Seasonal influenza: launch of the 5th season of

Spread of influenza remains low in metropolitan France according to the weekly bulletin of 25/11/15 from the Sentinelles network, an information system based on a network of 1,300 general practitioners, with the incidence of influenza-illness estimated at 24 cases per 100,000 inhabitants, i.e. below the epidemic threshold (149 cases per 100,000 inhabitants).

Surveillance of the virus in metropolitan France continues nonetheless, with the launch of the fifth season of this Wednesday, 25 November. Originally launched in January 2012 by the Sentinelles network team (Inserm – UPMC) and the French Institute for Public Health Surveillance (InVS), offers everyone living in metropolitan France, whatever his/her health status, a chance to participate in influenza surveillance anonymously and voluntarily via its website.

The data thus collected help to complement traditional surveillance systems, provide real-time information on the spread of influenza among the metropolitan population, and contribute to research aimed at achieving a better understanding of the epidemic. Over 6,000 citizens have become involved in since the project was launched, thus becoming actively involved in influenza research and surveillance in France and Europe.


Current policies have failed to reduce the number of neural tube defects in Europe

Every year, nearly 5,000 pregnancies in Europe are affected by neural tube defects such as spina bifida and anencephaly (malformations of the brain and skull), with serious consequences for the newborn infants. Taking nutritional supplements containing folic acid (or vitamin B9) before and during early pregnancy may considerably reduce the risk, but studies show that only a minority of women do so. A study published today in The British Medical Journal, and coordinated by Babak Khoshnood, Inserm Research Director (Inserm Unit 1153 “Sorbonne Paris Cité Research Center in Epidemiology and Biostatistics”) concludes that there has been no decrease in neural tube defects over a 20-year period. The researchers urge the decision-makers to consider establishing a policy of mandatory folic acid fortification of some staple foods, such as flour or cereals.

new born baby

(c) Fotolia

The prevalence of neural tube defects in Europe has not decreased in the last 20 years, despite recommendations to women intending to have a child to supplement their folic acid intake, according to a study published in The BMJ today. 

The team led by Babak Khoshnood, Inserm Research Director, set itself the goal of evaluating the long-term trends in the number of cases of defective neural tube closure in Europe.

They analysed data on over 11,000 cases of defects from 28 EUROCAT (European Surveillance of Congenital Anomalies) registries, which cover approximately 12.5 million births in 19 countries between 1991 and 2011. Mathematical models were used in order to compare the differences between the registries. They found that the total prevalence of neural tube defects in 2011 was generally comparable to that observed in 1991 (9 per 10,000 births). This was also true for the two main types of defect, anencephaly and spina bifida. Estimates from the models show a 4% annual increase from 1995 to 1999, and a 3% decrease between 1999 and 2003, followed by a stabilisation in the subsequent years.

Trends for spina bifida and anencephaly were comparable, and no substantial decrease was observed for these two defects.

The authors emphasise that this is an observational study, and that no definite explanation as to cause and effect can therefore be drawn from these results. However, they claim that their data make it possible to conclude that “Recommendations, voluntary fortification, or both have not been effective in decreasing the prevalence of neural tube defects.”

There is no plan in Europe to make it mandatory to add folic acid to some staple foods such as flour or cereals, which happens in many countries such as the United States and Canada. Moreover, studies suggest that this approach increases folic acid intake enough to halve the prevalence of neural tube defects, while no serious side effects have been observed to date.

According to the researchers, the conclusions of this new study “should encourage the relevant European authorities to take a closer look at mandatory fortification.”

Gut Microbes Signal to the Brain When They’re Full

Press release written by Cell Press

Don’t have room for dessert? The bacteria in your gut may be telling you something. Twenty minutes after a meal, gut microbes produce proteins that can suppress food intake in animals, reports a study published November 24 in Cell Metabolism. The researchers from Inserm and Rouen University also show how these proteins injected into mice and rats act on the brain reducing appetite, suggesting that gut bacteria may help control when and how much we eat.

