Chronic Stress, gut Inflammation Related

Many people globally face the pain and distress of inflammatory bowel disease (IBD). Though research on various aspects of the disease is ongoing, a formidable cure is still awaited. Moreover, the psychological state and its relation to IBD are not well understood despite the fact that stress can aggravate the condition. 

Regarding psychological stress and its adverse effect on IBD, the latest research has shed new light on how chemicals produced in the brain in response to stress activate immune cells in the gut—the cascade of events that brings trouble to people with IBD. 

The research has been published in the journal Cell. According to experts, the new findings provide valuable clues to the unknown biological mechanism leading to more gut inflammation among patients. 

The researchers, with a series of experiments on mouse models for chronic stress and IBD and then linking it to data from human patients, have found that the stress hormones can interact with neurons and glial cells present in the enteric nervous system of the gut and cause more inflammation and bowel problems. 

Christoph Thaiss, of the University of Pennsylvania Perelman School of Medicine, Philadelphia, the corresponding author of the research, said, “We found a pathway that links the perception of stress by the brain to inflammatory processes in the gastrointestinal tract.” 

Thaiss added that it is not only stress that can cause IBD. Once the disease is formed, stress can play a vital role in producing severity of it.

Thaiss and his team started by giving mice a chemical that can cause damage to the protective layers of the gut. This is a similar condition when someone develops IBD. The mice were kept in a cage with aggressive inmates so that they get psychologically stressed. 

These mice were then studied by performing colonoscopies (endoscopy of the colon) to assess their degree of inflammation. The results showed that the emotionally stressed mice had double the inflammation due to IBD. 

Next, the researchers performed experiments to understand what happens in the gut. By secreting inflammatory chemicals, immune cells can also play an important role in inflammation. For this reason, the researchers looked into how the immune cells in the gut behave in mice under stress and having IBD. 

Their experiment (they performed RNA sequencing of the gut immune cells) on these cells revealed an accumulation of monocytes along with the cytokine TNF (Tumour Necrosis Factor) in the gut. The monocytes are specialised immune cells and the TNF is a pro-inflammatory signalling molecule. 

The next question is how the stress signals from the brain travel to the colon and trigger the accumulation of the monocytes? The team found that glucocorticoid led to gut inflammation in mice with IBD and under stress. Notably, glucocorticoid is a stress hormone. 

This finding surprised the experts as it contradicted the conventional thinking that glucocorticoid treatment calms inflammation. Glucocorticoid, also a steroid, is used as a first-line treatment for IBD, writes Amy McDermott in PNAS. 

Then the researchers attempted to discover how glucocorticoid leads to the proliferation of inflammatory signals. They found that glucocorticoid does not directly induce inflammation; rather, it influences the intestinal nervous system. Chronic exposure to glucocorticoids affects the neurons and the glial cells (helper cells in the nervous system with important regulatory roles) in the gut. 

The glial cells became pro-inflammatory under chronic glucocorticoid exposure. Along with this, the proportion of immature neurons increased. The immature neurons in the gut cannot release key enzymes that induce gut motility. Remember, gut motility is the movement of food starting from the mouth to the anus. Reduced gut motility is a hallmark symptom of IBD.

With these findings, the researchers then searched for human subjects. As expected, they found severe inflammation among the patients under chronic stress. They conducted colonoscopy and biopsy of patients and also surveyed their stress levels. Their molecular analyses of the biopsies found that stressed patients have more inflammatory immune cells in the gut.