Progress in Diagnosis And Treatment Of Primary Chronic ConstipationⅢ

Non-drug treatment is the first-line treatment for constipation. If the effect is not significant, drug treatment can be considered. Among them, anorectal biofeedback therapy has a significant effect on patients with defecation synergy disorder. At present, microecological treatment has become an effective and popular treatment method for the treatment of primary chronic constipation and has good development prospects. For constipation patients whose symptoms are severe and conservative treatment is ineffective, or who have met the indications for surgery, surgical treatment is also a last resort treatment strategy.

Click to home remedies for constipation

(1) Non-drug treatment

1. Adjust diet and lifestyle: Adjusting diet and lifestyle is often used as a first-line treatment strategy for patients with chronic constipation. The validity of this approach is based on epidemiological studies linking constipation to various dietary and lifestyle factors, such as low dietary fiber intake, low fluid intake, and lack of physical activity. The mechanisms driving the laxative effect of dietary fiber vary: large or coarse insoluble fiber particles (such as bran) mechanically stimulate the intestinal mucosa, stimulating water and mucus secretion; gel-forming soluble fibers (such as fungus, pectin) have It has a high water retention capacity, which can resist dehydration and transport water to the colon to loosen the consistency of stool [15]. Although increasing fluid intake is often recommended to improve symptoms in people with constipation, there is no evidence or controlled trials that increasing fluid intake is effective in treating constipation. Increasing physical activity in young patients with severe constipation has little benefit in relieving constipation [1]. For older patients who are significantly physically inactive, increasing physical activity as part of an overall rehabilitation program may be beneficial for constipation.

2. Anorectal biofeedback therapy: For patients with defecation synergy disorder, anorectal biofeedback therapy has been proven to be more effective than non-drug treatments (lifestyle adjustments), laxatives, or the anti-anxiety drug diazepam, with good long-term effects. It can be used as the first choice treatment for defecation synergy disorder [16]. 70% of patients respond to biofeedback therapy, which has been rated as a Level A recommendation by the American and European Society of Neurogastroenterology and Dynamics.

(2) Drug treatment

The drugs currently approved for the treatment of constipation mainly include osmotic laxatives, stimulant laxatives, secretagogues, and 5-hydroxytryptamine (5-HT) receptor agonists.

1. Osmotic laxatives: For patients with chronic constipation who are unresponsive to diet and lifestyle changes, osmotic laxatives such as polyethylene glycol and lactulose are the next commonly used treatments. Osmotic laxatives can create an osmotic gradient in the intestinal lumen, causing water and electrolytes to be secreted into the intestinal lumen, thereby reducing stool consistency and increasing stool volume [17]. The osmotic laxative polyethylene glycol was tested in several high-quality randomized controlled trials lasting up to 6 months and showed improvements in symptoms of chronic constipation compared with placebo [18]. The goal of using osmotic laxatives is to improve the patient's primary symptoms. The bacterial metabolism of unabsorbed carbohydrates can lead to gas production and abdominal cramps, which may limit the long-term use of osmotic laxatives [19].

2. Stimulant laxatives: If osmotic laxatives are not effective, you can choose stimulant laxatives for treatment. Stimulant laxatives induce the secretion of water and electrolytes, stimulate intestinal motility, release prostaglandins, and accelerate colonic transit [20]. Stimulant laxatives include diphenylmethane derivatives (bisacodyl and sodium picosulfate) and anthraquinone derivatives (senna, aloe vera), which are usually used to treat patients with urgent symptoms, such as for 2 to 3 days. patients with bowel movements [19]. One study evaluated the efficacy of various stimulant laxatives for constipation and found that bisacodyl was more effective than sodium picosulfate, prucalopride, and lubiprost in inducing more than three complete spontaneous bowel movements per week. ketone and linaclotide and other drugs [21]. Senna is also commonly used to treat chronic constipation, but no placebo-controlled trials are evaluating its efficacy. There are few long-term studies of stimulant laxatives or comparisons with other medications, and their use is often limited by adverse effects of abdominal pain and diarrhea. Clinical trials have shown that stimulant laxatives are resistant and less effective after long-term use.