The new evidence coexists with current models of appetite control, which involve hormones from the gut signalling to brain circuits when we’re hungry or done eating. The bacterial proteins—produced by mutualistic E. coli after they’ve been satiated—were found for the first time to influence the release of gut-brain signals (e.g., GLP-1 and PYY) as well as activate appetite-regulated neurons in the brain.

“There are so many studies now that look at microbiota composition in different pathological conditions but they do not explore the mechanisms behind these associations,” says senior study author Sergueï Fetissov of Rouen University and Inserm’s Nutrition, Gut & Brain Laboratory in France.

“Our study shows that bacterial proteins from E.coli can be involved in the same molecular pathways that are used by the body to signal satiety, and now we need to know how an altered gut microbiome can affect this physiology.”

Mealtime brings an influx of nutrients to the bacteria in your gut. In response, they divide and replace any members lost in the development of stool. The study raises an interesting theory: since gut microbes depend on us for a place to live, it is to their advantage for populations to remain stable. It would make sense, then, if they had a way to communicate to the host when they’re not full, promoting host to ingest nutrients again.

In the laboratory, Fetissov and colleagues found that after 20 minutes of consuming nutrients and expanding numbers, E. coli bacteria from the gut produce different kinds of proteins than they did before their feeding. The 20 minute mark seemed to coincide with the amount of time it takes for a person to begin feeling full or tired after a meal. Excited over this discovery, the researcher began to profile the bacterial proteins pre- and post-feeding.

They saw that injection of small doses of the bacterial proteins produced after feeding reduced food intake in both hungry and free-fed rats and mice. Further analysis revealed that “full” bacterial proteins stimulated the release of peptide YY, a hormone associated with satiety, while “hungry” bacterial hormones did not. The opposite was true for glucagon-like peptide-1 (GLP-1), a hormone known to simulate insulin release.

The investigators next developed an assay that could detect the presence of one of the “full” bacterial proteins, called ClpB in animal blood. Although blood levels of the protein in mice and rats detected 20 minutes after meal consumption did not change, it correlated with ClpB DNA production in the gut, suggesting that it may link gut bacterial composition with the host control of appetite. The researchers also found that ClpB increased firing of neurons that reduce appetite. The role of other E.coli proteins in hunger and satiation, as well as how proteins from other species of bacteria may contribute, is still unknown.

“We now think bacteria physiologically participate in appetite regulation immediately after nutrient provision by multiplying and stimulating the release of satiety hormones from the gut,” Fetisov says. “In addition, we believe gut microbiota produce proteins that can be present in the blood longer term and modulate pathways in the brain.”

Defective connections throughout the brain involved in certain autistic disorders

Researchers at Neurocentre Magendie (Inserm/University of Bordeaux) have just shown how altered connections between cells of the nervous system are involved in fragile X syndrome, a cause of severe autistic spectrum disorders. Using MRI, Andreas Frick, Inserm Research Fellow, and his team have actually observed, in a mouse model of this syndrome, an alteration in the connections and communication between different areas of the brain. These new data are likely to explain certain symptoms of autistic spectrum disorders, such as hypersensitivity to sensory information and alterations in visual perception.
Details of this work are published in the 20 November 2015 issue of Science Advances.


Recent estimates from the US Center for Disease Control suggest that one child in 68 suffers from Autistic Spectrum Disorders (ASD). ASD are neurological disorders characterised by a spectrum of symptoms, including problems with social interaction and communication, abnormal processing of sensory information, and stereotypic repetitive behaviours.
It has long been suggested that the brain of individuals with autism shows different connections. However, there is still no consensus either in regard to a model for these differences, or a possible link between these differences and the symptoms expressed by people suffering from these disorders.
A theory is currently emerging among neuroscientists at international level that suggests that the brain of individuals with ASD is “hyper-connected” at local level, but that overall, the different areas of the cortex are functionally “disconnected” from one another. The local connections can “process” a specific type of information (some aspects of vision, for instance). Conversely, longer range connections allow the brain to integrate more complex information from parts of the brain that often deal with different aspects. This latter type of connection is therefore needed for fine perception and understanding of our external environment.

