Thursday, March 23, 2017

Bugs To Drugs: Can Probiotics Treat Depression?

Depression is a debilitating mental illness that affects up to 15 million Americans in the US alone, yet we are far from understanding the root cause. Multiple genes have been associated with depression, but whether these genes produce symptoms depends on the individual’s environment. New research is showing that one of the biggest environmental factors impinging on mental health comes from within.

Our body is home to trillions of microscopic creatures, mostly bacteria, which are collectively referred to as our microbiota. As unsettling as that may sound, these microbes are not necessarily the kind we want to evict from our body. The bacteria dwelling within our gut serve many important functions; for example, they help digestion, produce vitamins, and keep other types of microbes that cause disease at bay.

Our microbial inhabitants bring countless additional genes into our body called the “microbiome.” These microbial genes can be considered an extension of our own DNA – a so-called “second genome.” In other words, your body is not only influenced by the genes in your DNA, but it can also be affected by genes carried by your microbiota. These microbial genes not only affect physical health, but may also alter your mood and personality.

It is convenient to refer to species of our microbiota as "good" or "bad", but in reality they are neither. There are bacteria that can cause serious disease, like C-diff, but usually only after the microbiota has been disrupted (e.g. after prolonged antibiotic treatment). Likewise, "good" bacteria like E. coli can cause life-threatening disease under the right circumstances.  
Our microbiota help produce surprising amounts of neurotransmitters – chemicals that function in brain signaling. When laboratories produce “germ-free” mice by raising them in sterile environments, the mice exhibit strange neurological issues. Lacking their gut microbiota, germ-free mice do not respond to stress properly. These studies have given rise to the concept of the “gut-brain” axis, a conduit of biochemical communication between these organ systems. Such an axis exists in people too, as researchers have noted a strong correlation between intestinal problems and mental illness. For example, anxiety and depressive disorders are associated with both irritable bowel syndrome and ulcerative colitis.

A study by Ioana A. Marin and colleagues at the University of Virginia, published on March 7, 2017 in Scientific Reports, provides new evidence that intestinal bacteria influence mental disorders such as depression. In this experiment, mice were subjected to unpredictable chronic mild stress (UCMS), which involves strobe lights, irritating noise, cage tilting, and crowded conditions. Kind of like being shoved into noxious nightclubs against your will at random times throughout the day.

Unlike Disco Mickey, laboratory mice become stressed out when subjected to stimuli that resemble your average nightclub.
Over time, mice subjected to UCMS begin to show symptoms that resemble depression in humans. The researchers look for “despair behavior,” which can be detected in a number of ways. In this study, the mice were placed in a tub of water to evaluate despair behavior. Unstressed mice quickly swam to a platform and escaped, but the stressed mice did not make a strong effort to escape and had to be rescued from the tub.

The researchers then compared what the intestinal microbiome looked like in stressed versus unstressed mice. The different species of bacteria comprising the microbiota can be determined by sequencing the DNA in mouse droppings. Each species has a signature DNA sequence that serves as an identifier for that type of bacteria.

The results showed that stress altered the mouse microbiome by reducing a type of bacteria called Lactobacillus. It might have occurred to you that stress could have simply changed the eating habits of the mice, which in turn would affect the composition of the microbiome, but the researchers did not observe any change in eating habits or weight of the stressed mice. Furthermore, when they administered Lactobacillus as a probiotic, the symptoms of depression improved.

Why would stress cause changes in the microbiome? No one knows for sure, but this could be a result of altered brain chemistry making the gut less hospitable to some bacteria. Researchers also noted that intestinal physiology was altered in the stressed animals, which could have played a role in microbiota changes.

When someone consumes a probiotic they are ingesting live bacteria. That concept should no longer gross you out. Probiotics include the so-called "good" bacteria that have been shown to confer health benefits in some studies. These bacteria can be delivered into your body in numerous ways, including food (like yogurt) or pills.  
Does this mean you should rush out to purchase probiotics to battle depression? There are important caveats to studies like this that should be considered. The study was performed in a mouse model of depression, which may not fully represent the condition in humans. The microbiome of controlled laboratory animals is more uniform than humans, who tend to have vastly different bacteria in their guts depending on such things as diet, geography, illness, and age.

However, a 2016 meta-analysis (a study of studies) concluded that “probiotics were associated with a significant reduction in depression [in humans], underscoring the need for additional research on this potential preventive strategy for depression.” While that sounds encouraging, we are far from understanding how certain bacteria may ameliorate depression and whether this affect holds up in diverse patient populations. Probiotics certainly should not replace the more rigorously established treatments for depression recommended by health professionals.

Bill Sullivan is a professor at the Indiana University School of Medicine. Follow him on Twitter @wjsullivan.