A curious connection

Dear Physiologist,

Have you ever heard of a connection between the intestinal bacteria and the brain? We are aware of the benefits of these bacteria in producing some important nutraceuticals like vitamins, but now the nature of the flora is also considered to be very important. Lack of certain flora and their products may lead to diseases. In normal people, there seems to a balance among various types of bacteria in the gut. In the event of an imbalance, disease process may be triggered. Let seek some experimental proof.

Patients suffering from depression often show suicidal tendencies, melancholia and psychosis. Mice delivered and reared in totally sterile and germ-free conditions exhibit a preference for isolation and show sparse social interaction. Like the patients with depression, their hypothalamo-pituitary-adrenal axis is abnormal showing increased response to stress, as judged by the increased secretion of cortisol and adrenaline. But if they are fed with feces of normal mice from the birth, hyper activity of HPA seems to be largely ameliorated. Another defect found in the germ-free mice is the underdevelopment of cortex and hippocampus along with defects in memory. Brain-derived neurotrophic factor is deficient in these areas. How do we connect this with the lack of bacteria in the gut? Gut organisms produce GABA, ACh and noradrenaline. They regulate the metabolism of tryptophan and thereby the production of serotonin. A gut deficient in bacteria may fail to generate the neurotransmitters necessary for normal brain development.

Human studies have proved equally interesting! Prolonged stress leads to the breakdown of the protective barrier of the gut allowing the gut bacteria to escape into the circulation. An inflammatory response thus triggered may result in excess production of inflammatory interleukins. In a number of studies on patients suffering from major depression, elevated levels of IL-6 were found. When such patients were treated with fluoxetine, IL-10 levels started increasing. While IL-6 is pro-inflammatory, IL-10 is anti-inflammatory! Does this mean that depression can be cured by supplying appropriate bacteria to the gut? A study looking at the bacteria in fecal samples of depressed patients and normal individuals showed significant differences in the types of bacteria. They studied the DNA isolated from the feces, to ensure that all the bacteria are detected. What happens if you feed probiotics (useful bacteria) to normal individuals? Will their moods change? In a few randomized double blind placebo controlled studies conducted on normal individuals, those receiving probiotics had reduced anger, hostility and psychological distress. Many of them expressed a sense of happiness! Making use of this peculiar line of communication between gut bacteria and brain may pave the way for probiotic treatment of disease!

Dr. J. Prakasa Rao
Professor of Physiology (Rtd)