PracticeUpdate Conference Series European Congress of Psychiatry 2019

Gut Microbiota Affect and Are Affected by Depression Evidence on psychobiotics shows a promising avenue of research.

E vidence is accumulating that the state of the gut microbiome affects and reflects overall health, including psychiatric health, according to a presentation at EPA 2019. There is increasing evidence of two-way communication between the brain and the enteric nervous system. Indeed, that primary nervous system is “far more immediately aware of what’s going on in the [gut]” than is the brain, Ted Dinan, MD, PhD of University College Cork in Ireland told Elsevier’s PracticeUpdate . This brain-gut-microbiota axis of commu- nication is complex. It involves the vagus nerve and spinal pathways, short-chain fatty acids, the hypothalamic-pituitary-adrenal axis, tryptophan, and the neurotransmitters GABA, norepinephrine, dopamine, and serotonin. Making use of this knowledge is a challenge, Dr. Dinan said. “We need greater understanding of how microbes communicate with the brain; we have only rudimentary understanding.” Although Dr. Dinan stressed that evidence for the gut microbiome’s role in psychiatric illness is limited, results of his and other scientists’ research, including early studies in animals, is intriguing. “We’ve learned a lot from looking at germ-free animals,” he said. “They have no microbiota. As a result, their brains don’t develop normally;

Dr. Dinan and others believe that psycho- biotics can be considered a new class of psychotropic drugs. He cautioned, how- ever, that there is no proof of this as of yet that we should all consume nutritional supplements. One reason is that we do not yet know much about which species are beneficial. “That’s a fundamental question,” he said. “There is no consensus on that, no con- sensus on what the missing microbes are. … The key to healthy aging is maintaining diversity in microbiota,” and that is best done through a varied diet that includes foods high in prebiotics. Some examples of these foods are Jerusalem artichokes, onions, leek bulbs, jicama, wheat and potatoes that have been cooked and cooled. “In my view,” he concluded, “psychobiotics are probably not effective for severe depression – but nobody has done trials. As a practicing psychiatrist, I would like to see live biotherapeuticals developed for treating mild to moderate depression. There have been no new medications; the field has stagnated. Whether [psychobiotics] are capable of acting like and, in some circumstances, replacing antidepressants, remains to be seen.”

their serotonin system doesn’t develop normally; their blood-brain barrier doesn’t develop normally.” Dr. Dinan and colleague conducted fecal microbiota transplants in rats, using feces from depressed patients or healthy controls. The rats who received a transplant from depressed patients developed a depressive phenotype, which included alterations in corticosterone release and tryptophan metabolism. They also developed a pro- inflammatory phenotype. These experiences with animal models translate to humans. “We were one of the first groups to show that in patients attending my clinic for depression, gut microbiota differed in these patients,” Dr. Dinan said. “It was less diverse than one sees in healthy subjects.” Dr. Dinan and his colleagues have also published results from human stud- ies – for instance, “Our paper about Bifidobacterium longum 1714 showed that it reduced anxiety, decreased cortisol, and altered EEG patterns when ingested by healthy volunteers. … There are marked differences in the gut microbiota between patients with major depression and healthy controls. Patients with major depression show decreased microbial diversity.”

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EPA 2019 • PRACTICEUPDATE CONFERENCE SERIES