Irritable bowel syndrome (IBS) is a common clinical gastrointestinal disorder. According to epidemiological surveys, the number of patients with typical irritable bowel syndrome symptoms is as high as 5%-25% in the general population worldwide. The prevalence of IBS in urban residents was 10.5%, and the prevalence of IBS in rural areas was 6.14%.
The clinical manifestations are complex and diverse, mainly characterized by abdominal pain or abdominal discomfort, abnormal bowel habits and stool characteristics, and the correlation between abdominal pain or abdominal discomfort and abnormal stool. Since Pare first introduced the term IBS in 1944, modern research on the etiology, pathology and pathogenesis of IBS has been conducted for more than 50 years, but the etiology and pathogenesis of IBS are still not fully understood because of its complex clinical manifestations, diversity and recurrent symptoms without specificity. The progress of Chinese and Western medical research on the etiology and pathogenesis of this disease is briefly described as follows.
1, modern medical understanding.
(1) Psychosomatic factors: IBS has been recognized as a psychosomatic disease, and the exacerbation of IBS is closely related to psychosomatic factors. 40%-50% of IBS patients often suffer from psychological abnormalities and sleep disorders such as neuroticism, emotional agitation, restlessness, anxiety and depression. Wang et al. used the IBS-related quality of life scale to find that patients with IBS had different scores of psychiatric symptoms (significantly higher scores of depression and anxiety) than normal, and had significantly higher negative coping scores than normal, often coping with specific life events through fantasy and avoidance, and their subjective social support scores were also significantly lower than normal
The sleep quality of the IBS group was significantly lower compared to the normal group, indicating the presence of multiple psychobehavioral abnormalities in patients presenting with IBS. fass et al. investigated 505 patients and found that 50.2% of IBS patients had sleep disturbances such as easy waking and morning fatigue, and 57.2% had symptoms of waking from sleep due to abdominal pain. salmon et al. Salmon et al. found that a higher percentage of IBS patients had a history of sexual and psychological abuse than normal individuals, and concluded that childhood abuse leading to psychosis and thus physical symptoms is one of the causes of IBS.
Psychosomatic factors induce IBS mainly through the following mechanisms: (1) by affecting the vegetative nerve function, which in turn affects the ENS (enteric nervous system) and intestinal hormone secretion malfunction, thus causing intestinal motility disorders; (2) as a stress factor, causing CRF (adrenocorticotropic hormone releasing factor) release and increased vasopressin release causing increased colonic response to tension and gastrointestinal motility.
(2) Infectious factors: About 1/3 of patients with IBS have a history of acute gastrointestinal infection before their disease. Some patients infected by intestinal viruses, bacteria or parasites can develop IBS-like symptoms after the pathogens are cleared and the mucosal inflammation subsides, called post-infection irritable bowel syndrome. In the study by Zhang Houde et al. who studied 92 patients with IBS using the lactulose hydrogen breath test, it was found that 68.5% of the patients had small intestinal bacterial overgrowth, while the study by Pimentel et al. showed a correlation between the type of gas in the lactulose breath test and the subtype of IBS, and those who were positive for methane were constipated IBS. Enterobacteriaceae increased. It has also been suggested that bacterial microsomes are a cause of IBS.
The main mechanisms of infection-induced IBS are: (1) infection can act as a stressor on the central nervous system, promoting the synthesis and secretion of CRF and inducing the production of cytokines such as IL-1β, which ultimately affects gastrointestinal motility and secretion. (3) Repeated infections can induce an increase in intestinal mast cells, and mast cells, as intermediary cells of central nerves and intestinal nerves, eventually trigger a series of changes through the neuroendocrine immune network and cause IBS.
(3) Endocrine mechanism: IBS is associated with abnormal secretion of various gastrointestinal hormones and neuromediators. Patients with IBS have been reported to have abnormal levels of cholecystokinin (CCK), gastrin (MTL), 5hydroxytryptamine (5-HT), prostaglandin (PG), nitric oxide (NO), vasoactive intestinal peptide (VIP), growth inhibition (SS), substance P (SP), calcitonin gene-related peptide (CGRP), and monoamine oxidase (MAO) in plasma or tissue mucosa. -HT, MTL, VIP and PGE2 are elevated which may be the cause of IBS diarrhea.
