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Microbiota, the intestinal revolution. © INRA

Microbiota, the intestinal revolution

The dialogue between intestine and brain

More than 200 million neurons are connected to the human intestine, a number that rivals that of the brain. The idea that the brain and intestines communicate with each other is nothing new; scientists have been looking at the question for more than half a century. But the idea that this communication is a two-way street, and that the intestines also send messages to the brain, is a more recent one. Little by little, research is showing how the human microbiota is an integral part of this dialogue. Anxiety, depression, autism, mood… intestinal bacteria shape behaviour, regulate emotional response, and have a role to play in ailments of the nervous system. What are the mechanisms of this communication? How can probiotics be used to improve it? More than ever, INRA researchers are lending their ears to this dialogue between the gut and the brain.

Updated on 04/25/2017
Published on 02/16/2017

Lactobacillus lines the stomach mucosa of mice. © INRA, ABRAMS CD.
Lactobacillus lines the stomach mucosa of mice © INRA, ABRAMS CD.

Lactic acid bacteria to combat stress?

It is now a well-known fact that the brain, gut and microbiota are in constant dialogue with each other. For more than a decade, INRA researchers have been studying the role of diet in digestive inflammatory phenomena. Recently, they discovered that the intake of the probiotic bacteria Lactobacillus farciminis (a lactic acid bacteria) can significantly reduce stress in rats. How does it work? This probiotic renders the intestinal wall less permeable, thereby limiting the capacity of lipopolysaccharides in the intestines to cross over into the bloodstream. Lipopolysaccharides are known to induce neuro-inflammations in the brain that exacerbate stress. Reducing their mobility would therefore have an anti-stress effect. Could dairy products be the answer to what ails 21st-century man?

 

Stress response: the role of the microbiota

Behavioural test to compare and contrast anxiety levels in rodents with controlled microbiota.. © Laurent NAUDON - Inra, NAUDON Laurent
Behavioural test to compare and contrast anxiety levels in rodents with controlled microbiota. © Laurent NAUDON - Inra, NAUDON Laurent

The relationship between anxiety and the microbiota has been studied at length by INRA researchers. They examined a species of rats known for being genetically prone to stress by comparing a group born and raised in a microbiological sterile bubble (rats without microbiota, or “axenic”) with a group of rats from the same species born and raised in a non-sterile bubble (rats with a microbiota, or “conventional”). Both groups were then subjected to a very anxiety-inducing situation:  the animals were placed in a corner of a rectangular arena brightly lit in the centre. They reacted as follows. The rats devoid of a microbiota went to greater pains than their conventional counterparts to avoid the centre of the arena, which shows that they were more anxious.  Blood analyses of corticosterone levels, the stress hormone in rodents, confirmed that, all things being genetically equal, axenic rats are more susceptible to stress than conventional rats. The mechanisms governing this relationship between microbiota and stress are still the subject of study. In the meantime, “a stomach in knots” is still a telling phrase.

 

Separation of mother and newborn:new stress is born

When a baby is born prematurely, he or she must be separated from the mother to receive appropriate care. This separation from the mother and premature birth are at the root of dysbiosis, and increase the risk of developing psychiatric disorders. According to a scientific hypothesis, the microbiota may play a role in the onset of behavioural disorders. Studies carried out at INRA on axenic rats colonised at birth with a reconstituted microbiota from premature babies have shown that this microbiota, associated with separation from the mother, may engender motor hyperactivity in adult rats. Could this hyperactivity be a direct consequence of a modified microbiota? This is probably the case, since the hyperactivity is correlated with bacteria. Researchers showed that a microbiota reconstituted from three key types of bacteria can modify the behaviour of a rat, making it hyperactive. It remains to be determined which bacteria (alone or in association) within the microbiota come into play in this hyperactivity and how to reverse its effects. The findings of these studies on human health are very promising.

Microbiota and autism: a relationship under investigation

There is no doubt about it: autism is on the rise. The portion of the population affected by autism has been increasing uncontrollably since the 1960s. According to the latest figures, one baby out of 64 born in the United States will become autistic:  a disturbing and dramatic situation. But now we know that some 50% of autistic people suffer from major gastro-intestinal disorders that may well be treatable by remodelling the microbiota. Based on this observation, INRA researchers have teamed up with the Henri Mondor hospital in Créteil and the Nantes university hospital to launch studies on the role of the microbiota in autistic patients. The overall goal is to see if patients whose microbiota have been analysed correspond to the psychiatric diagnoses of people who suffer from autism, schizophrenia, treatment-resistant depression or bipolar disorders.

Microbiota and the nose

Brown rat from the Neurobiology of Olfaction Laboratory. Scientists observe and study behavioural response relative to certain olfactory stimuli.. © INRA, Bertrand Nicolas
Brown rat from the Neurobiology of Olfaction Laboratory. Scientists observe and study behavioural response relative to certain olfactory stimuli. © INRA, Bertrand Nicolas

Does the microbiota influence the sense of smell and shape dietary behaviour? In an unprecedented study, INRA researchers looked at how the microorganisms that populate our digestive tract and nose influence olfaction in mice. They found that in axenic mice, the olfactory system still functions, but in a different way. Surprisingly, they found that the olfactory neurons of axenic animals activate faster and with greater intensity. The microbiota therefore has a significant impact on the first stage of detecting odours. Our sense of smell is a key factor in the process of eating, and these results indicate that food preferences may vary based on the microbiota. It remains to be determined whether olfactory preferences vary according to the nature of the microbiota. These studies are opening up new avenues to better understand different dietary behaviours, be they cultural or linked to eating disorders.

. © INRA, C. Leterrier

Emotional behaviour and the microbiota: studies launched on japanese quail

Every day, science is learning more and more about the relationship between behaviour and the microbiota. A study is currently underway on how the intestinal microbiota of Japanese quail influences the animals’ emotional behaviour and memory. Birds are the animal of choice in these studies as opposed to mice, because the microbial environment of bird embryos and the young can be better controlled without sacrificing natural birth by hatching or an early life that does not require the presence of the parents. INRA scientists implanted different microbiota into axenic fledglings in order to analyse the influence on their memory capacity and any behaviour changes. They focussed on fear, social motivation (regroupings between peers and social isolation) and reactions to new environments. The tests are run throughout the quails’ lifetime to determine the long-term effects of changes in intestinal microbiota. The first results will be published in 2017 and may well make important contributions to human health.