PhotoCP Frick

Reorganisation of local and long-range connections in a mouse model of autism (right) and a wild-type mouse (left)
Neurons that become fluorescently labelled (in green) following injection of a tracker dye into the primary visual cortex (white arrow) send projections to the visual cortex and are distributed throughout different regions of the brain. In the fragile X mouse model (Fmr1-/y), one can observe a high density of neurons in the visual cortex (local connections), but a reduced number of neurons at a distance from this region (long-range connections).

Figure taken from Haberl et al. Science Advances 20 November 2015; 10.1126/sciadv.1500775. This figure is licensed under CC BY-NC. Modification of Figure 2a from the publication (modified thresholding and viewing angle, and removal of red mark indicating the point of injection).

To study how the brain network is changed in ASD, Andreas Frick and his colleagues used a mouse model of fragile X syndrome (FXS, a neurodevelopmental disorder closely linked to autism). In 2014, this same team had observed, in these mice mimicking ASD and FXS, alterations in the manner of reacting with sensory information (especially information associated with touch), and described a mechanism explaining the neurobiological changes underlying this phenomenon .
In the present work, the researchers from Andreas Frick’s team (in collaboration with a Dutch team) used magnetic resonance imaging (MRI), a technique frequently used in humans, to better demonstrate the disruption of connections between the neurons. Indeed, their results show disorganisation of the nerve fibres of the corpus callosum of these mice. The corpus callosum contains nerve fibres that connect the neocortical areas to one another and to other regions of the brain.
“Together, the brain connections work like a motorway, enabling traffic to be distributed to different parts of a town, as well as to other towns and villages on the outside,” explains Andreas Frick. The researchers wanted to take a closer look at the role of neocortex, which processes visual information.
Overall, functional MRI indicated reduced communication between different areas of the brain.
All these results support the idea that local connections are increased in FXS/ASD, but that long-range connections are reduced. As a result, this work confirms the long-held assumptions (mentioned above), and also provides an explanation for some of the symptoms of ASD and FXS. For example, over-processing of local information and/or an inability to integrate information coming from multiple sources may explain altered sensory perception. Alterations in visual perception, characteristic of ASD, may be explained by over-processing of fine detail or structures at the expense of the overall picture.
“MRI techniques presented in our work are also routinely used in humans, and therefore constitute a method applicable to patients for measuring changes in connections,” explain the researchers. “Transposed to humans, our results could make it possible to change the manner of evaluating new therapeutic approaches for treating FXS and ASD, and to better understand the potential role of modified connections in other psychiatric or neurodevelopmental disorders,” they conclude.

Pier-Vincenzo Piazza receives the Inserm Grand Prix 2015

On 8 December next, at Collège de France, the Inserm Prizes for 2015 will be awarded to eight outstanding researchers and research engineers. The Inserm Grand Prix 2015 will be awarded to Pier-Vincenzo Piazza, in recognition for his body of work on the physiopathology of psychiatric illnesses, in the presence of Marisol Touraine, Minister of Social Affairs and Health, Thierry Mandon, Secretary of State for Higher Education and Research, Professor Yves Lévy, Chairman and Chief Executive Officer of Inserm, and Jean-Yves Le Déaut, Member of Parliament and President of the Parliamentary Office for Scientific and Technological Assessment (Opecst).

Caroussel PV Piazza


© Inserm / Patrick Delapierre

Pier-Vincenzo Piazza, Inserm Grand Prix

The Inserm Grand Prix is awarded to Pier-Vincenzo Piazza, Inserm Research Director and Director of Inserm Unit 862, “Neurocentre Magendie,” for his body of research on the physiopathology of psychiatric illnesses. Both a physician and psychiatrist, Pier-Vincenzo Piazza has devoted himself to experimental psychiatric research in order to develop new treatments for mental disorders.

He was the first to demonstrate the existence of individual vulnerability to addiction, thus proposing the basis for the physiopathology of addiction.

He recently identified a mechanism that can naturally protect the brain from the harmful effects of cannabis in animals, something that has enabled him and his team to reveal a new class of pharmacological agents and to select the first candidate drug, AEF0117. This drug, which will be tested in clinical trials in 2016, is able to inhibit the behavioural effects of THC. This discovery paves the way for potential treatments for cannabis addiction.