3. Secretagogues: If the patient does not respond to conventional laxatives, secretagogues can be tried. Currently, available secretagogues (such as lubiprostone, linaclotide, and plicanatide) act through direct action Treat constipation by increasing fluid secretion in intestinal epithelial cells. Lubiprostone does this by activating chloride channels on luminal epithelial cells, while linaclotide and plicanatide are guanylyl cyclase C receptor agonists that increase intestinal epithelial cGMP, ultimately leading to the opening of the cystic fibrosis transmembrane conductance regulator chloride channel [22]. Li et al [23] conducted a meta-analysis and summarized 9 randomized controlled trials of lubiprostone versus placebo. The results found that the frequency of bowel movements increased and the severity of constipation was significantly improved after using lubiprostone for 4 weeks. , reduced fatigue and bloating, and overall constipation symptoms were relieved. Nausea is the most common adverse reaction of lubiprostone [24]. Linaclotide can improve intestinal and abdominal symptoms in patients with chronic constipation accompanied by moderate to severe abdominal distension. Diarrhea is the most common adverse reaction of taking linaclotide [25]. The efficacy of plicanatide is similar to that of linaclotide [26].

4. 5-HT4 receptor agonist: Prucalopride is a highly selective 5-HT4 receptor agonist that activates afferent neuron signals to increase intestinal motility. A meta-analysis of six phase III and IV randomized controlled trials showed that after 12 weeks of treatment with prucalopride 2 mg once daily, more patients with constipation had an average of 3 constipation symptoms per week compared with placebo. or more spontaneous bowel movements [27]. Prucalopride is well tolerated and has no substantial cardiovascular effects or drug interactions. Its most common adverse reactions are gastrointestinal disturbances (such as diarrhea, nausea, and abdominal pain) and headache. Veluxostat and nanafilide, like prucalopride, are selective 5-HT4 receptor agonists with prokinetic effects. These drugs have shown promise in phase II clinical trials but have not yet been evaluated further. Table 1 summarizes the commonly used drugs currently used to treat chronic constipation.

(3) Microecological treatment

In recent years, research on intestinal diseases and intestinal flora has revealed the relationship between chronic constipation and intestinal flora disorders, providing a theoretical basis for the microecological treatment of chronic constipation. Given its broad role in different gastrointestinal and non-gastrointestinal diseases, microbiota therapy has become a popular therapeutic approach among potential therapeutic agents. Microbial treatment methods mainly include probiotics, prebiotics, synbiotics, postbiotics, antibiotics, and flora transplantation.

1. Probiotics: Lactobacilli and Bifidobacteria are often used as probiotics to treat constipation. Nearly all studies on probiotics for treating constipation in adults show their effectiveness. Dimidi et al [28] found that using certain probiotic strains to change the intestinal environment may affect intestinal motility and secretion, thus benefiting patients with constipation. In addition, probiotics can relieve constipation and improve other symptoms caused by constipation. For example, probiotics protect neurons by activating protein kinase signaling pathways, thereby alleviating depression caused by constipation [29]. However, simple supplementation of probiotics does not necessarily change the human intestinal mucosal flora. Due to host specificity, probiotics and intestinal flora have different intestinal mucosal colonization resistance among different hosts [30 ], which may affect the function of probiotics. For example, in a study by Russo et al. [31] on the impact of probiotics on children with constipation, the efficacy of polyethylene glycol + probiotics was not significantly improved compared with polyethylene glycol treatment alone.

