Rheumatology · Medical Literature
[Clinical study on efficacy and mechanism of separated moxibustion in the treatment of rheumatoid arthritis and related negative emotions based on gut microbiota].
Abstract
To investigate the clinical efficacy of separated moxibustion in the treatment of rheumatoid arthritis (RA) and related negative emotions based on gut microbiota, so as to explore its potential mechanism of action. A total of 70 RA patients were randomly divided into a control group (n=35, 2 cases dropped off, 3 cases were excluded) and an observation group (n=35, 3 cases dropped off, 2 cases were excluded), and 30 healthy participants who underwent physical examination during the same period were randomly enrolled as the normal group. The control group was given conventional drug therapy;the observation group was additionally treated with separated moxibustion at bilateral Zusanli (ST36), Shenshu (BL23) and Ashi points on the basis of the control group, once every other day, 3 times a week, for 5 consecutive weeks. The scores of disease activity score in 28 joints (DAS28), visual analogue scale (VAS) for pain, morning stiffness, gastrointestinal symptom rating scale (GSRS), self-rating anxiety scale (SAS), and self-rating depression scale (SDS) were compared between the control group and observation group before and after treatment. 16S ribosomal RNA (rRNA) gene sequencing was used to detect the composition structure and relative abundance of gut microbiota in the 3 groups before and after treatment. ELISA was adopted to measure the serum contents of lipopolysaccharide (LPS), lipopolysaccharide-binding protein (LBP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), 5-hydroxytryptamine (5-HT), and insulin-like growth factor-1 (IGF-1) in the control and observation groups before and after treatment. Compared with the baseline in the same group, the scores of DAS28, VAS, GSRS, SAS, SDS, as well as serum contents of LPS, LBP, TNF-α, IL-1β and IL-6 were significantly decreased in both the control and observation groups after treatment (P<0.05, P<0.01), and the reductions in the observation group were more significant than those in the control group (P<0.05, P<0.01). In contrast, morning stiffness score was significantly decreased, and serum contents of 5-HT and IGF-1 were significantly increased in the observation group after treatment compared with baseline and those in the control group after treatment (P<0.05, P<0.01). Before treatment, compared with the normal group at the same time point, the α -diversity of gut microbiota (Chao1, Ace, Sobs, Shannon indices) and the abundances of beneficial bacteria (Bacteroidota, Faecalibacterium, Bacteroides, Bifidobacterium) in the observation and control groups were significantly lower (P<0.01), while the Firmicutes/Bacteroidota (F/B) ratio and the abundances of opportunistic pathogenic bacteria (Firmicutes, Prevotella, Proteobacteria, Actinobacteriota, Escherichia-Shigella, Klebsiella) were significantly higher (P<0.01). Microbiota clustering analysis showed significant differences between the observation/control groups and the normal group. After treatment, all the above indicators were improved in observation/control groups, and the observation group showed significantly better outcomes in increasing α -diversity, restoring beneficial bacteria abundance, and reducing F/B ratio and pathogenic bacteria abundance than the control group (P<0.01, P<0.05). Separated moxibustion combined with conventional drugs exerts superior clinical efficacy to monotherapy with conventional drugs in relieving joint pain, improving gastrointestinal symptoms, and alleviating anxiety and depression in RA patients. Its mechanism may be associated with regulating gut microbiota diversity, optimizing microbiota structure, reducing inflammatory factor levels, and improving neurotransmitter metabolism.
Clinical relevance
This RCT addresses the underexplored gut-joint-brain axis in rheumatoid arthritis (RA), a population in whom gastrointestinal dysbiosis, systemic inflammation, and neuropsychiatric comorbidities (anxiety, depression) frequently coexist and remain inadequately managed by conventional DMARDs/biologics alone. By integrating separated moxibustion (a traditional Chinese medicine intervention) with standard pharmacotherapy, it offers a mechanistically grounded adjunctive strategy targeting gut microbiota modulation and neuroimmune pathways. Clinicians managing refractory RA symptoms—particularly gastrointestinal burden, morning stiffness, and mood disorders—should be aware of this emerging multimodal approach.
Key findings
1. Disease activity (DAS28 scores) and pain (VAS scores) were significantly reduced in both the observation (moxibustion + conventional drugs) and control (conventional drugs alone) groups post-treatment (P<0.05 to P<0.01), with significantly greater reductions observed in the observation group (P<0.05 to P<0.01); specific effect sizes and CIs were not reported in the abstract. 2. Morning stiffness scores were significantly decreased only in the observation group after treatment versus both baseline and the control group post-treatment (P<0.05 to P<0.01), suggesting moxibustion provides incremental benefit beyond pharmacotherapy for this outcome. 3. Gastrointestinal symptom burden (GSRS scores) and neuropsychiatric comorbidity (SAS and SDS scores for anxiety and depression) were significantly reduced in both groups, with the observation group demonstrating significantly superior improvements (P<0.05 to P<0.01); absolute score differences were not provided. 4. Pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and gut permeability/endotoxemia markers (LPS, LBP) were significantly decreased in both groups post-treatment, with significantly greater reductions in the observation group (P<0.05 to P<0.01), supporting an anti-inflammatory and barrier-restorative mechanism. 5. Serum 5-hydroxytryptamine (5-HT) and insulin-like growth factor-1 (IGF-1) were significantly elevated only in the observation group after treatment compared with both baseline and the control group (P<0.05 to P<0.01), implicating neurotransmitter and anabolic pathway modulation as moxibustion-specific effects. 6. At baseline, RA patients in both treatment groups exhibited significantly reduced gut microbiota α-diversity (Chao1, ACE, Sobs, Shannon indices) and lower abundance of beneficial taxa (Bacteroidota, Faecalibacterium, Bacteroides, Bifidobacterium), alongside a significantly elevated Firmicutes/Bacteroidota (F/B) ratio and enrichment of opportunistic pathogens (Firmicutes, Prevotella, Proteobacteria, Actinobacteriota, Escherichia-Shigella, Klebsiella) versus healthy controls (P<0.01); after treatment, the observation group showed significantly greater restoration of α-diversity, beneficial bacteria abundance, and reduction in F/B ratio and pathogen abundance than the control group (P<0.01 to P<0.05).
Practice implications
For RA patients with concurrent gastrointestinal symptoms, morning stiffness refractory to pharmacotherapy alone, or comorbid anxiety/depression, adjunctive separated moxibustion at bilateral ST36 (Zusanli), BL23 (Shenshu), and Ashi points—administered every other day, three times weekly for five consecutive weeks—may be considered as part of an integrative treatment plan alongside conventional drug therapy. Clinicians should monitor not only standard RA disease activity indices (DAS28, VAS, morning stiffness) but also gastrointestinal symptom burden and mood scales (GSRS, SAS, SDS), as moxibustion appears to confer benefits across these domains via gut microbiota modulation and neuroimmune mechanisms. Given the modest sample size (30 evaluable patients per arm), absence of reported confidence intervals and NNT, and single-center design, these findings should be interpreted as hypothesis-generating; larger multicenter RCTs with standardized microbiome profiling and blinded outcome assessment are needed before routine clinical adoption.