Microbiota and the gut brain axis: When microbiology meets neurosciences

Chantilly, France

Scientists from around the world invited by Lallemand to its Second Scientific Exchange on the Gut-Brain Axis shared their latest findings about the implications of the gut and the microbiota in response to stress and anxiety. This topic was a rare occasion to gather in the same room neurobiologists, behavioural experts, microbiologists gastroenterologists, but also animal nutritionists. The communication between the brain and the gut, which is sometimes called ‘the second brain’, is a bidirectional dialogue that co-ordinates brain and gut functions.

However, if the relationship between the brain and the gut, which harbours 70 per cent of our nervous cells (the enteric nervous system), has been known for a long time, Dr Theodorou from INRA in Toulouse, who chaired the symposium, explained in her introduction that new players have emerged along the way: the immune system (also largely represented in the digestive tract since 60-70 per cent of our immune cells are associated with our gut), and, more recently, the microbiota, which has certainly been overlooked until now.

Our guts harbour around 10 times more bacteria than the number of cells in our body, and 100 times more genes than our own genome. If several animal studies and hypothesis around digestive pathologies prove the implication of the microbiota in the gut-brain cross-talk, or Gut-Brain Axis, Dr Theodorou admitted that the exact mechanisms involved are still a ‘black box’ needing further investigations. Exciting data were presented about the great potential of probiotics to modulate the gut-brain axis and, for example, to impact our response to stress and anxiety.

The chicken and egg dilemma

Some scientists have recently noticed that, in certain behavioural conditions such as autism, anxiety or depression, the microbiota is altered, and they are trying to link the condition to a particular microbiota profile. But is it the microbiota which determines the behaviour or the other way round?

Prof. Collins, from Mc Master University, in Canada, gave another approach to this chicken and egg dilemma by showing that stress, by altering the gut environment, can alter the microbiota. In an animal model for anxiety and depression, his team showed how behavioral changes or stress alters the gut microbiota and that a particular neurotransmitter involved in the stress-response (the corticotrophin releasing hormone – CRH), could play a role by altering the gut physiology and hence the habitat of the microbiota.

Several studies presented during the meeting showed that an alteration of the microbiota can affect the behaviour of animals or modify the stress response and visceral sensitivity. In particular, Prof C Collins presented some microbiota transfer experiments in mice which lead to a ‘behavioral transfer’.

The gut-brain axis is essential for maintaining intestinal homeostasis and wellness, and we now know that the disruptions of this axis could be implicated in certain pathologies in human, ranging from functional and inflammatory intestinal illnesses to behavioral disturbances, particularly those recently associated with intestinal dysbiosis.

One of the questions raised from the tri-party cross-talk is whether we can act on the gut-brain axis by rebalancing the gut microbiotia with probiotics? Prof John Cryan, from Cork University, in Ireland, brought the neurobiologist point of view. He recognised that it is not until very recently that neurobiologists have started to consider the role of the microbiota and he presented several animal studies that could be considered as real proof of concept of the role of the microbiota on the stress response. What he wanted to know was whether probiotic could affect the stress response in adults, and also affect the cognitive behaviour. He presented some recent works showing the positive effect on stress and anxiety behaviour in rodents of a strain of L rhamnosus, effect which was accompanied by improved cognitive performance.

Knowing that irritable bowel syndrome has a slight effect on learning memory, it could be interesting to see if the modulation of the gut microflora could also enhance cognitive performance in addition to stress response in human. Professor Didier Desor, an expert in cognitive science from Nancy University, in France showed that a particular probiotic formula (L. helveticus R052 and B. longum R175 – Probio’Stick) displays anxiolytic-like activity in rats.

In humans, two previously published studies have shown that this probiotic was able to reduce physiological symptoms associated with chronic stress, in particular abdominal pain and nausea, reduce signs of anxiety and depression, using different psychological tests and a biomarker for stress (cortisol). In Montreal, Professor Guy Rousseau, tested the same formulation on a rat model of post-myocardia infarction depression, a condition associated with 20 per cent mortality in human not only could he show a preventive effect against depressive behaviour, but he also observed an effect of the probiotic at brain-level in areas of the brain associated with mood and behaviour (lymbic and hippocampic areas), the tendency of brain cells to enter into apoptosis (also named programmed cell death, a form of cellular suicide) was decreased thanks to the probiotics.

Looking into the ‘black box’ Dr Ait-Belgnaoui, presented a new study conducted at INRA in Toulouse, which aimed at further investigating the ‘black box’ by looking at the effect the probiotic could have on brain cells. Using a mouse model of chronic psychological stress, she showed that the stress-targeting probiotic formula had the ability to decrease the neuroendocrine response to stress, and prevented the stress-induced activation of certain neurons in some areas of the brain which are involved in stress response. In another region of the brain, the probiotic normalised neuronal activity which is normally depressed by chronic stress. It thus appeared that the probiotic was able to restore the negative response associated with chronic stress at brain level.

In the recent study presented by Prof Cryan with L rhamnosus in mouse, the researchers also demonstrated that the probiotic had an effect on the expression of GABA receptors (GABA is the main inhibitory neurotransmitter) at brain level, and that the probiotic effect was mediated via the vagal nerve. If all these recent works clearly illustrate the fact that the probiotic effect on the digestive microbiota is reflected at brain level, most of the black box still remains a mystery. However, these novel findings are very exciting and open a wealth of opportunities in the management of pathologies linked to a dysfunctionning gut-brain axis, such as IBS.

EP News Bureau — Mumbai