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Disorders of gut-brain interaction
Disorders of gut-brain interaction
The way we respond to life’s stressors have strong implications for our psychological and physiological well-being. In terms of the latter, gastrointestinal (GI) function is particularly affected by stress. 5
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Common GI symptoms due to stress include heartburn, indigestion, nausea, vomiting, diarrhoea, constipation and associated lower abdominal pain. 5
What is stress?
According to the American PsychiatricAssociation, stress can be defined as “a sense of being overwhelmed, worried, pressured, exhausted, and lethargic”. Stress influences people of all ages, gender, ethnicity, and socioeconomic groups. 3,4,6
Studies show that 20%-90% of the general population is exposed to one or more extreme stressful event in their life. We are currently experiencing one of the most stressful periods inhuman history. Since the outbreak of Covid-19, the prevalence of stress has increased globally in the general population. Uncertainty, fear, and social isolation due to strict lockdown regulations, are some of the top stressors.1,2
What worries the world now?
Global polling firm, Ipsos recently published the findings of their What Worries the World survey, which tracks public opinion on the most important social and political stressors across 27countries. They found that:2
» 47% of respondents indicated that Covid-19 is one of the biggest issues facing their countries
» 38% are stressed about unemployment
» 29% said poverty and social inequality stress them the most
» 27% expressed concerns about financial and political corruption
» 26% were worried about crime and violence.
In South Africa, the picture looks a bit different.
These were the five biggests stressors for South Africans in 2020.
» 59% ofrespondents were stressed about unemployment
» 59% indicated that corruption was a major stressor
» 58% replied they were stressed about crime and violence
» 29% said poverty and social inequality were their biggest source of stress
» 24% were stressed about Covid-19.
But it is not always the ‘big’ issues that cause the most stress. Work-related stress has increased exponentially over the last century because of industrialisation and globalisation, according to the International Labour Organization. In Europe for example, between 50% and 60% of all lost working days were stress-related.9
A study by the American Institute of Stress found that 25% of workers viewed their jobs as the number one stressor in their lives, 80% felt stressed on the job, nearly 50% indicate that they needed help in learning how to manage stress, and 25% felt like “screaming or shouting”because of job stress.10
Apart from work-related stress, stress can also be triggered by everyday events such as a fight with a loved one or an exam. These are examples of external factors. It can also be caused by internal factors such as negative emotions and feelings (pain or sadness).5
A sudden or short-term, acute stressor provokes a fight or flight response – the brain’s way to ensure survival. When the stressor passes, negative feedback is triggered to terminate the stress response and to bring the body back to a state of steady internal, physical, and chemical conditions (homeostasis).8
However, some individuals do not achieve homeostasis, which may lead to the onset of psychiatric disorders (eg depression, anxiety, post-traumatic stress disorder [PTSD] or acute stress disorders), which in turn negatively affect physiological health (eg changes in GI functioning, brain activity, pain modulation, and the cardiovascular system).1,6,8
The gut-brain axis
As mentioned already, GI function is particularly sensitive to stress. Early as well as late life stress have been linked to the onset, as well as the severity of symptoms in several chronic disorders of the digestive system. Patients with irritable bowel syndrome (IBS) and functional dyspepsia (FD) - two of the most common functional gastrointestinal diseases (FGIDs) –are particularly affected.5,6
The GI tract and central nervous system(CNS) constantly communicate with each other. This bidirectional relationship is influenced by a number of complex pathways including the immune system, the hypothalamic-pituitary axis(HPA), and gut microbiota.5,6
Stress can result in overactivity or underactivity along the HPA and the autonomic nervous system, as well as the metabolic, and immune systems, resulting in alteration in brain-gut interactions, ultimately affecting different physiological functions of the GI tract.8
The prefrontal cortex, the limbic system (eg the hippocampus and the amygdala) and the hypothalamus are the main brain areas involved in the stress response. The amygdala is involved in the stress effect on the GI tract. The amygdala receives information from the gut, through the parabrachial nucleus and the dorsal vagal complex, and can modulate the sympatho-vagal balance, a marker of brain-gut interactions.7
Impact of stress on the gut
Stress has been shown to cause slowing of gastric emptying, increase in distal colonic motility, and acceleration of intestinal transit. In IBS and FD, persistent alterations of autonomic responsiveness likely play a role in altered bowel habits and alteration in gastric emptying, respectively.6
Irritable bowel syndrome
IBS affects 11% of the global adult population.IBS is characterised by abdominal pain, experienced on average at least once per week, and pain that is associated with two or more of the following characteristics:
» Defecation
» Changes in the frequency of stool
» A change in the form of the stool.
