Effect of Resistant Starch on Symptom Improvement and Intestinal Microbiome in Patients With Functional Constipation
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Changes in the relative abundance of species of intestinal flora
研究概览
简要总结
Constipation is one of the most common gastrointestinal (GI) disorders in clinical practice, with approximately 11-20% of adults worldwide suffering from constipation. Clinically, the frequency of defecation is reduced, or the defecation is laborious, obstructed, difficult, and the stool is dry and difficult to solve, which is called constipation. Clinically, constipation is difficult to treat and over-reliance on laxatives often leads to water and electrolyte imbalance, gastrointestinal dysfunction, melanosis of the colon, relaxation of anal sphincter and other problems, and even leads to colorectal cancer, diabetes, anorexia nervosa and other complications in some cases. Therefore, it is very important to find a safe and effective laxative drug or diet to improve and relieve constipation symptoms. The health promotion effect of resistant starch is mainly due to the short-chain fat and gas produced by microbial fermentation in the colon, and its role in preventing colorectal cancer and some diet-related chronic diseases is stronger than dietary fiber, and it can effectively overcome the adverse odor, rough texture, poor quality and other drawbacks of food fortified with dietary fiber. Ruminococcus bromii is a specific microorganism that degrades resistant starch. The starch decomposing enzyme of R. bromii has a unique tissue structure and forms a multi-enzyme complex. Through the adhesion protein and dockerin module, it is attached to the cell surface through the scaffold protein in the cellulose body. Big data analysis showed that the relative abundance of R. bromii in healthy people was significantly higher than that in patients with constipation. Therefore, the purpose of this clinical trial is to supplement resistant starch to patients with constipation: (1) Observe whether the symptoms of patients with constipation have improved; (2) Analyze the changes of intestinal microorganisms in patients with constipation; and (3) Verify whether the relative abundance of R. bromii is increased and analyze the correlation between the relative abundance of R. bromii in intestine and the improvement of constipation symptoms in patients with constipation.
详细描述
Human intestinal microbiota is one of the densest microbial communities on earth, including highly diverse microbial communities, which provide metabolic, immune and protective functions and play a vital role in human health. Gastrointestinal microflora is affected by many factors, including genetics, host physiology (host age, disease, stress, etc.) and environmental factors, such as living conditions and drug use. At the same time, diet is considered to be a key environmental factor mediating gastrointestinal microflora composition and metabolic function . In view of the fact that it is difficult to be digested and absorbed by the human body, probiotics can enter the intestinal tract through the digestive tract, so as to improve intestinal microecology and promote lipid, protein and mineral metabolism.
Food rich in anti-digestible starch has many functions, such as controlling body weight, reducing blood lipids and blood sugar, regulating intestinal flora and so on, which has attracted the interest of many scholars and become a new field of international food research in recent years. Resistant starch (RS) is the anti-digestion part of compound polysaccharide starch. According to the conditions of enzymatic hydrolysis resistance and starch source, the digestible resistant starch was mainly divided into four types, namely RS1, RS2, RS3 and RS4. From the cause of resistance, RS1 and RS2 have natural resistance to amylase, and the resistance can disappear after gelatinization, while the resistance of RS3 and RS4 is formed by the transformation of starch in the process of food processing or food production. RS1 can coexist with RS2 or RS3 in the same kind of food, and the existence of RS4 can increase the food intake of RS3.
Only a small part of the digestible starch can be digested and absorbed in the small intestine, providing a very low utilization rate of glucose. When most of the rest of the undigested components enter the colon, they are fermented by the intestinal microflora, mainly producing short-chain fatty acids (SCFAs): acetate, propionate and butyrate. Although both acetate and propionate have health effects, butyrate is particularly thought to improve health and is the SCFA with the largest increase in RS intake. Butyrate plays an important role in human intestinal health, including reducing inflammation, reducing the risk of colon cancer and improving intestinal barrier function. In vivo and in vitro, resistant starch diet and butyrate significantly increased the proportion of ChAT immunoreactive intermuscular neurons, intestinal neurons expressed monocarboxylic acid transporter 2 (MCT2), small interference with RNA silenced MCT2, and prevented butyrate-induced increase in the proportion of ChAT immunoreactive neurons. Butyrate and trichostatin An increased the acetylation of histone H3 in intestinal neurons. Src signal pathway inhibitors can block the effect of butyrate. Resistant starch diet increased colonic transport, and butyrate increased cholinergic-mediated contraction of colonic circular muscles in vitro. Although RS has been shown to be one of the best fibers to increase butyrate levels in the population, it is clear that not everyone can get the same benefits, and some people do not respond to RS supplementation. This suggests that differences in individual microflora play an important role in determining the outcome of RS consumption, and we need to explore more deeply the mechanism of RS digestion and how it leads to the production of butyrate. In addition, more needs to be done to understand the health effects that may be affected by RS consumption beyond butyrate levels.
