Gut And Mind - How They Are Connected

"In order to swallow, you need input from the brain. To go to the toilet, you need input from the lower spinal cord," explains Ulrika Marklund , Docent at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet.

The discussions between these two' brains' take place via what is known as the gut-brain axis - a collective term for the various pathways through which messages can travel. Signals may pass through the nervous system, but they can also travel via the bloodstream.

The enteric nervous system operates independently

The enteric nervous system also has the ability to operate independently of the brain's input. Certain nerve cells detect what is happening in the gut, what we eat, or whether an infection is brewing. Others relay information to neighbouring cells, or adjust the speed of gut movements, or trigger the lining of the gut to secrete more fluid. In the small and large intestine, the system works entirely on its own. A striking demonstration comes from experiments on mice: if you remove a section of intestine, the movements continue for an hour or so, even outside the body.

"If you insert a pellet at one end, it will come out at the other," says Ulrika Marklund.

Sometimes, though, things go wrong. In Hirschsprung's disease, for instance, the lower part of the colon completely lacks an enteric nervous system - a congenital defect. The result is blockage: stool cannot pass. The condition is often detected in newborns when no meconium appears in the nappy. Today, the faulty section of bowel is surgically removed, but many live with ongoing problems.

"Ideally, you would need to build an entirely new nervous system. There is now great hope that stem cell therapy could make this possible," says Marklund.

Her own research - mapping the different types of nerve cells in the enteric nervous system, how they form and connect - could help here. It may also prove useful in gastroparesis, where the stomach empties too slowly and, in severe cases, causes malnutrition. This is relatively common in people with long-standing diabetes, due to nerve damage.

"If we understand how nerve cell types form and cooperate, we might be able to guide stem cells to become specific nerve cell types that could be used to treat these conditions," she explains.

Drugs targeting the brain often affect the gut

Medication can also disrupt communication between the brain and the abdominal brain. Just like the brain, the gut is packed with nerve cells, using exactly the same neurotransmitters. That is why drugs targeting the brain often affect the gut too. SSRIs, prescribed for depression and which increase serotonin levels, can overstimulate the enteric nervous system - leading to diarrhoea. Opioids have the opposite effect, slowing the system down and causing constipation.

In recent years, scientists have also begun to understand the interplay between the brain, the abdominal brain and the immune system.

"Most of the studies showing this have been done in mice, but it is likely to work similarly in humans," says Marklund.

Stress also seems to disrupt enteric signalling. Prolonged stress stimulates glial cells in the abdominal brain. These release molecules that influence macrophages - immune cells - which can trigger inflammation. This may explain why people with inflammatory bowel disease often experience flare-ups during stressful periods.

Fatty acids from the gut reach the brain

An increasing body of research - though mostly in animals - also suggests that conversations between brain and gut can travel via the blood. The inner wall of the gut is coated with a thick, mucus-like layer that protects it from contents. Within the gut lives a teeming community of microorganisms with diverse roles. Bacteria produce chemical substances - neurotransmitters and metabolites. Some act on nerve cells in contact with the gut wall, others interact with immune cells, and some penetrate the mucosal barrier into blood vessels, travelling through the body. Short-chain fatty acids are one example.

"Eventually, some reach the blood-brain barrier and can enter brain tissue," says Catharina Lavebratt , Docent at the Department of Molecular Medicine and Surgery at Karolinska Institutet.

These fatty acids are thought to influence brain function, though the details remain unclear. Researchers are now investigating whether levels of short-chain fatty acids, or other metabolites from the gut microbiota that cross the blood-brain barrier, play a role in brain and mental health. What happens if the gut lining is damaged, by infection, for

instance, or if the microbiota itself is altered, perhaps after antibiotics or unhealthy diet? In such cases, the brain may receive "incorrect" signals - "incorrect" in the sense that, according to numerous studies, behaviour may be affected, explains Catharina Lavebratt.

"Children and adults with ADHD have been found to have lower levels of short-chain fatty acids in the blood compared with others," she says.

Link between gut flora and ADHD being studied

Several studies now show that children with autism, and also ADHD, have a different gut microbiota compared with others, at least at group level. Research from Karolinska Institutet and Linköping University has found that children with early disturbances in gut flora are more likely to develop autism or ADHD. Yet it is still unclear whether the microbiota is linked to behaviour, or why it differs in these groups.

