Acupuncture improves the symptoms, intestinal microbiota, and inflammation of patients with mild to moderate Crohn's disease: A randomized controlled trial

Chunhui Bao, Luyi Wu, Di Wang, Liming Chen, Xiaoming Jin, Yin Shi, Guona Li, Jingzhi Zhang, Xiaoqing Zeng, Jianhua Chen, Huirong Liu, Huangan Wu, Chunhui Bao, Luyi Wu, Di Wang, Liming Chen, Xiaoming Jin, Yin Shi, Guona Li, Jingzhi Zhang, Xiaoqing Zeng, Jianhua Chen, Huirong Liu, Huangan Wu

Abstract

Background: The efficacy and mechanisms of acupuncture for Crohn's disease (CD) are not well understood. We investigated its effects on symptoms, intestinal microbiota, and circulating inflammatory markers in CD patients.

Methods: This 48-week, randomized, sham controlled, parallel-group clinical trial was performed at a tertiary outpatient clinic in China. From April 2015 to November 2019, 66 patients (mean age 40·4, 62·1% were male, all were Han Chinese) with mild to moderate active CD and unresponsive to drug treatment were enrolled and randomly assigned equally to an acupuncture group or a sham group. The treatment group received 3 sessions of acupuncture plus moxibustion per week for 12 weeks and a follow-up of 36 weeks. Clinicaltrials.gov: NCT02559037.

Findings: At week 12, the clinical remission rate (the primary outcome) and clinical response rate of acupuncture group were significantly higher than that of sham group, with a difference of 42·4% (95% CI: 20·1%-64·0%) and 45·5% (95% CI: 24·0%-66·9%), respectively, both of which maintained at week 48. The acupuncture group had significantly lower CD activity index and C-reactive protein level at week 12, which maintained at 36-week follow-up. The CD endoscopic index of severity, histopathological score, and recurrence rate at week 48 were significantly lower in acupuncture group. The number of operational taxonomic unit of intestinal microbiota and relative abundance of Faecalibacterium prausnitzii and Roseburia faecis were increased. Plasma diamine oxidase, lipopolysaccharide, and Th1/Th17 related cytokines were decreased in 12-week after acupuncture.

Interpretation: Acupuncture was effective in inducing and maintaining remission in patients with active CD, which was associated with increased abundance of intestinal anti-inflammatory bacteria, enhanced intestinal barrier, and regulation of circulating Th1/Th17-related cytokines.

Funding: National Key Basic Research Program of China (2015CB554500 and 2009CB522900), Shanghai Rising-Star Program (19QA1408100).

Keywords: Acupuncture; Alternative therapy; CD, Crohn's disease; CDAI, Crohn's disease activity index; CDEIS, Crohn's disease endoscopic index of severity; CRP, C-reactive protein; DAO, diamine oxidase; Gut microbes; HCs, healthy control subjects; HS, histopathological score; IBD, inflammatory bowel disease; ITT, intention to treat; Inflammatory bowel disease; Intestinal barrier; LEfSe, linear discriminant analysis effect size; LPS, lipopolysaccharides; OTU, operational taxonomic unit; PP, per-protocol; SCFAs, short chain fatty acids.

Conflict of interest statement

All the authors disclose no conflicts of interest.

© 2022 The Author(s).

Figures

Figure 1
Figure 1
The CONSORT flowchart of the patient flow throughout the study.
Figure 2
Figure 2
Acupuncture treatment significantly increased the rate of CD remission in 12 weeks after treatment, ITT analysis (n = 33 in each group) and PP analysis (n = 32 in acupuncture group, n = 31 in sham group). Proportion of patients with clinical remission (CDAI score <150 and decrease ≥70 from baseline) at the completion of 12-week treatment.
Figure 3
Figure 3
Acupuncture treatment had a better effect on clinical remission and clinical response to CD, as well as on decreasing the CDAI score and CRP level at week 12 and 36-week follow-up (n = 33 in each group). Proportion of patients with (a) clinical remission (CDAI score < 150 and decreased ≥ 70 from baseline) and (b) Clinical response (decrease in CDAI score by ≥ 70 from baseline) at weeks 12, 24, 36, and 48 for ITT analysis. The mean change in (c) CDAI score and (d) CRP level from baseline at weeks 12, 24, 36, and 48 for ITT analysis.
Figure 4
Figure 4
Acupuncture treatment significantly decreased CDEIS score and HS at the end of 48-week follow-up (n = 10 in each group). (a) CDEIS score at baseline and week 48; (b) Mean change in CDEIS score from baseline at week 48; (c) HS at baseline and week 48; (d) Mean change in HS from baseline at week 48.
Figure 5
Figure 5
(a) Cladogram of the linear discriminant analysis (LDA) effect size (Lefse) analysis of significant difference of microbial population. (b) Histogram of the LDA score of microbes that showed a significant impact in the acupuncture group (n = 15), sham group (n = 15) at the end of treatment and HCs (n = 30).

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Source: PubMed

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