These characteristics should be present for at least three months, with symptom onset at least six months before diagnosis.11,13
The prevalence of IBS – especially IBS constipation- is higher in women (60%-75%)than men. It has been postulated that the role of sex hormones in the stress response, colonic motility, epithelial barrier function, immune activation, and several regulatory mechanisms of the gut-brain axis, may account for this gender difference.11
Patients with IBS have a high prevalence (40%-80%) of at least one comorbid psychiatric condition (eg anxiety and depression). A 2013study also showed that IBS patients experience an increase in stress prior to progression from an IBS non-patient to an IBS patient.11
The study found that stress caused by for example the end of a relationship, a divorce, ora family member leaving home, were frequently reported 38 weeks prior to the onset ofIBS symptoms.11
Functional dyspepsia
FD affects between 27%-40% of the general population. FD is characterised by the presence of permanent or periodic symptoms such as upper abdominal pain, nausea, a feeling of burning in the stomach area, fullness in the stomach and early satiety. Symptoms appear at least six months before diagnosis, last at least three months in the absence of an organic disease that explains the appearance of these symptoms.12,13
Numerous studies have investigated stress as a risk factor for the development of FD, but most studies focused on ‘big’ events rather than everyday stress. Deding et al’s study focused on the effects of everyday stress and whether it plays a role in the onset or FD, or whether it affects the severity of symptoms.12
Of the 23 698 participants, 2547 fulfilled the Rome IV criteria for FD or IBS. The team found that FD patients had significantly higher median stress scores compared to controls and felt more stressed and more susceptible to stress.12
During the 33 months of follow-up, FD patients, who experienced the highest levels of self-perceived everyday life stress, visited their healthcare professionals more and filled more prescriptions compared to the other groups.12
The group with the second lowest stress level had an increased risk of FD of 1.16. The group with the third and second highest stress levels had an increased risk of 1.2 and the group with the highest stress level had an increased risk of 1.3.12
The proportions of FD patients in the stress level groups ranged from 11.6% to 24.9%. The researchers concluded that while stress play a role in the onset of IBS, in FD, stress affects symptom severity. Healthcare professionals should be aware of stress signals in patients with FD symptoms, noted the researchers.12
Treatment of stressrelated GI disorders
Effective management of FGIDs requires a biopsychosocial approach, say the experts. The biopsychosocial approach focuses on the complex mix of environmental (eg influence of the patient’s family, the individual’s own psychological states and traits) and physiological factors.13,14
Healthcare professionals must consider and address all these factors to effectively manageFGIDs. The treatment plan should be guided by the nature of symptoms, severity, the presence of psychosocial comorbidities and their impact on the patient. The effectiveness of treatment largely depends on the patient–provider relationship.13,14
An effective patient–provider relationship improves patient and provider satisfaction, adherence to treatment, symptom reduction, and improved clinical outcomes.13
Stress modification, psychotherapy and hypnosis appear helpful for IBS and FD symptoms. Tricyclic antidepressants also appear effective for IBS and other functional bowel symptoms, even in low doses. Recent evidence indicates the medication may work by reducing the brain’s response to intestinal pain during stress.5
Sedatives such as the benzodiazepine can reduce the effect of stress on the gut. Studies have shown that under stressful conditions, chlordiazepoxide blunted the colonic motor response to mental stress in IBS patients. This effect may explain the benefits of combined sedative-anti-spasmodic medications for IBS.5
Conclusion
Stress has been shown to play a major role in FGIDs - especially in patients with IBS and FD. Short- and long-term exposure to stress can
trigger IBS and exacerbates symptom severityin FD. Healthcare professionals should takecognisance of the psychological ‘make-up’of patients and incorporate strategies thataddresses stress.
References
1. Fanai M and Khan MAB. Acute Stress Disorder. StratPearls (Internet), 2021.
2. Ispos. What worries the world today? https://www.ipsos.com/sites/default/files/ct/news/documents/2020-12/www-summary-december-2020.pdf
3. America Psyhological Association. What’s the difference between stress and anxiety? Knowing the difference can ensure you get the help you need. https://www.apa.org/topics/stress/anxiety-difference
4. Shahsavari MA, Abadi EAM, Kalkhoran MH et al. Stress: Facts and Theories through Literature Review. International Journal of Medical Reviews, 2015.
5. Mertz H. Stress and the Gut. http://www.med.unc.edu/ibs/files/2017/10/Stress-and-the-Gut.pdf
6. Mayer EA. The neurobiology of stress and gastrointestinal disease. Gut, 2000.
7. Bonaz B, Pellissier S, Sinniger V et al. The Irritable Bowel Syndrome: How Stress Can Affect the AmygdalaActivity and the Brain-Gut Axis. IntechOpen, 2012.
8. Qin H-Y, Cheng C-W, Tang X-D et al. Impact of psychological stress on irritable bowel syndrome. World J Gastroenterol, 2014.
9. International Labour Organization. Workplace Stress.https://www.ilo.org/wcmsp5/groups/public/---ed_protect/---protrav/---safework/documents/publication/wcms_466547.pdf
10. The American Institute of Stress. Workplace Stress. https://www.stress.org/workplace-stress
11. Carco C, Young W, Gearry RB et al. Increasing Evidence That Irritable Bowel Syndrome and Functional Gastrointestinal Disorders Have a Microbial Pathogenesis. Front Cell Infect Microbiol, 2020.
12. Deding U, Torp-Pedersen C, Boggild H et al. Perceived stress as a risk factor for dyspepsia: a register-based cohort study. European Journal of Gastroenterology & Hepatology, 2017.
13. Ivashkin VT, Poluektova EA, Glazunov AB et al. Pathogenetic approach to the treatment of functional disorders of the gastrointestinal tract and their intersection: results of the Russian observation retrospective program COMFORT. BMC Gastroenterology, 2020.
14. Black CJ, Drossman DA, Talley NJ et al. Functional gastrointestinal disorders: advances in understanding and management. The Lancet, 2020. SF
