How long-term stress impacts the intestine 

Chronic psychological strain and pressure can precipitate inflammation and dysmotility in the gut, details a recent study published in Cell journal; important for future research and clinical practice, say doctors in India

June 09, 2023 11:33 am | Updated 11:34 am IST

The crossroads of mental health and gastroenterology got a lot more attention in May this year, with a study published in Cell journal, titled ‘The enteric nervous system relays psychological stress to intestinal inflammation’. “Mental health profoundly impacts inflammatory responses in the body. This is particularly apparent in inflammatory bowel disease (IBD), in which psychological stress is associated with exacerbated disease flares,” it said, in summary.

The Gist
A new study published in Cell journal shows how psychological stress leads to intestinal inflammation.
It describes the two pathways for the inflammatory response and the whole cascade which ultimately precipitates the disorder.
Chronic stress results in both physical changes to the intestine and a chemical imbalance resulting in functional changes to the intestine.
Psychiatrists prescribe GI-directed behavioural therapies that use cognitive behavioural approaches to improve symptom-specific anxiety, such as aerobic exercise and yoga.

“It’s an important study. What is excellent is that for the first time we have a much clearer understanding of the possible underlying mechanisms of inflammatory response and the whole cascade which ultimately precipitates the disorder. This is good not only for researchers but also for clinicians, because the pathways have been quite well explained,” says Sarath Gopalan, senior consultant paediatric gastroenterologist and hepatologist, Madhukar Rainbow Children’s Hospital, Delhi. In the future, he feels, with more research, drugs that block inflammatory cascades can be developed.

Stress fracture

The study talks of stress pushing the adrenal gland to make glucocorticoids, a steroidal stress hormone. When stress is short-term, like before an exam, it may result in a loss of appetite and increased frequency of stools. When it’s chronic, or experienced long term, over a few weeks to months to years, like in a toxic job or marriage or through childhood with the pressure to perform, it can result in inflammation of the gastrointestinal tract, an example being inflammatory bowel disease (IBD).

With chronic stress, the body is constantly producing glucocorticoids. Two mechanisms may kick in, though the study does not describe whether both occur together or if there is a difference in the pace: “One is mediated by monocytes (white blood cells in the immune system that kill invaders) and TNF (tumour necrosis factor, a protein made by white blood cells), both mediators of inflammation through colony stimulating factor-1 (CSF-1, signalling pathways),” explains Gopalan. This results in physical changes to the intestine – damage to the intestinal mucous membrane due to the inflammation.

“The second is associated with neurotransmitter acetylcholine deficiency and dysmotility (abnormal speed of intestinal movement due to improper functioning of the muscles in the area). This is mediated through another inflammatory mediator: transforming growth factor (TGF) beta 2,” says Gopalan. This is the functional change in the gut.

Two disorders

IBD is quite different from irritable bowel syndrome (IBS) that is also precipitated by stress, and seen a great deal in women. Unlike IBD though, IBS does not cause, and neither is it caused by an inflammatory response. “If I do an endoscopy, a person with IBD will have physical changes to the colon; it may present like a wounded intestine – there may be ulcers for instance. There are morphological or structural changes. However, in IBS (characterised by bloating, constipation, diarrhoea) you won’t see any of that,” says Gopalan, adding that the IBD is caused by multiple factors, one of which is stress. “IBD is immunologically mediated (relating to the immune system) and can be hereditary.” Ulcerative colitis and Crohn’s disease are two examples of IBD and bear the risk of colorectal cancer, while IBS is a part of a larger clutch of disorders of the gut-brain interaction (DGBI).

Also read: Does gravity have anything to do with IBS?

In a study published in Neurogastroenterology and Motility journal around ‘Medical students’ knowledge and perception of irritable bowel syndrome in comparison to inflammatory bowel disease’, it was found that “Biases observed in gastroenterologists toward patients with IBS originate as early as the beginning of medical school, including seeing IBS as a “less real” disease and more difficult to treat.”

Dual brains

What the study also does is to draw attention back to the way stress impacts the body, particularly the GI system. “There are two brains: the big brain and the small brain (nerves in the intestine),” says Shobna Bhatia, who heads gastroenterology at NIMS University, Jaipur, and is a member of the Rome V committee, The Rome Foundation, a global institution that provides medical information on the disorders of the gut-brain interaction (DGBI). The gut-brain axis is controlled by the parasympathetic nervous system (the vagus nerve that regulates internal organ functions like digestion), and the sympathetic nervous system located across the body. Both are connected with the enteric nervous system located in the gastrointestinal system (the small brain). The two brains ‘talk’ to each other (exchange information), hence stress occurring in the big brain can cause changes in the small brain (butterflies in the stomach before an exam).

Also read: Stress and how to beat it

“Physiologically, stress affects the hypothalamus-pituitary-adrenal (HPA) axis, activates the sympathetic nervous system, releases inflammatory cytokines and cortisol. There are individual differences in the way it is perceived based on one’s genetic vulnerability, experience, and development,” says Alok Kulkarni, senior consultant psychiatrist at Manas Institute of Mental Health and Neurosciences, Hubli. “Chronic low-grade stress keeps the HPA axis activated.” This has an impact on both IBS and IBD.

Good and bad news

Problems with the GI tract are usually easier to detect in children, because there’s parental supervision, says Gopalan. “If the parents don’t pick it up, the teacher might. With adults, it’s harder, because there’s no one monitoring them.”

Kulkarni says there are specific GI-directed behavioural therapies that use cognitive behavioural approaches to improve symptom-specific anxiety. “We cannot eliminate stress; we can only evolve mechanisms of coping better with stress,” he says, adding that aerobic exercise and yoga play a big role in dissipating stress. “Aerobic exercises release endorphins which not only boost mood, but also helps in coping better with pain. A regular yoga practice boosts brain-derived neurotrophic factor (BDNF) levels, important in learning and memory. Yoga also induces a relaxation response.”

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