First study in humans to demonstrate impact of probiotics on brain responses to an emotional reactivity task — online press conference at 2nd World Summit “Gut Microbiota For Health” held tomorrow

(25 February 2013) The intake of probiotics has a measurable effect on brain areas that are associated with reactions to an emotional attention task. This has, for the first time, been demonstrated in humans by a study with 45 test persons, carried out by Dr Kirsten Tillisch and the team of Professor Emeran Mayer at the University of California, Los Angeles, USA. The interplay between the gut’s own nervous system, the microbiota, and the brain turns out to be an increasingly promising area of research, offering a huge potential for new therapeutic approaches to intestinal and possibly brain-related disorders. This is one of the topics presented at the 2nd World Summit “Gut Microbiota For Health” in Madrid, Spain. Since 24 February 2013, internationally leading experts have been discussing the latest advances in gut microbiota research and its impact on health.

It has long been recognised that functional gastrointestinal disorders are often accompanied by psychological symptoms, such as anxiety or depression, and that anxiety is one of the best predictors of perceived symptom severity. On the other hand, feelings of well-being and content are generally associated with eating a nice meal. The reason for the close link between emotional feelings and gut function is related to a variety of bidirectional communication channels via which the gut and brain maintain a permanent exchange of messages that medical research is busy trying to decode. But recently it has become clear that a third player is part of the game — the gut microbiota. Due to the vast neuronal network that is harboured by the gut wall and connected with the brain, intestinal bacteria and their metabolites not only can influence gut functions, such as motility and secretion, but, based on preclinical studies, may even influence emotional behaviours.

Another road through which gut bacteria may get in contact with brain circuits is the blood stream. Unsurprisingly, based on several recent publications on rodent studies, the hopes for improved future treatments of intestinal and possibly even psychiatric diseases are high. However, many of the details of this utterly complex interplay demonstrated in animal models remain to be investigated before research results can be translated into possible clinical applications.

Probiotics and the brain

One important step towards this goal has been made by Prof. Mayer’s team and the lead investigator of the study, Dr Kirsten Tillisch. The scientists wanted to know whether probiotics might affect evoked brain responses, in a measurable way, through change of the gut microbial composition. Prof. Mayer’s study is the first and, so far, only one of this kind that has been carried out in humans, as other investigations in this vein have been restricted to animals, mostly mice. The trial group consisted of 45 women between 18 and 50 years of age without any physical or psychiatric diagnoses or symptoms. They were randomly assigned to three test groups. Over a period of four weeks, the participants of the first group consumed 125 grams of a fermented milk product with probiotics twice a day, while the second group took in the same amount of an indistinguishable control product. The third group received no treatment.

At the end of the trial period, the researchers wanted to measure the potential impact the manipulation of the gut microbiota might have had on the brain. To this end, the participants underwent a validated Emotional Reactivity Task (ERT) that consisted of viewing faces expressing negative emotions, such as fear and anger, which results in the engagement of task-related brain circuits (including sensory and affective brain regions), without inducing any emotions in the test subject. Viewing emotionally neutral shapes served as a control. While the women performed the test, their brains were being scanned, using functional magnetic resonance imaging — which makes activity-related regional blood flow changes in the brain visible — in order 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. “Thus, 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’). This means that processes that had already been observed before in rodents, may occur similarly in humans. Such microbiota-related effects on brain circuits may play a role in the beneficial effect of probiotics on some GI symptoms in functional disorders,” says Prof. Mayer. 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.”

Do antibiotics affect brain development?

Taken together with the results of several trials that showed significant behavioural changes in mice in connection with gut microbiota manipulations, the importance of these findings for assessing the role of the gut-brain-microbiota triangle is considerable.

According to Prof. Mayer, the most intriguing observations, within the research area as a whole, are that the gut microbiota may have an effect on brain development and that antibiotics may change gut-to-brain signalling. This impact has been demonstrated in mice that are germ-free (without gut microbes) — an extreme form of a disturbed microbiota, so to speak.

“Given the widespread use of antibiotics in neonatal intensive care units and in paediatrics for common diseases, such as sinusitis, bronchitis and respiratory tract infections, it is conceivable that the dysbiosis resulting from these interventions may affect brain development in children. What we urgently need are studies exploring these possible relations between antibiotic use, dysbiosis, and cognitive and emotional conditions in children.”

About the Gut Microbiota For Health Experts Exchange website

The Experts Exchange, provided by the Gut Microbiota & Health Section of ESNM, is an online platform for health-care professionals, scientists, and other people interested in the field. Thanks to being an open, independent and participatory medium, this digital service enables a scientific debate in the field of gut microbiota.

Connected to, the Twitter account @GMFHx, animated by experts, for experts from the medical and scientific community, actively contributes to the online exchanges about the gut microbiota. Follow @GMFHx on Twitter. Join the event on #GMFH2013

About the Gut Microbiota & Health Section of ESNM

ESNM stands for the European Society of Neurogastroenterology and Motility, a member of United European Gastroenterology (UEG). The mission of the ESNM is to defend the interests of all professionals in Europe involved in the study of neurobiology and pathophysiology of gastrointestinal function. The Gut Microbiota & Health Section was set up to increase recognition of the links between the gut microbiota and human health, to spread knowledge and to raise interest in the subject. The Gut Microbiota & Health Section is open to professionals, researchers, and practitioners from all fields related to gut microbiota and health.

About the AGA

The American Gastroenterological Association is the trusted voice of the GI community. Founded in 1897, the AGA has grown to include more than 16,000 members from around the globe who are involved in all aspects of the science, practice and advancement of gastroenterology. The AGA Institute administers the practice, research and educational programmes of the organisation.

About Danone Dairy and Gut Microbiota For Health

Danone’s conviction is that food plays an essential role in human health namely through the impact that gut microbiota may have on health. That is why Danone Dairy supports the Gut Microbiota For Health World Summit and Experts Exchange web platform with the aim to encourage research and increase knowledge in this promising area, in line with its mission to “bring health through food to as many people as possible”.

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