Down in the dumps? A shot of friendly bacteria could give you the boost you need

It was meant to be a new way to fight cancer. The idea was that injecting a certain bacterium into people would stimulate their immune systems to destroy tumours. Unfortunately, the treatment had little effect on the survival of the terminally ill lung cancer patients in the first trial. It did have one unexpected effect, though: those injected with the bacterium experienced a radical improvement in their mood and quality of life.

"It was supposed to be a double-blind study, but the investigators could nearly always tell who was on the genuine treatment because their whole attitude, their demeanour, changed," says Charles Akle, chair of Immodulon Therapeutics in London, UK. "They just looked better."

How can injecting a bacterium brighten someone's mood? We don't yet know all the details, but animal studies suggest that the immune response triggered byMycobacterium vaccae causes neurons in the prefrontal cortex to release large amounts of serotonin, boosting mood and well-being (Neuroscience, vol 146, p 756). This might seem odd, given that immune stimulation can also lead to depression (see opposite), but our relationship with M. vaccae goes back a long way. Such "old friends" are thought to prime the immune system in interesting ways. "We think M. vaccae is inducing regulatory cells which will dampen down and terminate unwanted inflammatory responses," says Graham Rook of the Royal Free and University College Medical School in London.

Whatever the mechanism, the discovery adds to the growing evidence that bacteria affect our mind as well as our body. "Bacteria and bacterial products can clearly have an effect on the brain and pathways leading to the brain," says Bienenstock. "There are quite a few papers now suggesting that you can influence behaviour, and that the microbiome has something to do with cortisol production, which are pretty hard-core, basic human reactions to stress and things like that."

In fact, Rook recently proposed that one reason depression is so prevalent in western countries is because people are no longer routinely exposed to organisms like M. vaccae during early life. The "hygiene hypothesis" was originally proposed to explain soaring rates of asthma and allergies, but Rook believes it could also be implicated in psychiatric disorders (Trends in Immunology, vol 29, p 150).

So could M. vaccae be used to make people happy? It is much harder to get approval to inject live bacteria into people with depression than those with terminal cancer, so Immodulon's next trial will be in people with prostate cancer. If there is a strong mood-boosting effect again, the company may focus more on its potential for treating depression. Ultimately, if the precise mechanism can be uncovered, it might be possible to develop drugs that mimic the bacterium's effect.

Read more: "Infectious moods: How bugs control your mind"

Linda Geddes is a New Scientist reporter based in London

Infectious moods: Bugs that cause bizarre behaviour

Sometimes it takes antibiotics, not a psychologist, to cure strange obsessions

Sammy Maloney was a healthy, outgoing 12-year-old, who played in the school band, and liked nothing better than to dump his backpack after school and hang out with his friends in Kennebunkport, Maine. Then, in 2002, Sammy's personality began to change. "The first thing I noticed was that he was walking around the backyard with his eyes closed," says Sammy's mother, Beth Maloney. "I asked him what he was doing, and he said he was memorising."

The next day, Sammy was again walking with his eyes closed and would only use the back door. Then he progressed to holding his breath while doing it, only wearing certain coloured clothes, and refusing to allow the windows to be opened, or the lights to be switched off. "Every single day was a new behaviour," says Beth. "We went from baseline to completely dysfunctional within a period of four to six weeks."

Sammy was diagnosed with obsessive compulsive disorder, and then Tourette's syndrome. When he continued to deteriorate, a friend suggested testing Sammy for streptococcus - a common childhood bacterial infection that usually causes no more than a sore throat. "By this point he was totally emaciated and he was covered with scabs from scratching himself," says Beth.

Sammy hadn't shown any signs of streptococcal infection, but it turned out he was infected. When doctors prescribed antibiotics, his symptoms began to improve. Within a few weeks he was playing board games with his brothers. "After six months of treatment, I knew that he would recover," says Beth.

Sammy remained on antibiotics for four years, as every time the dose was reduced he had a relapse. Now aged 20, Sammy has none of the compulsions that blighted his youth.

Madeline Cunningham at the University of Oklahoma in Oklahoma City says that, although extreme, Sammy's story isn't that unusual. She has spent years investigating behavioural disorders linked to childhood streptococcal infection, including Tourette's syndrome, an OCD-like disorder called PANDAS, and the movement disorder Syndenham's chorea, which is associated with tics and an inability to control emotions.

Cunningham has shown that, at least as far as Sydenham's chorea is concerned, antibodies against one group of streptococcal bacteria can bind to receptors in an area of the brain that controls movement. Here they mimic the effects of natural signalling molecules, triggering the release of the neurotransmitter dopamine, which may explain the tics and emotional problems experienced by children with the disorder (Autoimmunity, vol 39, p 21).

Not every child with PANDAS has similar antibodies, but for those that do antibiotics or drugs that suppress the immune system are effective treatments, says Cunningham. Preliminary evidence also links such antibodies to Tourette's syndrome.

Cunningham stresses that there is no evidence that vaccination can trigger disorders like PANDAS. "You're more likely to get this from not being immunised," she says.

Meanwhile, Betty Diamond of the Feinstein Institute for Medical Research in Manhasset, New York, has also shown that antibodies associated with the autoimmune disease lupus can get into the brain and kill neurons by binding to NMDA receptors. This might partly explain the mood changes and cognitive decline associated with the disease.

Mouse studies suggest how behaviour is affected depends on what makes the blood-brain barrier leak, as well as on the antibodies themselves. When the barrier is compromised by inflammation, lupus-related antibodies damage the hippocampus, impairing memory. When the barrier is breached by stress hormones (adrenaline), the antibodies damage the amygdala, making individuals more fearful. The results were presented at a meeting of the American Association of Immunologists in Baltimore in May last year.

"This could change the way we treat mental disorders forever," says Cunningham, who thinks antibodies influence the behaviour even of apparently healthy individuals. "Your immune system develops based on what organisms it sees, and it could be that your brain does too."

Diamond agrees: "We have tonnes of antibodies even when we don't have clinical disease. I'm sure that some of these are having an effect on the brain."

Read more: "Infectious moods: How bugs control your mind"

Infectious moods: The happiness injection