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Breakthrough Research Reveals Role Gut Bacteria May Play in Obesity-related Anxiety and Depression

A connection between obesity, anxiety, and depression has long been suspected by physicians and medical researchers, but the exact reason for the connection in human beings has yet to be proven. However, researchers at Joslin Diabetes Center have released a new animal study that is thought to give a better understanding of the connection between diet, gut bacteria, and mental wellness.

The Joslin Diabetes Center study focuses on Microbiome research and the intriguing subset of research into the growing connections that link gut bacteria and the brain. Research in this area focuses on the neurochemical effects stemming from the unique makeup of the gut microbiome and the connection to mental illness caused by everything from PTSD to depression.

The new study results indicated that when mice were fed a high-fat diet, they exhibited substantially greater depressive behaviors until microbiome-altering antibiotics returned their behavior back to normal.

It’s been long established by physicians that sufferers of type 2 diabetes and obesity all too often suffer with depression and anxiety at an exponentially higher rate than the rest of the general population. The direct cause of these debilitating psychological effects, however, has yet to be proven. However, many physicians and medical researchers have opined that it’s connected not only to diabetes, but to diet and excess weight.

There have been a handful of animal studies that have indicated that anxiety and or stress-related behaviors of mice can be reduced by changes in the gut microbiome via different bacteria. The Joslin research study was designed to examine how mice on high-fat diets react to microbiome alterations in hopes of proving that their moods can be altered.

Joslin Diabetes Center has already conducted prior research that proved the onset of disease could be modulated by specific changes in gut bacteria of mice both fed a high-fat diet and bred to develop various metabolic diseases such as diabetes. This new Joslin study was designed to specifically examine the influence of mood affected by high-fat diets and if microbiome alterations could be used to moderate mood.

The Joslin study showed at first, mice on a high-fat diet exhibited more clinical signs of depression and anxiety than control mice fed a normal diet. Then, researches administered antibiotics to those mice on a high-fat diet and saw their behaviors return to normal.

This was tested by giving the mice on high-fat diets two different broad antibiotics: vancomycin, with the goal of destroying gram-positive gut bacteria, and metronidazole, which is known to kill anaerobes. The researchers found that both antibiotics appeared to reverse any dietary-induced negative behavior, which improved insulin-signaling in the brain disrupted by the high-fat diet.

The researchers tested several different microbiomes by transferring gut bacteria from the test mice into mice genetically engineered to have absolutely no natural gut bacteria of their own. Mice that had transplanted gut bacteria exhibited the exact same behavior of the donor mice.

The Joslin study zeroed in on specific brain mechanisms that were affected by these microbiome alterations. The researchers found compelling observational evidence that many brain changes in the mice were clearly brought on by the high-fat diet and were reversed when the antibiotics were administered.

"We demonstrated that, just like other tissues of the body, these areas of the brain become insulin resistant in mice on high-fat diets," says C. Ronald Kahn, senior author on the new Joslin study. He went on to say…

"And this response to the high fat is partly, and in some cases, almost completely reversed by putting the animals [on] antibiotics. Again, the response is transferrable when you transfer the gut microbiome from mice on a high-fat diet to germ-free mice. So, the insulin resistance in the brain is mediated at least in part by factors coming from the microbiome."

The Joslin study did not specifically identify which bacteria triggered neurochemical changes or what physiological mechanism in the test mice may have generated improved mood. Yet, it's an exciting first step and yet another piece of strong observational evidence suggesting the bacteria in our gut could have a more profound effect on human mental well-being than medical science has ever believed.

C. Ronald Kahn, however, opined in this new Joslin study that antibiotics can be used to alter a broad spectrum of gut bacteria, but would never be an end result for human treatments. More research is needed…

"Antibiotics are blunt tools that change many bacteria in very dramatic ways," says Kahn. "Going forward, we want to get a more sophisticated understanding about which bacteria contribute to insulin resistance in the brain and in other tissues. If we could modify those bacteria, either by putting in more beneficial bacteria or reducing the number of harmful bacteria, that might be a way to see improved behavior."

The study was published in the journal Molecular Psychiatry. Source: Joslin Diabetes Center via EurekAlert

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