From the time we are born, millions of bacteria set up home in and on our body with the largest contingent living in the coils of our intestines. For every human cell intrinsic to our body we have about 10 resident bacteria, most of them harmless, many useful and only in a tiny number of cases, some pathogenic. A growing body of research has shown that disorders in the internal ecosystem of our gut bacteria or microbiota are related to many health problems. These bacteria exert an influence on our health and well being just like the genes we inherit from our parent and scientists say the microbiome, defined as all the microorganisms inhabiting the human body, is the next frontier in understanding the human body.

There is evidence of interactions between the intestinal microbiota, the gut, and the central nervous system (CNS) in what is recognized as the microbiome–gut–brain axis. Studies in rodents have implicated alterations in this axis for functional bowel disorders, including irritable bowel syndrome. In addition, it has been shown that modification of the microbiota in mice affects the hypothalamic–pituitary–adrenal (HPA) axis which has traditionally been seen as the body’s “stress system”, and which ultimately controls levels of cortisol and other important stress related hormones.

To understand the role of bacteria in the bidirectional communication of the gut–brain axis, Bravo et al1. carried out a series of behavioural tests relevant to anxiety and depression on mice fed probiotics, live microorganisms which are thought to confer health benefits on the host. Mice were fed a diet containing a probiotic, Lactobacillus rhamnosus (JB-1), or broth without probiotics for 28 days and then screened using the elevated maze plus test, which is a model for testing rodent anxiety. The setting consists of a plus-shaped apparatus with two open and two enclosed arms and is based on a rodents’ aversion of open spaces. Anxiety reduction in the plus-maze is indicated by an increase in the proportion of time the mice spends in the open arms

The test results, published in the journal Proceedings of the National Academy of Science (PNAS) in 2011, clearly demonstrated a change in behavioural and physiological responses in normal, healthy mice induced by modifying the gut microorganisms using the probiotic, L. rhamnosus (JB-1). Probiotic-fed mice were less anxious and displayed antidepressant-like behaviour in comparison with broth-fed controls. They also found that feeding the mice probiotic reduced the stress-induced elevation in corticosterone concentration, a hormone which regulates immune reactions and stress response in rodents.

Another interesting observation was an increase in the number of GABA receptors in the brain of probiotic-fed mice. GABA, a common chemical messenger in the brain, functions to control fear and anxiety and GABA receptors are crucial for maintenance of normal behaviour. The authors speculate that the increase in the number of receptors in the brain of probiotic-fed mice suggest that the bacteria could have promoted an adaptive advantage over broth-fed animals in terms of interaction with stressful situations. L. rhamnosus (JB-1)-fed animals had also exhibited an enhanced memory to an aversive situation in comparison with broth-fed mice.

These results raised the intriguing question – can emotional behaviour in humans be altered by gut microbiota? University of California Los Angles, researchers now have evidence that women who regularly consumed probiotics in yogurt exhibited measurable effects on brain areas associated with reactions to an emotional attention task.

Healthy women were randomly assigned to three groups – a group of 12 women were given 125 gms of fermented milk product with probiotics (Bacillus lactis CNCM I-2494, Lactobacillus bulgaricus, Streptococcus thermophiles, and Lactobacillus lactis), the second group of 11 were given non-fermented milk products, twice daily for 4 weeks & there was no intervention in the last group of 13 women2.

The participants underwent a validated Emotional Reactivity Task (ERT). This consisted of test subjects viewing faces expressing negative emotions, such as fear and anger while their brains were being scanned using functional MRI – to detect and measure task-corresponding neuronal activities. The results showed a reduced response to the task in the women who had consumed probiotics, compared to the two other groups.

“We could prove that regular intake of a probiotic can affect, in a traceable way, regions in the human brain concerned with the central processing and modulation of afferent signals from the gut (‘visceral sensations’)” said Prof. Mayer3, the lead investigator of the study published recently in the journal, Gastroenterology. Nevertheless, he cautions against premature conclusions: “We have to be extremely careful to extrapolate from these studies to complex human emotions, such as anxiety and depression. At the moment, there is no convincing evidence that the ingestion of any probiotic has an anti-depressant or anxiolytic (anti-anxiety) effect in humans.”

Prof Mayer added4 “There are studies showing that what we eat can alter the composition and products of the gut flora — in particular, that people with high-vegetable, fibre-based diets have a different composition of their microbiota, or gut environment, than people who eat the more typical Western diet that is high in fat and carbohydrates. Now we know that this has an effect not only on the metabolism but also affects brain function.”

The most intriguing question raised by the study – Can repeated courses of antibiotics, which eliminates the gut microbiota, affect the brain? Antibiotics are used extensively in neonatal intensive care units and in paediatrics for common diseases, such as sinusitis, bronchitis and respiratory tract infections. Such suppression of the normal microbiota may have long-term consequences on brain development.

According to Prof. Mayer ”What we urgently need are studies exploring these possible relations between antibiotic use, dysbiosis, and cognitive and emotional conditions in children.”


References

  1. Bravo JA, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. PNAS 2011;108 (38):16050-16055
  2. Tillisch K, et al. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology 2013;144(7):1394-1401
  3. Pierre-Yves Arnoux (2013, Feb 20) Gut feeling: Can the microbiota talk to the brain? Gut Microbiota for Health
  4. Study shows changing gut bacteria through diet affects brain function (2013, May 29) SciTechDaily
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