Meet the psychobiome

Elizabeth Pennisi does a piece on the search for new brain drugs in human poop, generated by the ~ 2 kilograms of bacteria, fungi, viruses, and archaea that live in our gut.

..with as many as 20 million genes among them, those microbes pack a genomic punch that our measly 20,000 genes can't match. Gut bacteria can make and use nutrients and other molecules in ways the human body can't — a tantalizing source of new therapies.

Holobiome, a small startup company,...plans to capitalize on growing evidence from epidemiological and animal studies that link gut bacteria to conditions as diverse as autism, anxiety, and Alzheimer's disease. Since its founding a mere 5 years ago, Holobiome has created one of the world's largest collections of human gut microbes...A growing number of researchers see a promising alternative in microbe-based treatments, or “psychobiotics,”... the targeted ailments include depression and insomnia, as well as constipation, and visceral pain like that typical of irritable bowel syndrome—conditions that may have neurological as well as intestinal components.

One interesting approach involves finding bacteria that secrete the inhibitory neurotransmitter GABA.

One growth factor Strandwitz identified turned out to be the key to launching his entrepreneurial dreams. He and colleagues isolated a bacterium that couldn't survive on typical culture media and required an amino acid called gamma-aminobutyric acid (GABA) to thrive. GABA is a neurotransmitter that inhibits neural activity in the brain, and its misregulation has been linked to depression and other mental health problems.

The researchers reasoned that if this gut microbe had to have GABA, some other microbe must be making it. Such GABA producers might be a psychobiotic gold mine. Strandwitz and colleagues began to add gut microbes one at a time to petri dishes containing the GABA eater. If the GABA eater thrived, the scientists would know they'd found a GABA producer. They discovered such producers among three groups of bacteria, including Bactereroides. They quickly filed a patent for packaging those bacteria—or their products—to treat people with depression or other mental disorders.

Before publishing those findings, the group teamed up with researchers at Weill Cornell Medicine who were doing a brain scan study of 23 people diagnosed with depression. They found that people with fewer Bacteroides bacteria had a stronger pattern of hyperactivity in the prefrontal cortex, which some researchers have associated with severe depression. The collaboration reported its findings on 10 December 2018 in Nature Microbiology, along with the discovery of GABA-producing bacteria.

GABA is too big to reach the brain by slipping across the blood-brain barrier, a cellular defense wall that limits the size and types of molecules that can get into the brain from blood vessels. Instead, the molecule may act through the vagus nerve or the enteroendocrine cells. Some researchers might question why bacteria would be any more beneficial than GABA-boosting drugs. But Strandwitz says the bacteria may do more than simply boost GABA. He notes that they produce molecules that may have other effects on the brain and body, thereby addressing other symptoms of depression.