Gut and Brain Again

A long time ago, when I was an intern, I would drive into the hospital for ultra long shifts. Day went into night into the next day. You might be lucky to get one day off in a month. It's illegal now to work interns as much as we were worked, and I understand the sleep science behind the laws. But at the same time, you learn something about yourself and your patients in the long march over a day and a night and a day.

Bono says this song is about a hangover. I used to listen to it on repeat during that sleep-deprived drive into work for those long, long days. In A Little While. I would close my eyes on the elevator in the hospital and hear it playing in my head. Right now I am working a great deal on various projects and of course with my clinical practice. I hope to get a little bit of a break before too long…and have time to do more fun and interesting reading and blogging.

When we are born, we are colonized by the first generation of those eventual 100 trillion bacteria from nearly 1000 differenct species that makes up 90% of the cells of our body. These cells communicate with our brain and likely affect our behavior. The organisms help us to break down complex polysaccharides and they are critical to the normal development of the immune system. A relatively new paper reviews how they might influence anxiety and depression (1).

The mircobiome is influenced by age, diet, stress, metabolism, antibiotics, geography, and genetics. As regards stres reponse, mice lacking a microbiome have an exaggerated hypothalamic-pituitary-adrenal response to stress compared to mice normally colonized. The mircobiome seems to play a role in programming stress response from the very beginning. Stress will also increase intestinal permeability, which gives the bacteria of the microbiome greater access to communicate via inflammation and the enteric nervous system. Microbes can communicate with the human brain via various neurotransmitters, such as GABA, and there is also evidence that different gut bacteria have different effects on serotonin signalling in the central nervous sysem (at least in mice).

When pathogenic bacteria are introduced into the gut of mice, a robust central nervous system response is evident via the vagus nerve, followed by a systemic inflammatory response. Friendlier bacteria (such as lactobacilli) also elicit a central nervous system response, but not the systemic inflammation. Also in mice, certain neurons of the enteric nervous system change how excitable they are (or how easily they signal) depending upon the species of bacteria in the gut. Now repeated in many studies, the infection of mice with pathogenic bacteria increases anxiety-like behavior and treatment with friendly gut bacteria reverses the change in behavior. In some of these studies, changes in the production of nerve fertilizer (so to speak), brain-derived neurotrophic factor, matched the increases and decreases in anxiety-like behavior. The friendly bacteria are associated with greater nerve plasticity and repair, whereas the pathogenic bacteria showed the opposite.

In humans, there are few studies, and none in people diagnosed with clinical anxiety or depression. However, in a double-blind placebo controlled trial of probiotics given for 30 days (2), healthy volunteers who took the probiotic showed significantly less psychological distress than those who didn't. Another three week study showed the healthy volunteers with the most depression-like symptoms had significant improvement on a probiotic while those who took placebo had no benefit (3). There are also positive studies showing probiotics impacting anxiety symptoms in people with Chronic Fatigue Syndrome and undergoing cancer treatment.

Many questions remain that must be further studied. There are differences in how easily the gut microbiome is changed in different life periods, with childhood perhaps showing more amenability to change. In adults it is likely that fecal transplants and the introduction of chronic parasitic infection are the only practical way to permanently affect the microbiome. Childhood exopsure to antibiotics and probiotics may have different consequences than adult exposure to the same.


(2) Messaoudi, M. et al. (2011) Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut Microbes 2, 256–261

(3) Benton, D. et al. (2007) Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur. J. Clin. Nutr. 61, 355–361