Due to the complex structure of RS, certain bacteria are required to initiate the degradation of this semi-crystalline material. R. bromii and Bifidobacterium juvenis are the only known human intestinal microorganisms with RS degrading ability.
R. bromii has received attention for its role as a keystone species for RS metabolism, feeding, and/or enabling other members of the gut microbiome to access this substrate. The starch-breaking enzyme of R. bromii has a unique organizational structure and forms a multi-enzyme complex, which is attached to the cell surface through the scaffold protein in the fibrinosomes through the adhesion protein and dockerin modules, so it is called amylasome. This system has been found in a variety of human rumenococcus, and the key enzyme structure of its amylasome is highly conserved across strains. Despite its incredible ability to degrade RS, R. bromii itself does not seem to outcompete or dominate other species, but rather serves a beneficial purpose by cross-feeding other species by releasing different lengths of sugars and acetate. One study found that median fecal butyrate increased by 50% after treatment with potato starch (RS2), but further examination of individual responses revealed different changes in butyrate. A follow-up study by the same group found that those with increased R. bromii abundance in their microbiota were more likely to have a higher butyrate response to potato starch, suggesting that the right combination of primary degrading bacteria and resistant starch is needed to increase butyrate production.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —(Adult, Older Adult)
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The clinical manifestation is constipation, which meets the diagnostic criteria of Roman IV constipation.
排除标准
- •Colonoscopy excludes patients with colorectal tumors within one or two years
结局指标
主要结局
Changes in the relative abundance of species of intestinal flora
时间窗: 14 days
To analyse the changes of relative abundance of species before and after the administration of resistant starch in patients.According to the species abundance table of each species, Krona analysis , relative abundance profile display, relative abundance cluster thermogram display, PCA and PCoA dimension reduction analysis, and Wilcoxon test of different species between groups were carried out.
Changes in constipation symptoms
时间窗: 14 days
The results of the questionnaire filled out by the patients were collected and statistically analyzed, and the scores of constipation symptoms and PAC-QOL (patient assessment of constipation quality of life questionnaire) were tested by paired t-test. The higher the score, the more serious the constipation symptoms, and the lower the score means the relief of constipation symptoms. The minimum score of the scale is 0, the maximum score is 30, and a score of more than 15 can be regarded as constipation. The PAC-QOL is a specific scale for assessing the quality of life of patients with chronic constipation. The PAC-QOL consists of 28 items divided into four dimensions: worries and concerns (11 items), physical discomfort (4 items), psychological discomfort (8 items), and satisfaction (5 items). Each item was scored on a 5-point scale, and the more severe the illness, the higher the score.
Changes in the diversity of intestinal flora
时间窗: 14 days
To analyse changes in the diversity of intestinal flora before and after the administration of resistant starch in patients. Alpha diversity is a combination of species richness and evenness in a designated ecosystem. the Bray-Curtis distance reflects the variability in community composition and structure, with greater distances resulting in greater variability between communities.
Changes in the number of intestinal flora
时间窗: 14 days
Analyse the changes in the number of fecal flora before and after the administration of resistant starch in patients with constipation. In order to demonstrate more visually the changes in flora abundance after administration of resistant starch, statistical analyses were carried out using the number of patients who had a 1.5-fold increase or decrease in intestinal flora abundance before and after administration of resistant starch in all patients
Changes in the metabolic function of intestinal flora
时间窗: 14 days
According to the results of gene annotation, the ko gene family was mapped to KEGG database, and the annotation information of metabolic function was obtained, and the difference of metabolic function of fecal flora before and after taking resistant starch in constipation patients was analyzed.
次要结局
未报告次要终点
研究者
Huaping Xie
Professor
Tongji Hospital
