimental group, 18 studies had used decoction [
With regard to acupuncture, 13 trials had used conventional acupuncture alone [
In this meta-analysis, the primary outcome was the clinical efficacy rate, while the secondary outcomes were TCM symptom scores of abdominal pain, abdominal distension or discomfort, diarrhea, diet condition, physical strength, and sleep quality. Besides, adverse reactions and long-term efficacy were also recorded in this meta-analysis.
Further information about some of the included trials was requested from the authors by e-mail; unfortunately, no response was received. Typically, ten RCTs had adopted a random number table to divide the participants into experimental group [
(a) Risk of bias summary. (b) Risk of bias graph.
A total of 20 RCTs had reported the clinical efficacy rate [
Our results indicated that acupuncture combined with CHM could enhance the clinical effectiveness compared with the control group treated with western medicine alone or western medicine combined with CHM (RR 1.29, 95% CI 1.24–1.35, P < 0.00001); however, mild heterogeneity was discovered (
Forest plot of clinical therapeutic efficacy.
The metaregression analysis was performed with the name of prescriptions, acupuncture type, treatment course, and publication year as independent variables; the results indicated that the heterogeneity could not be well explained (Table
Results of metaregression analysis.
Variable | Coefficient | Standard Error | t | P | 95% CI |
---|---|---|---|---|---|
Prescription type | -0.007347 | 0.0163976 | -0.45 | 0.661 | 0.0422977, 0.0276037 |
Acupuncture type | 0.0071692 | 0.0404282 | 0.18 | 0.862 | -0.0790014, 0.0933399 |
Treatment course | -0.0648648 | 0.0767705 | -0.84 | 0.411 | -0.2284971, 0.0987676 |
Publication year | -0.0909341 | 0.072595 | -1.25 | 0.230 | -0.2456667, 0.0637986 |
Subgroup analysis stratified based on the name of prescriptions was further conducted to identify the underlying source of heterogeneity, including Tongxie Yaofang (TXYF), Xiaoyao San (XYS), Banxia Xiexin (BXXX) decoction, and Shenling Baizhu San (SLBZS) that were derived from ancient time, as well as other CHM containing the self-ordained TCM decoctions and Chinese patent medicines formed in modern time. Compared with the control groups, the experimental groups had displayed favorable effects on boosting the clinical efficacy rate for the modified TXYF combined with acupuncture (RR 1.30, 95% CI 1.21–1.40, P < 0.00001) in eight trials with no heterogeneity (
Five out of the included trials had evaluated the improvement of abdominal pain based on the symptom scores [
Forest plot of improvement in abdominal pain.
Three studies had assessed the abdominal distention score [
Forest plot of improvement in abdominal distention or discomfort score.
Four out of the included studies had evaluated the diarrhea score [
Forest plot of improvement in diarrhea score.
Three of the 21 studies had mentioned the outcome of diet improvement [
Forest plot of improvement in the diet condition score.
Three out of the included trials had discussed the outcome of physical strength [
Forest plot of improvement in physical strength score.
Two of the enrolled articles had assessed the sleep quality [
Forest plot of improvement in sleeping quality score.
A total of eight enrolled studies had evaluated the safety profile [
Among all enrolled studies, two trials had evaluated the long-term curative effect [
Figure
Funnel plot of publication bias.
Altogether 21 RCTs related to IBS-D were included into the current meta-analysis, and the pooled results demonstrated that (1) acupuncture combined with CHM had exhibited favorable improvement compared with the controls; (2) compared with the matched groups treated with western medicine or western medicine combined with CHM, the combined method could markedly enhance the clinical therapeutic efficacy in the meantime of reducing the scores for abdominal pain, abdominal distention/discomfort, diarrhea, diet condition, physical strength, and sleep quality; (3) IBS-D patients treated with the combined method would not suffer from obvious adverse events and promising long-term efficacy could be attained by the combined method; and (4) the low methodological quality of the enrolled articles would give rise to evidence of publication bias, which should be further improved in future studies.
