Food Emulsifiers Increase Pathogenicity of Certain Bacteria and Risk of Intestinal Inflammation

Certain bacteria of the intestinal microbiota (shown in red) are able to penetrate the normally sterile mucus layer (shown in green). © Benoit Chassaing

Diet is believed to play a role in triggering intestinal inflammation that can lead to the development of certain conditions, such as Crohn’s disease. Researchers from Inserm, CNRS and Université de Paris have shown that the emulsifiers present in many processed foods could have a harmful impact on specific bacteria in the gut microbiota, leading to chronic inflammation. Their findings have been published in Cell Reports.

The prevalence of chronic inflammatory bowel disease is increasing in all countries of the world and is thought to affect nearly 20 million people. Characterized by inflammation of the wall of part of the digestive tract, these conditions include Crohn’s disease and ulcerative colitis.

Several factors, both genetic and environmental, have been implicated in explaining the intestinal inflammation associated with these diseases. For several years, Inserm researcher Benoît Chassaing and his team at Institut Cochin (Inserm/CNRS/Université de Paris) have studied the role of diet, particularly the impact of certain additives such as emulsifiers.

Widely used by the food industry in many processed products, the purpose of emulsifiers[1] is to improve texture and extend shelf life. For example, lecithin and polysorbates ensure the smooth texture of mass-produced ice cream and prevent it from melting too quickly once served.

In previous studies based on animal models, the researchers had already shown that the consumption of dietary emulsifiers negatively alters the microbiota in such a way as to promote inflammation.

Moreover, in mouse models where the microbiota had been comprised of a low diversity of bacteria, they observed that the animals were protected against the negative effects of certain emulsifiers.

This led to their hypothesis that the emulsifiers would impact only specific bacteria, which are harmless under “normal” conditions but have the potential to cause disease. It is only in the presence of emulsifiers that these bacteria would be able to promote the development of chronic intestinal inflammation and its associated diseases.

E. coli as a model

As part of their study published in Cell Reports, the researchers used two mouse models: one without a microbiota and the other with a simple microbiota containing only eight species of bacteria. They colonized them with a strain of Escherichia coli (“AIEC bacteria”) associated with Crohn’s disease.

The researchers were interested in the effects of two emulsifiers administered following the colonization of the mice by the AIEC bacteria. Although the consumption of the emulsifiers had no harmful effects on the animals in the absence of these bacteria, they observed the development of chronic intestinal inflammation and metabolic deregulation when they were present. The presence of both the AIEC bacteria and the emulsifier was necessary and sufficient to induce chronic intestinal inflammation.

Further analysis revealed that when these bacteria were in contact with the emulsifiers, they over-expressed groups of genes that increased their virulence and propensity to induce inflammation. “We were able to identify a mechanism by which dietary emulsifiers can promote chronic intestinal inflammation in people who harbor certain bacteria, such as AIEC bacteria, in their digestive tract,” says Benoît Chassaing , who coordinated the study.

The next step is to list all the bacteria that have the same effects in contact with these food additives.

In the longer term, studies to identify and stratify patients according to the composition of their microbiota and risk of inflammation could be set up with the aims of taking a preventive approach and implementing personalized nutritional recommendations. People with specific microbiotas, sensitive to emulsifiers, could benefit from such recommendations.

“And while it is illusory to think that we can banish emulsifiers from our diet, the models and methodologies we have developed here will also allow us to test the action of several types of emulsifiers on the microbiota in order to identify those without harmful effects, and thus encourage their use,” concludes Chassaing.


[1] An emulsifier is a compound that has an affinity for both water and oil and allows the different phases of a compound to remain mixed together.

An Immune “Signature” to Identify Diabetic Patients at Risk of Developing Severe Covid-19

Researchers have identified biomarkers in blood samples taken from diabetic patients. © Inserm/Latron, Patrice

Type 2 diabetes is a risk factor for the development of a severe form of Covid-19. Identifying the immune- and inflammatory markers associated with these severe forms of the disease in this patient population would enable earlier and more appropriate care. Researchers from Inserm, the Paris hospitals group AP-HP and Université de Paris have identified an immune signature in hospitalized diabetic patients that would make it possible to predict the risk of admission to intensive care. Their findings have been published in EMBO Molecular Medicine and supplement those of other studies published in recent months on the identification of biomarkers predictive of severe forms of Covid-19.