In contrast, lowered MTL SS and increased NO may be the main cause of constipation in IBS patients. Most studies have shown a relationship between elevated CCK and abdominal pain in IBS patients. Intravenous CCK may induce episodes of abdominal pain in IBS patients. Hormones and neuromediators may play a role in the pathogenesis of IBS by affecting gastrointestinal motility and altering visceral sensitivity.
(4) Gastrointestinal kinetic factors: Gastrointestinal kinetic disorders have been considered as one of the basic pathophysiology of IBS, and many studies have confirmed that IBS patients have abnormal gastrointestinal kinetics of the esophagus, stomach, small intestine, and colon: studies of colonic electromyographic activity suggest that patients have a tendency to have enhanced intestinal segmental and group motility, and patients have increased sensitivity to colonic dilation and feeding. The cecum transit time was significantly shorter in diarrheal IBS patients and longer in constipated ones, suggesting that IBS patients may have abnormalities in both small bowel and biliary smooth muscle function. Liang et al. found that the sigmoid colon propulsive motility was enhanced in patients with diarrheal IBS under fasting conditions; the gastrocolic reflex was mainly manifested as enhanced peristaltic contractions, which occurred later and lasted longer. The gastrocolic reflex is weak and disappears quickly in patients with constipated IBS. In some people, colonic motility disorders in constipated IBS are mainly in the right hemicolectum, and colonic motility changes in functional constipation are mainly in the rectosigmoid.
Although CCK is higher in IBS patients than normal, there is impaired gallbladder emptying, and IBS patients have reduced postprandial GB excretion, significantly longer maximum GB excretion time and slower emptying rate. Gastrointestinal motility disorders may be secondary to abnormalities such as infection, immunity, and neurological injury. Current studies have not confirmed that the symptoms of IBS can be caused by gastrointestinal motility disorders alone.
(5) Immunological mechanism: T-lymphocytes CD4, CD8 and CD4/CD8 ratio are abnormal in IBS patients, and they can be restored after treatment. It is hypothesized that TNF-α stimulates the secretion of IL-8 through activation of NF-κB.
The role of mast cells in IBS has received much attention in recent years. Park et al. examined the number of mast cells in the rectal and sigmoid mucosa of 14 patients with diarrheal IBS and 14 normal controls and found that the number was significantly higher in IBS patients, with activated mast cells in close proximity to intestinal nerve fibers. Intestinal mucosal mast cells are in close proximity to nerve fibers, which contain substance P and calcitonin gene-related peptides, the latter being associated with visceral nociceptive transmission. Mast cells can be activated by infections and food antigens, psychological stress and other induced activation of secretory mediators such as 5-HT and interleukins, which ultimately affect the alteration of gastrointestinal dynamics and secretory function [32]. The intestinal mucosal mast cells are adjacent to the enteric nervous system, thereby strengthening the interconnection between the central nervous system and the enteric nerves.
Nerve afferents lead to the release of inflammatory mediators from intestinal mucosal mast cells degranulation, which excite intestinal stimulatory secretory neurons and inhibit the release of norepinephrine from post-sympathetic axons, thus explaining stress-induced secretory diarrhea and abdominal discomfort. In conclusion, mast cells, as an ideal antigen receptor in the intestine, may play an important role in IBS.
(6) Visceral hypersensitivity: abnormal visceral sensitivity in IBS patients has received increasing attention in recent years, and more and more evidence suggests the existence of a state of visceral hypersensitivity in IBS patients. Zou Duowu et al. found that the sensory threshold, defecation threshold, and pain threshold of the anorectum of IBS patients were significantly lower than those of normal subjects, and may be related to mast cells.
The study by Qing Li et al. showed that abdominal cold stimulation had no significant effect on visceral sensory thresholds in IBS patients, while intrarectal cold stimulation significantly decreased the initial rectal sensory thresholds, suggesting that sensory hypersensitivity in IBS patients is not due to a decrease in overall pain threshold, but only to visceral sensory hypersensitivity.
(7) Other factors: IBS is associated with genetics, diet, season, environment, menstrual cycle, lifestyle, education, gender and abdominal surgery, etc. IBS is more common in women and symptoms are more frequent during menstruation. Eating foods containing lactose, caffeine, alcohol, and gas-prone foods have been reported to worsen the symptoms of IBS patients. Hasler et al. found that the prevalence of IBS is higher in people who have had abdominal surgery, indicating that abdominal surgery is also a risk factor for IBS.
