Efficacy and MicroRNA-Gut Microbiota Regulatory Mechanisms of Acupuncture for Severe Chronic Constipation: Study Protocol for a Randomized Controlled Trial

Abstract

BackgroundSevere chronic constipation (SCC) is a common functional gastrointestinal (GI) disorder associated with disruptions in GI motility. Abnormalities between gut microbiota and microRNAs (miRNAs) are implicated in the pathogenesis of GI motility in SCC. Acupuncture has been shown to improve constipation-related symptoms and rebalance the gut microbiota. This protocol proposed a plan to explore the hypothesis that the efficacy of acupuncture is associated with the crosstalk between gut microbes and miRNAs in patients with SCC.MethodsThis trial is designed as a randomized, sham-controlled trial involving 80 patients and 40 healthy volunteers. A total of 80 patients with SCC (≤2 mean spontaneous, complete bowel movements per week [CSBMs]) will be randomly allocated to receive either 16-session acupuncture at true acupoints or non-penetrating sham acupuncture at non-acupoints for 4 weeks. The primary outcome will be the proportion of patients with ≥3 mean weekly CSBMs over weeks 1–4 and 5–8. Secondary efficacy endpoints include bowel movements, stool consistency, degree of straining, and the quality of life. Healthy volunteers will not receive any clinical intervention. Fasting plasma and fecal samples will be analyzed by 16S rRNA third-generation sequencing and miRNA high-throughput sequencing technologies. Finally, a tripartite network analysis will be used to investigate the interactions among clinical efficacy, miRNAs, and intestinal microbiota.DiscussionFrom the perspective of microRNA-gut microbiota regulatory mechanisms, our results will partially illuminate the crucial role of fecal miRNAs and intestinal microbiota to understand how acupuncture exerts its anti-constipation role.Trial registrationThis trial is registered with ChiCTR2100048831, registered 18 July 2021; ethical approval has been obtained from the Sichuan Regional Ethics Review of Committee on Traditional Chinese Medicine, approval ID: 2021KL-023.

The gut microbiome and metabolites are altered and interrelated in patients with functional constipation

“…Currently, laxatives are a favorable choice for alleviating relative symptoms of FC (Liu et al, 2016 ). However, frequent usage of laxatives can result in drug dependence and a cathartic colon; therefore, a laxative is not a satisfactory therapy for FC patients (Yao et al, 2022 ). Therefore, there is a perceived need to perform further research into the mechanism of FC, with the aim of enhancing the efficacy of treatment strategies.…”

Clinical observation and mechanism of acupuncture on amnestic mild cognitive impairment based on the gut-brain axis: study protocol for a randomized controlled trial

“…Recently, increasing number of randomized clinical trial (36,60,61) have recruited healthy volunteers and determined the pathological features in the population of patients by comparing them with patients. Patients with MCI were reported to have altered levels of peripheral and cerebrospinal fluid inflammatory markers, abnormal cognitive-related brain network function, and distinct gut microbiota composition compared with healthy controls (62)(63)(64).…”

Effects of acupuncture on gut microbiota and short-chain fatty acids in patients with functional constipation: a randomized placebo-controlled trial

“…It is well established that the primary physiopathologic mechanism of FC is decreased intestinal motility associated with reduced sensitivity of both sympathetic and parasympathetic nervous systems. Previous studies have demonstrated that acupuncture at acupoints ST25, ST37, and SP14 can effectively increase bowel movements (Liu et al, 2016;Yao et al, 2022b). It has been described that the deep sections of ST25 and SP14 correspond to the nerve segments of the large intestine (T10) and the small intestine (T11), respecitevely, which exert bidirectional influence on peristalsis and contraction via sympathetic or parasympathetic nerves (Yu et al, 2016;Zeng and Chen, 2022).…”