Peter Piot, International Prize

The International Prize is awarded to Peter Piot, a physician specialising in microbiology and former Director of Onusida, in recognition for his body of research on deadly viruses. He jointly discovered Ebola virus in 1976, and has actively worked to combat HIV. As Director of the London School of Hygiene and Tropical Medicine, he is currently involved in researching a vaccine for Ebola virus.


Étienne-Émile Baulieu, Honorary Prize

The Honorary Prize distinguishes Professor Étienne-Émile Baulieu, researcher at Inserm Unit “Steroids, Neuroprotection and Neuroregeneration” (Inserm Unit 1195), for his work on steroid hormones. Recognised throughout the world for having discovered DHEA secretion by the adrenal glands and for having invented the abortion pill, he is currently working on an approach to Alzheimer’s disease.


The Opecst-Inserm Prize is awarded to José-Alain Sahel, ophthalmologist, founder and Director of The Vision Institute (Inserm Unit 968), a pioneer of artificial retina research and regenerative eye treatments.

The Research Prizes are awarded to Caroline Robert, physician and Codirector of the Melanoma Research Team at Inserm Unit 981, for her work on melanoma, and to Archana Singh-Manoux, Inserm Research Director at the “Center for Research in Epidemiology and Population Health” (Inserm Unit 1018), in recognition for her studies on cognitive ageing.

This year, Innovation Prizes honour René Ferrera, an Inserm research engineer at the CarMeN Laboratory (Inserm Unit 1060), whose achievements include the development of new techniques for the protection and evaluation of myocardial viability, and Claire Lissalde, a research engineer and head of Inserm’s audiovisual service (Department of Scientific Information and Communication), for her original work in science outreach.

A new neural circuit involved in the control of movement

The team led by Claire Wyart, an Inserm researcher at the Brain and Spine Institute, has just demonstrated the ability of sensory neurons located in the spinal cord to modulate movement. In the zebrafish, the researchers have shown that activation of these neurons triggers locomotion when the animal is at rest, and inhibits it when the animal is moving. These results offer hope that it will one day be possible to specifically stimulate these circuits in order to generate movement in patients with spinal cord injuries. This work is published in Current Biology.


Spinal cord injuries lead to serious paralysis for which, to date, there is no treatment. When communication between the brain and spinal cord is interrupted, the brain can no longer control movements voluntarily. However, the spinal cord contains autonomous circuits that generate movement, and ensure that locomotion proceeds once the decision to move has been taken at brain level. This capacity for sustaining movement comes from the ability of the spinal locomotor network to generate electrical oscillations.

In order to understand the functioning and modulation of the spinal locomotor network, Claire Wyart’s team studies motor activity in the zebrafish. This transparent vertebrate species is particularly suited to optogenetics, an innovative technology that allows stimulation of target neurons using light. In this method, the stimulated neurons light up and are visible in the transparent animal.

The researchers exploited this technology to identify and understand the functioning of a new neural circuit involved in the control of movement. By activating the circuit at different times (animal at rest or moving), the researchers demonstrated connections that can generate the oscillations that allow the fish to move. The originality of this circuit is that it depends on the activity of sensory neurons, which, through a cascade effect, ultimately activate motor neurons.

Surprisingly, the researchers find that modulation of movement depends on the animal’s initial state. In fact, stimulation triggers movement when the animal is in a resting state, whereas it inhibits it when the animal is already swimming. “This modulation is complex, and will depend on the context,” explains Claire Wyart, the main author of this work.

In 2014, this same team had shown that this circuit is conserved among the different vertebrate species, particularly in primates. This original work in the zebrafish thus opens many avenues of research for understanding the modulation of the locomotor circuit in humans.

For the first time, a class of sensory neurons that can modulate the spinal locomotor network has been identified.

Although several points remain to be clarified, stimulation of the sensory pathways to activate the locomotor network that generates walking in humans represents hope in cases of spinal cord injury.

