Pancreatic Cancer: a “Multiomic” Study Identified Two Tumor Subtypes, and a Potential New Treatment Avenue

© Crédit Fotolia

Juan Iovanna (Inserm Research Director) and his colleagues at the Marseille Cancer Research Center (Inserm/CNRS/Aix Marseille Université/Institut Paoli-Calmettes), in close collaboration with the “Tumor identity cards (CIT)” program run by the Ligue nationale contre le cancer and the University of Wisconsin (United States), have generated a “bank” of approximately 200 viable human pancreatic tumors, and cells derived from these tumors. The “multiomic” analysis of these tumors, i.e. the general characterization of all alterations in gene expression, epigenetic modifications of DNA methylation, has evidenced two main tumor subtypes. The specific characteristics of these subtypes, identified by the researchers, could open up new therapeutic approaches. The results of this research have been published in the journal Cell Reports.

With a 5-year survival rate of less than 5%, pancreatic cancer has the bleakest prognosis compared to all other types of cancer. Surgery is still currently the best possible treatment for the 15 to 20% of patients with a resectable tumor, with life expectancy of 15 to 18 months. When metastases develop, life expectancy is then estimated at between 3 and 6 months. Chemotherapy and radiotherapy only have limited efficacy.

Like other types of cancer, pancreatic cancer is caused by a combination of genetic, epigenetic (biochemical modifications affecting the genome) and environmental factors, which give rise to very heterogeneous disease profiles, with strongly contrasting profiles in terms of symptoms, susceptibility, and patient response to treatment. Owing to this heterogeneity, it is very important to be able to distinguish between the different types of patients, according to their profile in terms of susceptibility to available treatments.

Approved by the Ligue nationale contre le cancer, the Inserm team led by Juan Iovanna has generated a “bank” of approximately 200 viable human pancreatic tumors (PDAC), from xenografts in mice, and cells derived from these tumors. Analysis of the first 29 tumors shows that these models remarkably reproduce the tumor characteristics in patients, together with their interaction with the immediate tumor environment – known as the microenvironment or stroma. These model have the advantage of being able to differentiate between transformed human tumor cells and non-transformed murine stromal cells.

The genomic research program in cancer “Tumor Identity Cards (CIT)”, initiated and supported by the Ligue nationale contre le cancer, conducted a series of “omic” analyses, i.e. the characterization of all alterations in gene expression and epigenetic modifications of DNA methylation. The researchers have observed that these alterations give rise to changes in gene expression and have an impact on the presence of immune cells in the tumor microenvironment, both in transformed cells and in the host animal stroma.

This extensive multiomic profiling evidenced two main subtypes of PDAC each of which have specific clinical consequences. These subtypes present specific alterations of methylation and gene expression, together with signaling pathways involved in the “dialog” between cancer cells and stromal cells. The analysis of these pathways points to new therapeutic avenues. These results reveal the complex and diverse interaction between PDAC tumors and the stroma.

In conclusion, the data presented in this research show that xenografts constitute a suitable model for pre-clinical studies and reproduce the diversity of primary cancer involving reconstitution of the stroma. The multiomic analysis is a valuable source of new reliable therapeutic targets with a view to treating patients suffering from PDAC.

An Edible Mushroom With Potential to Fight Human Genetic Diseases

Credits @ MNHN/CNRS – Christine Bailly

Could a common mushroom help fight certain genetic diseases? Although surprising, this is indeed the new discovery made by French scientists from Inserm, the French National Museum of Natural History, the CNRS, Université de Lille, and the Institut Pasteur de Lille[1]. By examining numerous extracts, the scientists thus evidenced that the mushroom, Lepista inversa, acted significantly on three isolated cell lines taken from patients with cystic fibrosis. This research was published in .Plos One

[1] Mechanisms of Tumorigenesis and Target Therapies Laboratory (CNRS, Université de Lille, Institut Pasteur de Lille), and Microorganism Communication and Adaptation Molecule Laboratory (MNHN, CNRS)

Approximately 10% of patients with rare genetic diseases such as cystic fibrosis or Duchenne muscular dystrophy (or more common genetic diseases, such as certain types of cancer) have a nonsense mutation, i.e. of a change in DNA sequence. This mutation is evidenced by the presence of a “stop codon” which does not code for a known amino acid and prematurely stops the synthesis of proteins from mutated genes. As a result, the proteins obtained are truncated and do not function properly. Unable to fulfill their role in the body, they have familiar harmful consequences: bronchial obstruction and inability to breathe in cystic fibrosis, and muscular degeneration in muscular dystrophy.