IBS is a common disease, but no universally accepted therapy is available at present to halt its progression. Hence, increasing patients and practitioners have turned to acupuncture combined with CHM for treatment. Typically, acupuncture contributes to achieving obvious and fast effect without causing adverse reaction; however, it is limited by its action area and span. As is well known, CHM has comprehensive and long-lasting effects, but some medicine-related side effects have been reported [
In addition, the therapeutic schedules were different among the 21 included trials, and the most appropriate combination of acupuncture and CHM could be formulated through systemic analysis to achieve better therapeutic results. In acupuncture, traditional Chinese physicians prefer to apply needles without using electroacupuncture apparatus. Typically, the top six most commonly used acupoints were Zusanli (ST36), Tianshu (ST25), Taichong (LR3), Sanyinjiao (SP6), Shangjuxu (ST37), and Zhongwan (RN12), which had played an important and synthesized role in invigorating the spleen, resisting diarrhea, relieving the liver, and alleviating pain. Additionally, the most commonly adopted meridians were the Stomach Meridian of Foot-Yangming, the Liver Meridian of Foot-Jueyin, the Spleen Meridian of Foot-Taiyin, the Ren Meridin, and the Bladder Meridian of Foot-Taiyang. Typically, acupoints were mainly selected based on Zang Fu organs and meridians, which were often joined in the following ways, he-sea point matching front Mu point, back-shu point matching front Mu point, and back-shu point matching he-sea point; for instance, Zusanli (ST36) and Zhongwan (RN12), Pishu (BL20) and Tian shu (ST25), or Pishu (BL20) and Zusanli (ST36).
In the field of CHM, 18 among the enrolled RCTs had applied a Chinese herbal decoction [
More importantly, this was the first systematic review and meta-analysis to assess the efficacy of acupuncture combined with CHM in treating IBS-D, which was also the first to assess the scores for diet condition, physical strength, and sleep quality compared with other meta-analyses evaluating the effect of CHM or acupuncture on IBS-D [
Acupuncture combined with CHM can achieve a satisfactory synergistic effect, which may be ascribed to the following aspects [
Yuan et al. had demonstrated that TXYF could inhibit the colonic hypermotility through preventing the influx of extracellular Ca2+ into the isolated rat colonic smooth muscle cells [
Besides, other studies have also uncovered the mechanism of action of acupuncture in treating IBS-D, and experimental data show that electroacupuncture at Zusanli can also inhibit the vimentin protein expression level to adjust the gastrointestinal motility [
The current meta-analysis was inevitably associated with some limitations, as displayed below.
(1) Geographical distribution: the combined method required that clinicians should master acupuncture and prescribe the Chinese medicine prescriptions expertly, which would inevitably lead to a geographically limited distribution of studies; therefore, the studies included in this meta-analysis were all conducted in China and published in the Chinese language.
(2) Poor methodological quality: only ten of the enrolled studies had employed a random number table for participant grouping [
(3) Evident heterogeneity: although the intervention and control groups were strictly incorporated into this meta-analysis, there was still moderate or high heterogeneity. Consequently, metaregression and subgroup analyses were performed to search for the potential source of heterogeneity. For metaregression analysis, it could not well explain heterogeneity. Instead, for subgroup analyses, with regard to clinical efficacy rate, the study by Yang et al. might account for one main source of significant heterogeneity [
(4) Potential evidence of publication bias: a majority of the enrolled studies in this meta-analysis had a small sample size and had reported a negative result, which might account for the major source of publication bias.
(5) Short-term interventions and follow-up: the treatment duration in most of the included studies was 4 weeks, and only four studies had mentioned follow-up [
To the best of our knowledge, this is the first systematic review and meta-analysis of acupuncture combined with CHM in treating IBS-D. The results indicate that the combined method is suggestive of an effective and safe therapy, which may serve as a promising method to treat IBS-D in practical application. However, the included studies of this meta-analysis are associated with poor methodological quality and heterogeneity in diagnostic and evaluation criteria, as well as in interventions of acupuncture and CHM; consequently, further rigorously designed, multicenter, and large-scale clinical RCTs are required to overcome the limitations of the current study and to enhance the strength of evidence.
There are no conflicts of interest.
Jing Yan, Zhi-wei Miao, Li-na Liu, and Zhi-guang Sun contributed to conceiving and designing the experiments; Jing Yan, Zhi-wei Miao, Jun Lu, Li-hua Yu, and Fei Ge had performed the experiments; Jing Yan, Zhi-wei Miao, and Jun Lu had analyzed the data; Wen-bin Shang, Li-hua Yu, and Fei Ge had made contributions to the reagents/materials/analysis tools; Jing Yan and Li-na Liu had contributed to manuscript compiling; and Li-na Liu and Zhi-guang Sun was responsible for study supervision. Jing Yan and Zhi-wei Miao contributed equally to this work.
This research was supported by the National Natural Science Foundation of China, Nos. 81503536, 81603578, and 81673795; the Natural Science Foundation of Jiangsu Province, Nos. BK20151008, BK20140959, BK20151567, and BK20181235; the Jiangsu Provincial Bureau of Traditional Chinese Medicine, YB2017066; and the Nanjing Science and Technology Development Plan Project, 201715072.
S1 File: a sample retrieval strategy.
S1 Table: details of acupuncture in the included trials.
S2 Table: details of CHM in the included trials.
S2 File: tests for Publication Bias.
S3 File: PRISMA checklist.