Links between Gut Microbes and the Brain Development and Behavior

Researchers have drawn links between gastrointestinal pathology and psychiatric neurological conditions such as anxiety, depression, autism, schizophrenia and neurodegenerative disorders—but they are just links.

“In general, the problem of causality in microbiome studies is substantial,” says Rob Knight, a microbiologist at the University of California, San Diego. “It's very difficult to tell if microbial differences you see associated with diseases are causes or consequences.” There are many outstanding questions. Clues about the mechanisms by which gut bacteria might interact with the brain are starting to emerge, but no one knows how important these processes are in human development and health.

That has not prevented some companies in the supplements industry from claiming that probiotics—bacteria that purportedly aid with digestive issues—can support emotional well-being. Pharmaceutical firms, hungry for new leads in treating neurological disorders, are beginning to invest in research related to gut microbes and the molecules that they produce.

Scientists and funders are looking for clarity. Over the past two years, the US National Institute of Mental Health (NIMH) in Bethesda, Maryland, has funded seven pilot studies with up to US$1 million each to examine what it calls the 'microbiome–gut–brain axis' (Knickmeyer's research is one of these studies). This year, the US Office of Naval Research in Arlington, Virginia, agreed to pump around US$14.5 million over the next 6–7 years into work examining the gut's role in cognitive function and stress responses. And the European Union has put €9 million (US$10.1 million) towards a five-year project called MyNewGut, two main objectives of which target brain development and disorders.

The latest efforts aim to move beyond basic observations and correlations—but preliminary results hint at complex answers. Researchers are starting to uncover a vast, varied system in which gut microbes influence the brain through hormones, immune molecules and the specialized metabolites that they produce.

“There's probably more speculation than hard data now,” Knickmeyer says. “So there's a lot of open questions about the gold standard for methods you should be applying. It's very exploratory.”

Gut reactions

Microbes and the brain have rarely been thought to interact except in instances when pathogens penetrate the blood–brain barrier—the cellular fortress protecting the brain against infection and inflammation. When they do, they can have strong effects: the virus that causes rabies elicits aggression, agitation and even a fear of water. But for decades, the vast majority of the body's natural array of microbes was largely uncharacterized, and the idea that it could influence neurobiology was hardly considered mainstream. That is slowly changing.

Studies on community outbreaks were one key to illuminating the possible connections. In 2000, a flood in the Canadian town of Walkerton contaminated the town's drinking water with pathogens such as Escherichia coli and Campylobacter jejuni. About 2,300 people suffered from severe gastrointestinal infection, and many of them developed chronic irritable bowel syndrome (IBS) as a direct result.

During an eight-year study of Walkerton residents, led by gastroenterologist Stephen Collins at McMaster University in Hamilton, Canada, researchers noticed that psychological issues such as depression and anxiety seemed to be a risk factor for persistent IBS. Premysl Bercik, another McMaster gastroenterologist, says that this interplay triggered intriguing questions. Could psychiatric symptoms be driven by lingering inflammation, or perhaps by a microbiome thrown out of whack by infection?

Recent studies also demonstrate that gut microbes directly alter neurotransmitter levels, which may enable them to communicate with neurons. For example, Elaine Hsiao, a biologist now at the University of California, Los Angeles, published research this year examining how certain metabolites from gut microbes promote serotonin production in the cells lining the colon—an intriguing finding given that some antidepressant drugs work by promoting serotonin at the junctions between neurons. These cells account for 60% of peripheral serotonin in mice and more than 90% in humans.

To read the entire article The Tantalizing Links between Gut Microbes and the Brain, from Scientific American  click here