Several strategies are now being developed to correct the consequences of a nonsense mutation. One of the most promising avenues is translational readthrough. This involves the cellular machinery continuing protein synthesis despite the presence of a “stop codon” in the DNA. For this purpose, when the RNA is transformed into protein, “decoy” molecules located in the environment very close to the cellular machinery may catch it unawares and enable a complete protein to be produced, as if there was nothing amiss. Nevertheless, the molecules capable of playing this role and identified to date display very limited efficacy and/or considerable toxicity.

@ Taken from Médecine sciences


ATG            STOP                       DNA


AUG                                            mRNA


mRNA degradation by the NMD pathway

Termination                              Readthrough inducers

Truncated protein                       Full-length protein


Figure 1. Therapeutic strategy in stop codon diseases. A nonsense mutation in a gene (DNA) causes the appearance of a premature stop codon on the mRNA which is translated by the ribosome. This triggers the synthesis of a truncated protein and possibly the degradation of this mRNA by the NMD pathway (nonsense mediated mRNA decay), which specifically recognises mRNAs containing a premature stop codon. Certain compounds, by inducing passage through the premature stop codon (an event known as “readthrough”), enable the synthesis of a full-length protein, which could bring therapeutic benefit to patients with a nonsense mutation.

By combining their expertise and using a screening system on the chemical-extract libraries at the French National Museum of Natural History, two teams of scientists[1] succeeded in demonstrating that the extract of a mushroom, Lepista inversa or Clitocybe inversa, is capable of very effectively restoring the expression of human genes presenting nonsense mutations on cells in culture.

Thanks to the partnership between the two research laboratories, the CHU de Lille, Hospices Civils de Lyon, Cochin Hospital, and the charity Vaincre la Mucoviscidose, researchers were also able to evidence significant activity on cells from patients with cystic fibrosis[2].

“Given that only 5% of functional proteins need to be restored in cystic fibrosis to have an impact on the consequences of the disease, this research is extremely encouraging,” according to the authors who point out that this strategy also has the advantage of not affecting the patients’ genetic inheritance.

“This discovery brings hope as this mushroom is edible, although it is not particularly prized for its taste; it is also very common – it grows in the Ile-de-France region, and in various regions of France and Europe,” explains Fabrice Lejeune, Inserm researcher and the last author of this research. “There is still a long way to go before we can develop a genuine therapeutic strategy,” he adds. “We still need to find a way to purify the molecules of interest present in this extract, and then carry out in vivo tests to verify their long-term efficacy and the absence of toxicity.”

This multidisciplinary study also demonstrates the value of the extract collection kept in the extract bank at the museum for teams of biologists and chemists working in the health field.

[1] Mechanisms of Tumorigenesis and Target Therapies Laboratory (CNRS, Université de Lille, Institut Pasteur de Lille), and Microorganism Communication and Adaptation Molecule Laboratory (MNHN, CNRS)


Ribosome Plasticity: a New Avenue in Targeted Cancer Therapy


The “Nuclear Domains and Pathologies” team led by Jean-Jacques Diaz, Inserm Research Director at the Cancer Research Center of Lyon (Inserm/CNRS/Université Claude Bernard Lyon 1/Centre Léon Bérard), has recently demonstrated that one of the essential components of the “cellular machinery” that produces proteins – the ribosome – is altered in tumors. The researchers have observed that these modified ribosomes function differently in cancer cells, preferentially producing proteins that favor cancer cell proliferation and survival.  This discovery opens up new possibilities for the development of innovative cancer therapies that target this abnormal machinery. This research has been published in Proceedings of the National Academy of Sciences (PNAS).

The research performed by Jean-Jacques Diaz and his team focuses on a key cell function: the production of proteins via “small specialist robots” called ribosomes. Their task is to retrieve coded genetic messages and decode them in the form of active proteins. These proteins then go on to play roles in various physiological mechanisms of the body, such as the insulin involved in blood glucose control.

The abnormally high metabolic activity and proliferation of cancer cells require the production of additional protein. In a major study published in Cancer Cell[1] in 2013, the researchers identified certain ribosomal modifications that occur during the development of breast and colon cancers, and which promote the development of these diseases. In the study published this month in PNAS, coordinated by CNRS Research Officer Frédéric Catez, the team in Lyon demonstrated the mechanism by which these ribosomal modifications (2′-O-methylations) alter protein synthesis.More specifically, the researchers are interested in the role played by ribosomes in cancer.

More particularly, they demonstrate that the plasticity of 2′-O-methylation modifies ribosome functioning. This discovery reveals a new facet of the ribosome, that of a direct regulator of protein synthesis, whereas up until now it was considered to be just an effector.

This research opens up new possibilities for using ribosomes, particularly in oncology. By providing a precise description, at the molecular level, of the ribosomes in the tumor cells of various cancers, this work opens up as yet unexplored research avenues for the identification of new prognostic markers of tumor development and for the development of new therapies targeted against these specific ribosomes. These avenues are currently being explored by the team from the Cancer Research Center of Lyon (CRCL).