Inserm goes into space with Thomas Pesquet

In one year’s time, French ESA astronaut Thomas Pesquet will take off for the International Space Station (ISS), on board which he will conduct scientific experiments prepared by researchers from Inserm. The scientific and technical programme for this ESA (European Space Agency) mission includes significant participation by France, managed by CNES (National Centre for Space Studies). Research projects from 3 Inserm laboratories will be conducted in orbit. Their purpose will be to study the effects of space on bone density, blood pressure and sleep. Data collected before, during and after the 6-month mission will be analysed by the researchers back on earth to obtain a better understanding of the related pathologies.

 PhotoCP web Thomas Pesquet

© Inserm/Delapierre Patrick

To find out more about the experiments to be conducted by Thomas Pesquet, read the complete file prepared by Inserm’s magazine:

Espace – L’Inserm en orbite (Space – Inserm in orbit) (Science&Santé No. 27, only in French)

Listen to the interview with Thomas Pesquet conducted on behalf of Inserm at the Paris Airshow (a coproduction of Inserm/CNES):

For your information, Inserm, a scientific partner of the flight operated by ESA, is holding a citizens’ conference, which will be attended by the researchers involved and Claudie Haigneré:

Conquête spatiale et innovation médicale (Conquest of space and medical innovation): 26 November, 7:00-8:30 pm Cité des sciences et de l’industrie de Paris, Museum de Toulouse (simultaneous production, as part of Futurapolis)

Follow on @InsermLive

3 Inserm laboratories involved in 4 experiments:

  • Inserm Unit 1075, “Mobilities: Attention, Orientation and Chronobiology” (Caen)

The research team will study space sickness and its relationship with travel sickness. Technologically, the laboratory is working with the Bodycap company on miniaturised actigraph and temperature sensors, and the corresponding analytical software. These sensors will be loaded into a smart vest which will be worn by Thomas Pesquet.

Pierre Denise

Inserm Unit 1075, “Mobilities: Attention, Orientation and Chronobiology” (Caen)

+33 (0)2 31 06 81 32



  • Inserm Unit 1059, “Integrative Biology of Bone Tissue” (St Etienne)

– This laboratory will study changes to bone due to space flight, and recovery on returning to earth.

– A second experiment, conducted in vitro, will be aimed at understanding why in space, bone marrow precursor cells differentiate into adipocytes at the expense of osteocytes, the main cause of reduced bone formation and hence of bone loss.

Laurence Vico

Inserm Unit 1059, “Integrative Biology of Bone Tissue”

+33 (0)4 77 42 18 57



  • Inserm Unit 970, “PARCC (Paris Cardiovascular Research Center)” – “Physiopathology, pharmacology and imaging of arteries” team (Paris)

Space flights are good models for the study of accelerated ageing, in that some preliminary data indicate that arterial stiffness may increase by an equivalent of approximately 10 years during short space flights. Changes related to microgravity will be studied with the help of specially developed flexible sensors (in collaboration with ESIEE Paris and the ESYCOM laboratory

Pierre Boutouyrie
Inserm Unit 970 PARCC
+33 (0)1 56 09 39 66

An indicator for predicting emergence from coma

It is difficult to judge the progress of patients in a coma following head trauma or recovery from cardiac arrest. Researchers from Unit 825, “Brain imaging and neurological handicaps” (Inserm/Université Toulouse III – Paul-Sabatier), in collaboration with Toulouse University Hospital, show that the quality of communication between two structures in the brain predicts patient recovery at 3 months. This new indicator, obtained by conducting MRI analysis on the brain of patients at rest, may provide additional help in establishing a prognosis.

Results of this study are published in the 11 November issue of the journal Neurology.

See video on the discovery presented by Patrice Péran, Inserm Research Fellow

Consciousness appears to be a complex mental process, inseparable from our existence. In reality, this capacity is relatively unstable. It disappears in a cyclical manner during the day (wake-sleep), and can be modified by administering certain drugs (anaesthesia). Finally, it can be abolished more or less completely and permanently following an insult to the brain; this happens in a coma. It is very difficult to determine which patients will emerge from such a situation and regain a normal state of consciousness, and conversely, which will be left with major neurological sequelae leading to serious disability (vegetative state, state of minimal consciousness).

