#sadmice

Over the last couple of months I’ve discussed the relationship between the bacteria in your gut and the brain, the bacteria’s influence on neurodevelopment, and how there’s really not as much bacteria in our bodies as we once thought. So how are researchers taking advantage of this interplay between bacteria and brain? Enter psychobiotics. This term has been coined to describe a class of probiotics that have the ability to modulate the gut-brain axis, imparting a beneficial effect on mood, and cognition. The idea here is to eventually employ these psychotropic bacteria in clinical settings to improve psychiatric symptoms in individuals. Now is this in the realm of possibility, or simply too good to be true? Let’s talk about that.

Probiotics are live microorganisms that, when administered in adequate amounts, confer a beneficial effect on the health of the host. Administering bacteria to provide health benefits is not a new concept and you’ve probably seen a variety of probiotics lining the shelves of your local grocery store. These products are highly regulated and have a number of characteristics. An ingested probiotic needs to be non-pathogenic, it must be able to survive in the human digestive system, and it needs to compete with indigenous bacteria and effectively colonize the intestinal tract.

The gut-brain axis is a bidirectional system of communication between the gut and the brain. The bacteria can act on a number of pathways such as tryptophan metabolism, metabolite production, and the vagus nerve, to exert their influence on the brain. (For a more in depth discussion on the gut-brain axis, check out my previous post). This pathway connecting the gut to the brain is the target for these so-called psychobiotics. By modulating the gut-brain axis, perhaps it is in turn possible to modulate brain function.

Several probiotics have been shown to impart beneficial effects to improve symptoms of anxiety and depression. For example, administration of Lactobacillus rhamnosus has been shown to reduce depression-related behaviour in mice, Bifidobacterium longum has had the effect of reducing anxiety-like behaviour in rats, and Bacteroids fragilis has even alleviated autism-like behaviour in mice models.

A particularly interesting example of a psychobiotic involves Lactobacillus plantarum. In a study published earlier this year in the journal Brain Research, researchers investigated the psychotropic effects of this bacterium. Sticking with the rodent theme, mice were subjected to early life stress in the form of maternal separation. The pups were pried away from their mothers between 2 and 14 days after birth. As you would expect, this is particularly stressful for the newborn pups. Maternal separation (MS) is frequently used to induce early life stress in mice and to investigate the pathophysiology of stress-related disorders.

Figure 1: To induce early life stress, newborn mice were separated from their mothers for 3 hours a day. This was done between 2 days and 14 days after birth.

The probiotic was administered to the mice for 4 weeks after which a series of tests were performed to evaluate the pychotropic potential of the bacteria.

Mice subjected to maternal stress often show a number of behavioural abnormalities including increased anxiety-like behaviour and increased depression-like behaviour. Chronic administration of the probiotic actually caused distinct alterations to behaviour of the mice. Mice had reduced depression-like behaviour and actually demonstrated increased locomotive behaviour when compared to control mice.

So what is behind this positive effect on behaviour? Although not entirely clear, the researchers have proposed a couple of possibilities.

Mice inflicted with early life stress had significant increases in serum IL-6 levels and decreases in IL-10 levels. Alterations to these cytokines have previously been implicated with stress-related disorders in humans. In a clinical study, patients with major depression demonstrated a higher ratio of IL-6 to IL-10, as well as a decrease in serum IL-10 levels, compared to patients without major depression. Treatment of the mice with the probiotic resulted in a reduction of serum IL-6 levels. Indeed in preclinical animal studies, reductions in this cytokine have been associated with reductions in depression-like behaviour.

Figure 2: The mice that underwent early life stress were split into two groups: a control group that was fed a saline solution and an experimental group that was fed the probiotic. After administration of the probiotic the mice in the experimental group were found to have decreased depression-like behaviour.

Furthermore, mice that were administered the probiotic had increased concentration of dopamine in their prefrontal cortex. The prefrontal cortex is an intricate structure that has been associated with stress responses, decision-making, and personality (you may remember the case of Phineas Gage). The researchers suggest that the abnormal behaviour in the early-stress mice may be in part due to alterations to dopamine in the prefrontal cortex. Thus by administering the probiotic, dopaminergic activity is increased, and behaviour is normalized.

This psychobiotic looks like the real deal right?

Well, it’s not that simple  Even with promising results like this, it is very difficult to translate from animal models to the clinic, even more so when the specific mechanism of action has yet to be resolved.  

Even when studies are done with humans, we run into some difficulties. Take this study for example. A multi-species probiotic was found to reduce negative thoughts related to sad mood in healthy participants. But we do need to consider a number of other factors that may have contributed to this. The researchers did not control diet during the trial, including the consumption of other probiotics. Similarly, it is likely that other aspects of the participants’ lifestyles or environment were playing a part.

So now we arrive at back at the original question. Do these psychotropic bacteria have a realistic capacity to positively influence cognition?

Maybe.

I know that’s probably not the answer you wanted to hear, but it is the most accurate one. This entire field is still in its infancy and if you’ve been following my blog, you know there is still so much we need to learn. The bacteria are having an impact on brain and behaviour – we just don’t know exactly how. Obviously more research needs to be done to elucidate these mechanisms. And more research is required in clinically diagnosed patients. This is a fascinating field of study that seemingly holds a lot of promise. Whether we’re going to start seeing psychobiotics along side conventional probiotics on store shelves, only time will tell.

- Babar

For more: http://www.sciencedirect.com/science/article/pii/S0006899315008628