2.Traditional medical understanding
(1) Chinese medicine etiology and pathogenesis: Chinese medicine does not have the name of irritable bowel syndrome. The cause of the disease is mainly emotional and mental disorders, internal invasion of external evil, physical weakness, and poor diet.
IBS is mostly triggered by emotional disorders, the seven emotions in Chinese medicine, happiness, anger, sadness, pity, fear and shock, of which the liver is most closely related to emotional irritation and change. “Most people believe that the disease is caused by the liver, the symptoms are in the intestine, and the system is in the liver. Emotional and mental disorders lead to liver depression and qi stagnation, and liver and spleen disorders lead to adverse intestinal qi flow, resulting in abdominal pain, diarrhea, constipation and other symptoms.
For example, Zhang Hong believes that this disease is mainly caused by liver depression and spleen deficiency, but there are also liver depression, spleen deficiency and liver depression and spleen deficiency combined. Hu et al. believe that the disease is related to the three organs of the liver, spleen and stomach, with the liver being the key, and that abdominal pain and constipation in IBS is caused by stagnation of Qi and blood. Zhou’s and Xie’s believe that the deficiency of spleen yin also plays an important role in the deficiency of spleen yin, as the body’s adaptability decreases and the spleen and stomach cannot tolerate heavy loads. Chen Weihong et al. suggested that in addition to liver-depression and spleen-deficiency, there is also damp-heat within the body, while Guo suggested that there is also a wind evil, and that IBS should be treated as intestinal wind. Weakness of the spleen and stomach is another major etiological mechanism leading to IBS.
As a result of the disease of the spleen and stomach or physical exertion and excessive thinking can damage the spleen and stomach, abdominal distension can occur due to loss of spleen health, and diarrhea can occur due to spleen deficiency and dampness. In addition, some people believe that IBS is related to the deficiency of spleen and kidney yang. Lin believes that the kidney yang cannot warm the spleen yang, and that the internal growth of dampness and turbidity, which blocks the qi flow, is one of the pathogenic mechanisms of IBS.
(2) Modern research on the etiology and pathogenesis of Chinese medicine
It is one of the current research directions to study the various types of IBS by means of modern medicine to reveal their essence and provide modern theoretical support for the etiology and pathogenesis of TCM and provide the theoretical basis for the treatment of IBS in TCM. Xie Jianqun et al. found that the abnormally elevated MOT of IBS patients could be normalized by using the method of dredging the liver and strengthening the spleen. It indicates that there is a consistency between the TCM liver and spleen imbalance in IBS and the abnormal gastrointestinal hormone secretion in modern medicine. Chen Yongping et al. measured the concentrations of SP and VIP in plasma and sigmoid mucosa of patients with IBS with spleen deficiency and liver-gut qi stagnation, and found that plasma SP decreased and VIP increased in IBS with spleen deficiency and dampness, while plasma SP increased and VIP decreased in IBS with liver-gut qi stagnation. This is also indicated.
3. Conclusion
In conclusion, IBS is a multi-causal, multi-phase gastrointestinal functional disease, and its etiology and pathogenesis are very complex and not well understood yet. At present, there are few basic studies on IBS in China, especially from multiple perspectives, and more extensive and deeper studies need to be conducted in collaboration with multiple parties. Further research should strengthen the study of visceral sensory hypersensitivity, understand the different transmitters and their action sites affecting the visceral afferent pathways from the peripheral and central aspects, so as to clarify the status of visceral sensory hypersensitivity in the pathogenesis of IBS.
Although TCM has good curative effect on this disease, there is no unified standard for the understanding, diagnosis and efficacy evaluation of this disease in TCM. Further research should establish the criteria for diagnosis and efficacy of IBS in TCM as soon as possible, strengthen the understanding of the etiology and pathogenesis of IBS from the perspective of the combination of disease and evidence, and recognize, evaluate and explore the pathogenesis of IBS and the therapeutic mechanism of IBS in TCM from the correlation between the neuro-endocrine-immune network and the overall concept of TCM.
With the development of neuro-endocrine-immune network and brain-gut axis theory and the deepening of the research on the role of mast cells in IBS, there will be a deeper understanding of the pathogenesis of IBS, and TCM as a holistic treatment will play an important role in the treatment of IBS.