In the early months of the Covid-19 pandemic, type 2 diabetes was identified as a risk factor for developing a severe form of the disease and has been linked to higher mortality. Therefore, understanding why this is and identifying biomarkers to predict which diabetic patients will progress to a severe form of Covid-19 requiring intensive care constitutes a research priority in order to improve their care and increase their chances of survival.

Type 2 diabetes is characterized by chronic inflammation, related to the disruption of adipose tissue which produces lipids recognized as “danger signals” by certain cells of the immune system. The immune response is then deregulated, leading to local and then systemic inflammation.

As part of the team led by Inserm Research Director Nicolas Venteclef at Cordeliers Research Center (Inserm/Université de Paris/Sorbonne Université), researchers Fawaz Alzaid and Jean-Baptiste Julla prepared an observational study in a hospital setting. It was conducted at the University Center for the Study of Diabetes and its Complications led by Jean-François Gautier, a diabetologist researcher at Lariboisière Hospital AP-HP. The objective was to better understand the link between pre-existing inflammation in diabetes and the risk of developing a severe form of Covid-19. The scientists sought to characterize the immune and inflammatory “signatures” of diabetic patients hospitalized following infection with SARS-CoV-2 and who presented severe symptoms of the disease.

They looked at the immune response of 45 patients hospitalized with Covid-19, thirty of whom had type 2 diabetes. Among the study participants, 35% of the diabetic patients developed a severe form of the disease requiring a stay in intensive care, compared to 25% of the non-diabetic hospitalized patients.

The researchers analyzed blood samples from all of the patients. They found that those most severely affected had fewer lymphocytes (a type of white blood cell) than those who had not been in intensive care. The team observed particularly low levels of cytotoxic CD8+ lymphocytes, immune cells particularly involved in the antiviral response with important functions of recognizing and eliminating infected cells. This was observed in all of the intensive care patients, regardless of diabetic status.

However, the diabetic patients having required intensive care differed from non-diabetic patients in the same case because they also had fewer monocytes (another type of white blood cell) in their blood. Changes in the morphology of these monocytes were also observed, as these immune cells in patients with type 2 diabetes had a larger average size than those found in blood samples from non-diabetic patients.

Finally, the researchers noted an increased presence of inflammatory markers associated with the type 1 interferon pathway, powerful antiviral molecules.

“These findings have major clinical implications as they suggest that there is an immune- and inflammatory signature specific to diabetic patients at risk of developing severe Covid-19. If physicians notice a decrease in monocyte frequency and a change in their morphology, they have the possibility to identify patients who will require further follow-up and potentially a place in intensive care. This will make it possible to refine and improve care,” explains Inserm researcher Fawaz Alzaid.

This research also provides data to support ongoing clinical studies that suggest the importance of a disruption of the type 1 interferon pathway in the development of severe forms of the disease, and the potential therapeutic value of anti-interferon drugs, already highlighted in recent research involving Inserm, published in Science.

A New Therapeutic Target for Type 2 Diabetes Discovered Thanks to a Rare Disease

An image representing a 3D photo of a human adipocyte: in green the ALMS1 protein reservoir, in red a part of the cytoskeleton, and in blue the cell nucleus. © Vincent Marion

A new therapeutic target for type 2 diabetes has recently been identified by researchers from Inserm and Université de Strasbourg, in collaboration with several European hospitals. The target in question is ALMS1, a protein whose function is still poorly understood. It has come to light thanks to the study of a rare disease, Alström syndrome, which affects different organs and associates childhood obesity and type 2 diabetes. This research paves the way for the development of a new drug and has been published in Diabetes.

Obesity and type 2 diabetes are strongly intertwined. Around 80% of obese subjects develop the disease, although the reasons for this association have not yet been clearly established. In order to study the links between them, the team of Inserm researcher Vincent Marion at the Laboratory of Medical Genetics (Inserm/Université de Strasbourg) focused on Alström syndrome, an extremely rare monogenic[1] disease that affects multiple organs, and leads to both obesity and type 2 diabetes.

This disease is caused by mutations in the ALMS1 gene coding for a protein whose function is still poorly understood. “The fact that it is a monogenic disease provided a starting point for studying the complex mechanisms of type 2 diabetes,” emphasizes Marion. The team found that abnormalities in adipose tissue caused by loss of ALMS1 function led to type 2 diabetes in people with Alström syndrome. What is more, in animals, restoring the function of this protein restored blood glucose balance. The researchers have therefore identified a new therapeutic target for type 2 diabetes: the ALMS1 protein.