In this study, the researchers focused on the brain abnormalities responsible for the loss of consciousness observed during coma. They compared the activity of the brain at rest in 27 patients in this state, and of control subjects of the same age, using functional magnetic resonance imaging recordings.

Two regions of the brain no longer communicate with each other.

The scientists particularly analysed communications between the brain as a whole and one structure located at the back of the brain known as the posteromedial cortex (PMC). Activity in this key region is reduced during sleep or anaesthesia. This structure is made up of two areas that the researchers studied (the precuneus and the posterior cingulate cortex)

A major loss of communication between the PMC and the anterior part of the brain (medial frontal cortex, MFC), particularly at the level of the posterior cingulate cortex, is seen in all comatose patients. This bad connection is present regardless of the mechanism responsible (head trauma or cardiac arrest with subsequent recovery). This observation suggests a major role for the interaction between these two structures in the emergence of consciousness in humans.

Schéma mauvaire connexion en

3D representation of the brain and areas involved (posterior cingulate cortex in blue, medial frontal cortex in yellow) © Inserm Unit 825

The team went further, and evaluated the extent to which this connection becomes altered with time. The researchers at Inserm compared recordings a few days after the brain insult and onset of coma with the neurological profiles of the patients three months later. It turns out that patient recovery is closely associated with the degree of involvement of this connection.

“Patients who are going to recover consciousness show levels of connections comparable to those found in healthy subjects. Conversely, a reduction in communication between the two areas predicts an unfavourable progression towards a vegetative state, or minimally conscious state,”

explain Stein Silva and Patrice Péran, who made this discovery.

These results constitute an important step in understanding the emergence of conscious perception of the outside world. They are promising, since neurologists might use this parameter to form a prognosis and develop treatment plans for comatose patients. However, research must be continued in order to decipher the mechanisms underlying coma, which are still poorly known.

November 14th 2015: world diabetes day

Initiated by the International Diabetes Federation and the World Health Organization, World Diabetes Day, which takes place next Saturday, 14 November, is aimed at sensitising and informing the general public about diabetes prevention and management.


Diabetes, type 1 or type 2, is a chronic disease characterised by insufficient production of insulin, or by poor use of this hormone by the body. This is manifested in a high concentration of sugar in the bloodstream (hyperglycaemia), which in time can damage the nerves, blood vessels, heart, eyes and kidneys.

In 2014, 9% of the population was diabetic.[1] WHO predicts that by 2030, diabetes will be the seventh leading cause of deaths worldwide.[2]


Inserm researchers are involved in combating this disease on a year-round basis. Here is our latest news on the theme:

Research by Maud Le Gall at Inserm Unit 1149, “Center for Research on Inflammation,” and by her collaborators focuses on the effects of surgery on intestinal metabolism. Their recent work has shown that the reconfigured intestine following bariatric surgery might be the cause of improved control of glycaemia and type 2 diabetes.

See the press release, “Obesity: surgery corrects diabetes even before weight loss occurs,” in the press room section.


Work by Julien Diana, Inserm Unit 1151, “Necker Institute for Sick Children,” has demonstrated protection conferred by the microbiota in the development of type 1 diabetes in mice.

Injection of cathelicidins inhibits the establishment of inflammation in the pancreas, and thereby suppresses the development of autoimmune diabetes in mice,” says Julien Diana.

Preliminary data, as well as the scientific literature, suggest that a similar mechanism might exist in humans, leading the way for new therapies for autoimmune diabetes.

See the press release, “Bacteria that Prevents Type 1 Diabetes,” in the press room section.


Researchers at Inserm Unit 897, “Inserm Epidemiology and Biostatistics Research Center” (Inserm/University of Bordeaux) and CIC-1401 Clinical Investigation Centre, in collaboration with Bordeaux University Hospital, have shown for the first time the impact of diabetes and pre-diabetic status on neurocognitive performance in people living with HIV, regardless of age.