2. Prebiotics: Prebiotics are a type of non-digestible carbohydrates, such as oligosaccharides and inulin, which can increase the number of common probiotics in the human body, such as Bifidobacterium and Lactobacillus, thereby improving constipation symptoms. Currently available prebiotics include human milk oligosaccharides, lactulose, and inulin derivatives. Huang et al. [32] used lactulose to treat patients with postpartum constipation and found that constipation symptoms improved significantly better than those in the control group, including increased relief time, prolonged constipation-free days, and reduced defecation time.

3. Synbiotics: Synbiotics are biological agents used in combination with probiotics and prebiotics. The characteristic is that probiotics and prebiotics work at the same time. Synbiotics can effectively regulate intestinal flora and improve stool frequency, stool consistency, and constipation-related symptoms [33]. Bazzocchi et al [34] conducted a study on the treatment of constipation with synbiotics. They were treated with synbiotics and maltodextrin (placebo) for 8 weeks, and the results showed that patients treated with synbiotics had significant improvements in bowel movement frequency and stool consistency. In addition, colonic transit time was significantly shortened in the synbiotic group, and 5 types of Lactobacillus effective in improving constipation were found in the stool samples of half of the patients in the synbiotic group, including Lactobacillus planetarium, Lactobacillus acidophilus, and Lactobacillus rhamnosus. In the above-mentioned studies, adverse reactions including abdominal pain, bloating, nausea, and vomiting were rarely seen. Therefore probiotics, prebiotics, and synbiotics may be effective options for treating constipation.

4. Postbiotics: In 2019, the International Probiotics and Prebiotics Science Association clearly defined postbiotics: postbiotics are preparations of inanimate microorganisms and/or their components that are beneficial to the health of the host [35]. Intestinal flora can affect the host by secreting small molecules that regulate host cells and body functions, such as indole and its derivatives, and short-chain fatty acids. These small molecules are efficient means of communication in host-microbe interactions. Postbiotics can target the downstream signaling pathways that regulate microbiota based on these metabolites and act by alleviating the negative effects of excess, scarcity, or dysregulation of metabolites involved in these pathways [36]. One of the disadvantages of treatment with postbiotics is that the half-life is shorter than with live bacteria and, therefore, repeated dosing may be required to treat disorders associated with the disorder. Furthermore, due to the pleiotropic and cell type specificity of the actions of some microbiota-associated metabolites, further exploration of the full range of physiological roles of different metabolites is warranted. The efficacy of postbiotics in treating chronic constipation remains to be studied, but this metabolite-based treatment strategy is very promising.

5. Antibiotics: Previous studies have proposed a link between constipation and methanogenic bacteria. Methanogenic intestinal microbiota can lead to constipation by reducing defecation [37]. Although some studies have shown that antibiotics can be used to treat constipation, they are not the main purpose of the clinical use of antibiotics.

6. Fecal microbiota transplantation (FMT): FMT is the transfer of the entire microbial community from a healthy donor to the patient's intestine to replace the disease-related microbiome. FMT has been proven to have significant efficacy in the treatment of Clostridium difficile infection [38]. The feasibility of FMT in treating chronic constipation has been reported in many studies. Tian et al [39] conducted a randomized controlled trial in which 60 STC patients were divided into the FMT group or the control group and received conventional laxative treatment. Results showed that patients who received FMT experienced significant improvements in constipation symptoms, including bowel movement frequency and stool quality. Although the sample size was small, they demonstrated that FMT was effective in treating constipation. However, due to donor selection and the cost and complexity, FMT is unlikely to be considered the first choice. FMT should be used selectively in patients who are refractory to conventional treatment strategies.

(4) Surgical treatment

Surgical treatment of constipation has few indications and requires strict criteria. Surgery is only suitable for patients with STC and is not suitable for patients with pelvic floor dysfunction leading to uncoordinated defecation or constipation-related irritable bowel syndrome. For patients with combined defecation dyssynergia and STC, pelvic floor dysfunction must be corrected before surgical intervention becomes an option [40].