These findings are the result of several years of research based on different clinical and experimental approaches, carried out in vivo in subjects with Alström syndrome and in a mouse model for the disease, as well as on in vitro observations. The researchers have identified abnormalities in the structure and function of adipose tissue in people with Alström syndrome that are far more significant than those found in obese individuals with the same body mass but without the disease. In mice, these abnormalities were associated with the inability of adipocytes, which make up the adipose tissue, to absorb glucose. “By preventing adipocytes from absorbing glucose, the loss of ALMS1 function is directly responsible for type 2 diabetes, making it a very interesting therapeutic target,” explains Marion.

ALMS1 therapeutic target in diabetes

In the study published in Diabetes, the researchers wanted to evaluate the therapeutic relevance of this protein by restoring the expression of the ALMS1 gene in their mouse model. Doing so restored blood glucose balance in these animals by increasing their glucose absorption.

The researchers also worked in vitro with adipocytes from people with Alström syndrome in order to understand the underlying molecular mechanisms that explain why this protein helps restore blood glucose balance. They found that in these adipose tissue cells, the ALMS1 protein acts far downstream of an insulin-controlled molecular signal chain.

“Thanks to this research using a rare disease model, we have discovered a molecule that by itself is capable of increasing glucose absorption by the adipocytes and maintaining good blood glucose balance. This makes it a very good therapeutic target for type 2 diabetes in general, whether or not it is associated with obesity,” explains Marion.

By identifying and using a molecule capable of targeting this ALMS1 protein in subjects with type 2 diabetes, the hope is to improve diabetes control, regardless of the level of circulating insulin in these individuals. A peptide is already under development.

Preclinical animal testing is being finalized and clinical trials are expected to begin in 2021 in subjects with type 2 diabetes, whether or not they are obese. Ultimately, if this drug candidate proves to be safe and effective, it could be prescribed alone or in combination with other diabetes drugs that target other molecular mechanisms.

On the strength of these results, the researcher has founded the company ALMS Therapeutics, in order to capitalize on this discovery.

[1] Genetic disease resulting from the mutation of a single gene

Fibromyalgia, Knowledge Overview and Recommendations: An Inserm Collective Expert Review

© Inserm/Frédérique Koulikoff

Fibromyalgia, otherwise known as fibromyalgia syndrome, is a form of chronic widespread pain associated with other incapacitating symptoms such as fatigue, cognitive impairment, sleep disturbances and mood disorders. This condition is thought to affect between 1.4 and 2.2% of people in France, but the lack of a specific biological marker makes diagnosing them difficult. Caring for these patients is also complex and often requires a multidisciplinary approach tailored to each individual.

Inserm was tasked by France’s Health Directorate with conducting a Collective Expert Review in order to take stock of the scientific knowledge on fibromyalgia in adults, and also to explore the potential existence of a similar syndrome in children and adolescents. The objective was also to recommend measures and establish research priorities in order to better understand fibromyalgia and improve patient care.

This Inserm Collective Expert Review is based on a critical analysis of the international scientific literature carried out by a multidisciplinary group of fifteen experts from fields including neurology, pharmacology, pediatrics, sociology and health economics.

All in all, nearly 1,600 scientific documents published over the last ten years were analyzed. The resulting review contributes a number of elements that enable the complex reality of fibromyalgia to be better understood, but also promote the appropriate care and strengthen research. The purpose was not to give an opinion on how the health authorities should manage the condition.

A complex clinical reality

While fibromyalgia is primarily associated with fluctuating chronic widespread pain, a large majority of patients also suffer from persistent fatigue, attention and concentration difficulties, and physical deconditioning (a psychophysiological process that leads to physical inactivity and withdrawal). Up to 85% present symptoms of anxiety or depression and 95% complain of sleep disturbances. However, what the review shows is that fibromyalgia is highly diverse in its clinical expression, with major variations in its severity. It also notes the impact of fibromyalgia on all aspects of quality of life and the significant economic and social costs associated with it.

As far as diagnosis is concerned, it is based on constantly evolving clinical criteria, which make it difficult, especially since no biomarker has yet been identified. The findings of the brain imaging studies performed so far vary greatly and do not make it possible to aid diagnosis.

What is more, the review recommends not distinguishing at present a juvenile fibromyalgia syndrome in children and adolescents suffering from chronic widespread pain.

Finally, the scientific research conducted over the previous decade rarely took into account the diversity of symptoms, the differences in severity and the various treatments taken by patients, which limits its scope. It also makes little distinction from other forms of chronic widespread pain, with sex-based differences and patient outcomes having not been explored in great depth.

Faced with this diversity of findings from the scientific literature, and in order to deal with the complex clinical reality of fibromyalgia, several recommendations are presented.