"Diet, medication and genetic inheritance may all play a part. More studies are needed to understand whether gut flora contributes to these diagnoses, and whether short-chain fatty acids or other metabolites are involved," says Catharina Lavebratt.

She has tried to shed light on this. One of her register studies, covering a million births in Finland, suggests that antibiotics during pregnancy may be linked to increased risk of ADHD in children, but not autism. However, such a study cannot prove causation; other factors may be responsible.

Animal findings, however, are clear. Research on mice given antibiotics shows that a completely or partly disrupted gut flora affects behaviour.

"Hyperactivity, withdrawal and anxious behaviour have all been observed," she notes.

In an ongoing study, she is testing whether ADHD symptoms can be reduced by giving newly diagnosed children a probiotic containing lactic acid bacteria and dietary fibre. In a previous placebo-controlled study led by her, both children and adults with ADHD showed fewer psychiatric symptoms after a course of probiotics. A similar European study, involving participants from three countries, found comparable results in adults with ADHD.

Earlier studies have shown that people with neuropsychiatric diagnoses are generally more sensitive to poor sleep and poor diet. It is therefore common for those with ADHD to be advised to consider lifestyle changes to find balance. Dietary changes that affect gut flora may be particularly important, Catharina Lavebratt believes. For now, however, she advises people with ADHD to follow the recommendations of the Swedish National Food Agency.

"The impact of diet on ADHD symptoms probably varies between individuals depending on genetic factors, among other things. But the recommended diet is good for the body overall. We simply do not yet know what role it plays in symptoms," she says.

Pain even though everything looks fine

Irritable bowel syndrome (IBS), which causes pain, discomfort and frequent or infrequent trips to the loo, is also thought to stem from disrupted communication between the brain and the gut. IBS and several other bowel conditions without a clear medical explanation are often called functional disorders, but increasingly the term "disorders of gut-brain interaction" (DGBI) is used. This reflects how nerve pathways between gut and brain start sending signals of pain and discomfort - even when everything looks fine. Exactly what goes wrong in gut-brain signalling, and why, remains unknown.

For some affected individuals, medication that calms the gut or eases pain can help to a degree. For others, dietary changes may relieve symptoms, though rarely eliminate them. A major problem is that symptoms can actually worsen if people change their behaviour in an attempt to avoid discomfort.

"It is common for those who have had bad experiences with pain or diarrhoea to develop strategies. They may start avoiding certain foods or activities as a precaution," says Brjánn Ljótsson , Professor of Clinical Psychology at the Department of Clinical Neuroscience, Karolinska Institutet.

Avoidance behaviour risks making gut problems worse - a clear sign the issue is not confined to the gut.

"I often say that if you start behaving as though your stomach is a threat, you will get more symptoms," he explains.

Training the brain to be more alert to what is happening in the gut can heighten vigilance, which in turn may activate the fight-or-flight response - and worsen symptoms. Everyone who has ever felt nervous knows the stomach can become unsettled too.

Psychological treatment can help

For people whose daily lives are restricted by IBS, psychological treatments such as cognitive behavioural therapy (CBT) can be a good option.

"Therapy involves gradually challenging fears and discovering that you can carry out activities despite symptoms. Often it works better than expected, and the brain relearns," says Brjánn Ljótsson.

CBT not only makes symptoms easier to manage - it also seems to influence gut function.

"We see fewer problems with diarrhoea, pain and bloating," he notes.

Not everyone benefits from CBT. For them, another form of psychological treatment, so-called gut-directed hypnosis, may help. In this therapy, the patient is guided into a deeply relaxed, hypnotic state. A licensed hypnotherapist first leads the patient into hypnosis, then provides instructions on how to visualise their gut movements. The aim is partly to give a sense of control over the gut, and partly to help reinterpret symptoms in a different way. Over time, after several hypnosis sessions, these new interpretations are intended to carry over into everyday life. Gut-directed hypnosis is already used in several regions of Sweden. But it is no miracle cure - not everyone improves noticeably.

"But a meta-analysis we carried out a few years ago shows that, nonetheless, hypnosis is, effective for many," says Brjánn Ljótsson.