Surgical options for the treatment of slow-transit constipation include ileostomy, total colectomy with ileorectal anastomosis, antegrade cecostomy, rectocele, rectal intussusception and rectal mucosal prolapse repair, and sacral nerve stimulation [41 ]. Psychiatric consultation should be actively considered before total colectomy and ileorectal anastomosis in patients with STC combined with defecation dyssynergia, but the use of colectomy and ileorectal anastomosis rather than ileal anastomosis alone to treat constipation is controversial. Patients with combined STC and defecation incoordination may benefit from total colectomy if pelvic floor dysfunction is corrected first. In the presence of severe, uncorrectable pelvic floor dysfunction, the only surgical procedure that can provide symptom relief is terminal ileostomy. Antegrade cecostomy is preferred in children with chronic refractory constipation. Sacral neuromodulation therapy is considered an experimental therapy for the treatment of chronic constipation in adults. Domestic studies have shown that this therapy is effective in STC and has the advantages of safety and ease of operation [42].

Although primary chronic constipation is a digestive system disease, it is often complicated by mental and psychological disorders. Lack of attention to constipation and drug abuse are important factors leading to recurrence or even worsening of the disease. The diagnosis and treatment of constipation is a complex process. The accurate diagnosis of constipation subtypes is the basis for effective treatment of constipation. At the same time, it is crucial to use therapeutic drugs or strategies reasonably and standardized according to the patient's clinical symptoms and severity of the condition, which requires a more professional clinical team. At present, drugs and strategies for treating constipation are constantly improving, and emerging microecological treatments are booming. Despite this, there are still many problems. For example, the pathophysiological mechanisms of various subtypes of constipation are still unclear, and their diagnosis and treatment levels still need to be improved. In recent years, the introduction of the gut-brain-bacteria axis has shown new research ideas, suggesting that intestinal flora may be a potential treatment target for constipation in the future.

Natural Herbal Medicine For Relieving Constipation-Cistanche 

Cistanche is a genus of parasitic plants that belongs to the family Orobanchaceae. These plants are known for their medicinal properties and have been used in Traditional Chinese Medicine (TCM) for centuries. Cistanche species are predominantly found in arid and desert regions of China, Mongolia, and other parts of Central Asia. Cistanche plants are characterized by their fleshy, yellowish stems and are highly valued for their potential health benefits. In TCM, Cistanche is believed to have tonic properties and is commonly used to nourish the kidney, enhance vitality, and support sexual function. It is also used to address issues related to aging, fatigue, and overall well-being. While Cistanche has a long history of use in traditional medicine, scientific research on its efficacy and safety is ongoing and limited. However, it is known to contain various bioactive compounds such as phenylethanoid glycosides, iridoids, lignans, and polysaccharides, which may contribute to its medicinal effects.

Wecistanche's cistanche powder, cistanche tablets, cistanche capsules, and other products are developed using desert cistanche as raw materials, all of which have a good effect on relieving constipation. The specific mechanism is as follows: Cistanche is believed to have potential benefits for relieving constipation based on its traditional use and certain compounds it contains. While scientific research specifically on Cistanche's effect on constipation is limited, it is thought to have multiple mechanisms that may contribute to its potential to relieve constipation. Laxative Effect: Cistanche has long been used in Traditional Chinese Medicine as a remedy for constipation. It is believed to have a mild laxative effect, which can help promote bowel movements and induce constipation. This effect may be attributed to various compounds found in Cistanche, such as phenylethanoid glycosides and polysaccharides. Moistening the Intestines: Based on traditional use, Cistanche is considered to have moisturizing properties, specifically targeting the Intestines. Promoting hydration and lubrication of the Intestines, it may help soften tools and facilitate easier passage, thereby relieving constipation. Anti-inflammatory Effect: Constipation can sometimes be associated with inflammation in the digestive tract. Cistanche contains certain compounds, including phenylethanoid glycosides and lignans, that are believed to have anti-inflammatory properties. By reducing inflammation in the intestines, it may help improve bowel movement regularity and relieve constipation.