Offer the most appropriate patient care and encourage physical activity

The review emphasizes the need to promote support that adapts and evolves according to the symptoms. In all cases, the patient’s adherence to the proposed care program is essential. Appropriate interdisciplinary management in order to better recognize and accompany the various symptoms presented by patients is recommended for those whose quality of life is severely impaired.

Getting patients moving again at an early stage through appropriate physical activity is one of the central aspects of care in order to, among other things, prevent or minimize physical deconditioning. This is why the review suggests that the recommendations made in the Inserm Collective Expert Review on the practice of physical activity in chronic diseases be extended to include fibromyalgia. Such a physical activity program should be supervised regularly by a health professional.

For patients who have difficulty managing their fibromyalgia or who present symptoms of anxiety or depression, their management can include psychotherapy in order to help them improve their psychological wellbeing and quality of life.

While medications may be occasionally effective against certain symptoms (pain, but also sleep disorders, anxiety and depression…), it is important to prevent their misuse, particularly by avoiding the prescription of opioids for widespread pain, especially in children and adolescents.

Promote quality research

Another major recommendation is to develop and pursue quality research into widespread chronic pain, including fibromyalgia. Several lines of research must therefore be prioritized.

To begin with, the aim is to improve knowledge of fibromyalgia by exploring chronic widespread pain in large existing or future French cohorts. The studies will also be able to assess the particularities of fibromyalgia subgroups, strengthening research into patient representations and experiences and evaluating the socioeconomic impact.

In addition, the review stresses the importance of intensifying investigations in young people suffering from chronic widespread pain and research into the origin and consequences of such pain developing in childhood and adolescence.

Finally, the identification of factors that favor interdisciplinary care, particularly by promoting research into the organization of care, is also considered a priority.

Inserm’s Collective Expertise Review on Fibromyalgia is a further step towards promoting research of excellence on the subject, serving the health of people affected by chronic pain.

The Placenta Could Retain a Memory of Tobacco Exposure Prior to Pregnancy

©fotografierende on Unsplash

It is well-known that giving up smoking before pregnancy considerably reduces the health risks for both mother and child. Research by a team from Inserm, CNRS and Université Grenoble Alpes at the Institute for Advanced Biosciences, published in BMC Medicine, took a closer look at the subject showing for the first time that tobacco consumption, even when stopped before pregnancy, can have an impact on the placenta. By studying the placental DNA of 568 women, the team has shown that smoking not just during but also before pregnancy leads to epigenetic modifications (DNA methylation) which could have consequences on its course.

Although it has been shown that tobacco consumption during pregnancy has many negative health impacts for both mother and child, the mechanisms involved are still poorly understood. Previous studies have linked tobacco consumption during pregnancy to alterations in DNA methylation – a form of epigenetic modification (see boxed text) involved in gene expression – in umbilical cord blood and the cells of the placenta. Indeed, while the placenta plays a crucial role in the development of the fetus, it is vulnerable to many chemical compounds.

However, what had not been studied up until now was the impact on placental DNA methylation of tobacco exposure prior to pregnancy.

A team from Inserm, CNRS and Université Grenoble Alpes at the Institute for Advanced Biosciences measured and compared the impact of tobacco consumption on placental DNA methylation in pregnant women in the three months preceding pregnancy and/or during pregnancy.

The researchers studied DNA from samples of placenta collected at the time of delivery from 568 women of the EDEN1 cohort, who were divided into three categories: non-smokers (who had not smoked in the three months prior to pregnancy or during it), former smokers (who had given up smoking in the three months prior to pregnancy) and smokers (who had smoked both throughout pregnancy and in the three months prior to it).

In the smokers, the scientists observed that 178 regions of the placental genome showed alterations in DNA methylation. In the former smokers, they identified that DNA methylation was still altered in 26 of these 178 regions. Only in the women having smoked during pregnancy was methylation altered in the remaining 152 regions.

The regions that were altered most often corresponded to so-called enhancer zones, which remotely control the activation or repression of genes. In addition, some of them were located on genes known to play an important role in fetal development.

While many regions appear to have a normal methylation profile in women after they have stopped smoking, the presence of some DNA methylation changes in the placenta of those having stopped before pregnancy suggests the existence of an epigenetic memory of tobacco exposure,” says Inserm researcher Johanna Lepeule, who led this work. She suggests that changes in placental DNA methylation at the level of the genes related to fetal development and enhancer regions may partly explain the effects of smoking observed on the fetus and the subsequent health of the child.

