Of all the many ways the teeming ecosystem of microbes in a person’s gut and other tissues might affect health, its potential influences on the brain may be the most provocative. Now, a study of two large groups of Europeans has identified several species of gut bacteria that are largely missing in people with depression. The researchers can’t say whether the absence is a cause or an effect of the illness, but they showed that many gut bacteria could make or break down substances that affect nerve cell function—and maybe mood.

“It’s the first real stab at tracking how” microbial metabolism might affect psychological function, says John Cryan, a neuroscientist at University College Cork in Ireland, a vocal proponent of a microbiome-brain connection. The study “really pushes the field from where it’s been” with small studies of depressed people or animal experiments. And it is likely to encourage nascent efforts to treat depression by altering the microbiome.

Several studies in mice had indicated that gut microbes can affect behavior, and small studies of people suggested this microbial repertoire is altered in depression. To test the link in a larger group, Jeroen Raes, a microbiologist at the Catholic University of Leuven in Belgium, and his colleagues took a closer look at 1054 Belgians they had recruited to assess a “normal” microbiome. Some in the group—173 in total—had been diagnosed with depression or had done poorly on a quality of life survey, and the team compared their microbiomes with those of other participants.

Two kinds of bacteria, Coprococcus and Dialister, were missing from the microbiomes of the depressed subjects, but not from those with a high quality of life. The finding held up when the researchers allowed for factors such as age, sex, or antidepressant use, all of which influence the microbiome, the team reports this week in Nature Microbiology. And when the team looked at another group—1064 Dutch people whose microbiomes had also been sampled—they found the same two species were missing in depressed people, and they were also missing in seven subjects suffering from severe clinical depression. The data don’t prove causality, Raes says, but they are “an independent observation backed by three groups of people.”

Looking for something that could link microbes to mood, Raes and his colleagues compiled a list of 56 substances important for proper nervous system function that gut microbes either produce or break down. They found that Coprococcus seems to make a metabolite of dopamine, a brain signal involved in depression, although it’s not clear whether the bacteria break down the neurotransmitter or whether the metabolite has its own function. The same microbe makes an anti-inflammatory substance called butyrate; increased inflammation may play a role in depression. (Depressed subjects also had an increase in bacteria implicated in Crohn disease, an inflammatory disorder.)

Linking the bacteria to depression “makes sense physiologically,” says Sara Campbell, a physiologist at Rutgers University in New Brunswick, New Jersey. Still, no one has shown that microbial compounds in the gut influence the brain. One possible channel is the vagus nerve, which links that organ and the gut.

Resolving the microbiome-brain connection “might lead to novel therapies,” Raes suggests. Some physicians are already exploring probiotics—oral bacterial supplements—for depression, although most don’t include the missing gut microbes identified in the new study. Clinical neuroscientist André Schmidt of the University of Basel in Switzerland has also started a clinical trial assessing the mental health and microbiota of 40 depressed people before and after they receive a fecal transplant, intended to alter their microbiome, from a healthy donor.

Solidifying any depression-microbiome connection will take many more studies. Still, Sven Pettersson, an experimental biologist at the Karolinska Institute in Stockholm and among the first to study the brain and microbiome, calls the new work “a massive signal to the clinical community to consider microbiome profiling in their [mental health] patients.”



(원문: 여기를 클릭하세요~)



Leave a Reply

Your email address will not be published. Required fields are marked *