See the press release, “Diabetes is associated with neurocognitive disorders in people living with HIV,” in the press room section.

[1] Global status report on noncommunicable diseases 2014. Geneva, World Health Organization, 2012.

[2] World Health Organization. Global Health Estimates: Deaths by Cause, Age, Sex and Country, 2000-2012. Geneva, WHO, 2014.

Fatty acids, essential for the nervous system… of the gut (as well)

How does a fatty acid deficiency explain Crohn’s disease?

Two Inserm research teams have just shown that failure of the intestine to produce a lipid “messenger” is associated with Crohn’s disease, a common and highly disabling inflammatory bowel disease (IBD). This messenger, derived from an essential fatty acid, regulates the permeability of the intestinal barrier, and could thus become a choice target in the management of IBD. These studies also throw fresh light on the role of the enteric glial cells. Like their counterparts in the central nervous system, for too long considered to play a “secondary role,” the intestinal glial cells are starting to “show their hand,” which is actually indispensable to intestinal homeostasis. Details of this work are published in Gastroenterology.

The enteric nervous system plays a central role in controlling the homeostasis of the digestive functions, such as motor function, and in controlling the functions of the intestinal epithelial barrier. This integrative nervous system, located along the entire length of the digestive tract, is made up of neurons and glial cells. Much remains to be discovered about the role of the enteric glial cells. A growing number of studies shows that they regulate, in a manner analogous to the astrocytes in the brain, the functions of the enteric neurons, as well as those of the intestinal epithelial barrier, such as the proliferation of epithelial cells, their migration and permeability (paracellular and transcellular), and repair processes. Glial cells regulate these functions by liberating different glial mediators, including certain lipid metabolites of n-6 polyunsaturated fatty acids (PUFA).

Otherwise, characterisation of enteric glial cell (EGC) involvement in diseases associated with dysfunctions of the intestinal barrier remains limited to description of the altered expression of glial markers. These dysfunctions in the intestinal barrier (increased permeability, failure in repair) are recognised as playing a possible key role in inflammatory bowel disease (IBD) by helping to trigger recurrences. Reducing these dysfunctions is also a likely mechanism of action of the biotherapies used in the management of IBD.

In this context, Malvyne Rolli Derkinderen and Michel Neunlist, researchers in the Inserm/Nantes University Joint Research Unit “Neuropathies of Enteric Nervous System and Digestive Diseases: Involvement of Enteric Glial Cells,” and their collaborators at the Toulouse Purpan Digestive Health Research Institute (IRSD) initially sought to characterise the production of lipid mediators derived from n-6 fatty acids in animal and human enteric glial cells. They then analysed the impact of the most abundantly produced PUFA metabolites on the functions of the intestinal epithelial barrier, and ultimately demonstrated that production of one of them was defective in patients with Crohn’s disease.

shema neunlist en

In green: under physiological conditions, the enteric glial cells produce lipid metabolites including 15-HETE, which strengthens the resistance of the intestinal epithelial barrier, and prevents entry of pathogens. In red: during Crohn’s disease, there is a deficiency in glial production of 15-HETE, which leads to an increase in the permeability of the barrier, and facilitates the entry of pathogens. This may contribute to disease recurrence or severity.

Thus the researchers showed that human (as well as rat) EGC are able to produce n-6 PUFA, especially 15-HETE, synthesised by 15-lipoxygenase-2. This 15-HETE strengthens the intestinal epithelial barrier, and reduces paracellular permeability in vivo and in vitro, particularly by increasing the expression of tight-junction molecules including zonula occludens-1. In EGC isolated from patients with Crohn’s disease, the researchers demonstrated defective production of 15-HETE, associated with a loss of ability of the EGC to control the permeability of the intestinal epithelial barrier.

This work therefore identifies n-6 PUFA as a source of metabolites with potentially beneficial effects on the functions of the intestinal epithelial barrier in IBD. For Camille Pochard and Sabrina Coquelorge, the two first authors,

“These results help to underscore the role of the glial cells in particular, and of the enteric nervous system in general, in the physiopathological processes involved in IBD, and to identify new targets of therapeutic interest.”