The next steps in this research are aimed at determining whether these alterations impact the mechanisms involved in fetal development and whether they may have consequences for the health of the child.


[1] The pregnant women were recruited between 2003 and 2006 in the university hospitals of Nancy and Poitiers.


Learn more about epigenetic modifications and DNA methylation

Epigenetic modifications are materialized by biochemical marks present on DNA. Reversible, they do not lead to changes in DNA sequence but do induce changes in gene expression.  They are induced by the wider environment: the cell receives signals informing it about its environment, and specializes itself accordingly, or adjusts its activity. The best characterized epigenetic markers are DNA methylations, involved in the control of gene expression.

Nobel Prize 2020

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COVID-19 Vaccines: 25,000 Volunteers Needed for Large-Scale Clinical Trials in France – Registration Now Open


International research is being mobilized in order to develop safe and effective vaccines for COVID-19. Around thirty vaccine candidates are at the clinical evaluation stage, with some undergoing Phase 3 trials to demonstrate their efficacy. At the request of the Ministry of Solidarity and Health and the Ministry of Higher Education and Research, France – drawing on the excellence of its clinical research in vaccination – has taken steps to help evaluate the most promising vaccine candidates with the deployment of the COVIREIVAC platform. Driven by Inserm, COVIREIVAC federates 24 Clinical Investigation Centers (CICs) located in university hospitals across France, in close collaboration with the College of Teachers in General Practice. The clinical operational aspects of the various university hospitals are coordinated by the Paris Hospital Group AP-HP. Today, COVIREIVAC opens the registration process for volunteers to participate in the first large-scale clinical trials in France.

To make these trials possible, COVIREIVAC is looking for 25,000 volunteers aged 18 or over and has launched the registration and information website Developed with the support of Public Health France and the Medicines Agency (ANSM), it aims to provide the most accurate information possible on vaccine development so that potential volunteers can make an informed decision.

Join the fight

Volunteers in COVID-19 vaccine trials have a role to play in fighting the pandemic, moving research forward and thus contributing in the medium term to their own protection and that of their fellow citizens – particularly the most vulnerable. Becoming a volunteer also means participating in a scientific challenge alongside the scientific and medical community.

If you are interested in volunteering, simply pre-register at and complete a preliminary health questionnaire. Volunteers will then be contacted according to the needs of the various trial protocols (age, pre-existing conditions, geographical location), following which they can either confirm or withdraw their agreement to participate in the specific trial for which they have been called. It is also possible that they may never be called.

French research, a key player in developing safe and effective vaccines

Two vaccine clinical trials are currently ongoing in France: a Phase 1 trial in healthy subjects for a vaccine developed by Institut Pasteur in collaboration with CEPI, Themis and MSD which has begun at Cochin Hospital (Paris Hospital Group AP-HP), and a trial in healthcare workers on the contribution of the BCG vaccine to boosting systemic immunity and protection against COVID-19, which is coordinated by AP-HP.

Two types of large-scale clinical trial are envisaged in France. The first is Phase 2 trials to closely study the ability of vaccines to produce an immune response (immunogenicity) in elderly people, whose immune system is generally weakened despite being most at risk of developing severe forms of the disease. The second is Phase 3 trials for the large-scale study of the efficacy and safety of promising vaccine candidates, depending on the intensity of the virus’ circulation in France in the months to come.

These clinical trials could start between October and the end of the year, depending on the evolution of the epidemic and the ongoing discussions with industry.

“Good clinical trials are crucial for the development of safe and effective vaccines. As researchers and doctors, we are all committed to rigorous evaluation that will provide the health authorities with the essential data to guarantee the quality of the vaccines developed. What wenow need is volunteers to mobilize alongside us,” emphasizes Odile Launay, Professor of Infectious and Tropical Diseases at Université de Paris, coordinator of Cochin-Pasteur CIC at Cochin Hospital (AP-HP), and coordinator of COVIREIVAC.

In addition to the follow-up and monitoring of the volunteers during the trials, a specific system for monitoring participants will be set up by the platform at the end of the trials, in conjunction with primary care doctors and ANSM. This monitoring will therefore make it possible to track the safety of the vaccines over the long term.

COVIREIVAC, a “one-stop shop” for France

The COVIREIVAC platform is working in close collaboration with the Scientific Committee for COVID-19 Vaccines, chaired by Inserm Research Director and CARE Committee member Marie-Paule Kieny. The clinical trials conducted will focus on the most promising vaccines, selected by the Scientific Committee.