[1] Marcel, V. et al. Cancer Cell. 2013. 24(3):318-30)

One Step Closer to Restoring Respiratory Function in Cystic Fibrosis?

© Fotolia

A new study by Olivier Tabary and his colleagues at the Saint-Antoine Research Center (Inserm Unit 938/Université Pierre et Marie Curie (UPMC), Sorbonne Universities) has revealed a new mechanism that makes it possible to restore the functioning of a cell channel found particularly in the lung mucosa of cystic fibrosis patients. This transfer, usually operated by the CFTR protein, is deficient in patients with cystic fibrosis and known for forming the basis of the disease. The findings, published in Nature Communications, open up the possibility of a therapy that would enable sufferers to recover their respiratory function.

Cystic fibrosis is a serious illness which affects digestive and pulmonary function, and affects 1 in every 4,500 newborns on average. Thanks to progress made by research, life expectancy has increased from a mere 5 years in 1960 to around 40, at present. This genetic disease is related to the deficiency of an extremely unstable gene, located on chromosome 7 which encodes a protein known as the cystic fibrosis transmembrane conductance regulator (CFTR). To date, over 2,000 mutations in this gene have been identified, making therapeutic approaches complicated.

Present in cell membranes of various mucous membranes (digestive system, lungs, etc.), the CFTR protein works as a channel transporting chloride ions into and out of cells. When the protein is deficient (following the mutation of the coding gene), the channel ceases to function. In the lungs, this brings about cycles of chronic infection and inflammation leading to the destruction of the pulmonary epithelium. The person will then present symptoms of cystic fibrosis.

Since the discovery in 1989 of the CFTR gene implicated in cystic fibrosis and the underlying genetic mechanisms, researchers have continued to further knowledge and propose new therapies. Nevertheless, these therapies have only been used in a small proportion of patients up until now, and with relatively weak effects. In 2008, the Anoctamin-1 (ANO1) chloride channel was identified for the first time. Given the deficiency of the CFTR protein in cystic fibrosis patients, the ANO1 channel was proposed as a therapeutic target for restoring chloride efflux.

 In a recent study published in Nature Communications and conducted by Olivier Tabary (Inserm Unit 938 Saint-Antoine Research Center), the researchers describe a regulation mechanism revealing the inhibitory effect of a microRNA (mirR-9) on the ANO1 channel.

With a therapeutic objective in mind, the team of researchers has succeeded in preventing miR9 from binding to ANO1 – thanks to the synthesis of a nucleic acid sequence. This makes it possible to stop microRNA inhibition of the chloride channel and restore its function.

 “Using this technique, we were able to restore chloride efflux, tissue distribution and mucociliary clearance in the cell lines of mice and cystic fibrosis patient cell cultures. These are all important parameters in the disease’s progression. Such a strategy would ultimately make it possible to target all patients with cystic fibrosis, regardless of their gene mutation, and correct major parameters in the development its pathophysiology,”  explains Tabary.

Further reading: Dossier d’information sur la mucoviscidose (in French)

A crucial enzyme finally revealed

© L. Peris /GIN

After 40 years of research, researchers at the CEA, the CNRS, the University of Grenoble-Alps, the University of Montpellier and the Inserm have finally identified the enzyme responsible for the tubulin cycle. Surprisingly, it is not one enzyme but two which control the cycle of this essential component of the cytoskeletal structure. This work opens up new prospects for the improved understanding of the role of tubulin, changes in the cycle of which are associated with cancers, cardiac diseases and neural disorders. These results were published on 16th November 2017 in the review Science.

A collaborative international project involving researchers from the CEA (French Atomic Energy Commission), the CNRS (National Centre for Scientific Research), the Inserm (French National Institute of Health and Medical Research), the University of Grenoble-Alps, the University of Montpellier and the University of Stanford[1] has identified an enzyme, Tubulin CarboxyPeptidase (TCP), which is responsible for the biochemical transformation of cellular microtubules, or detyrosination. Detyrosination is a biological reaction for the removal of the terminal amino acid tyrosine[2] from tubulin α, a constituent of microtubules. After four decades of research, biologists have succeeded in isolating this protein by purification, and have gone on to provide evidence of its cellular activity.

Microtubules contribute to essential cellular functions

Microtubules are dynamic fibres which are present in all cells. Formed by the combination of two proteins (tubulin α et tubulin β), microtubules assume numerous functions. They separate the chromosomes which are to be contained in the two daughter cells resulting from cell division, they contribute to the polarity of cells, morphology and cellular migration. They form “rails” upon which cellular constituents, such as proteins or RNA strands, are transported.

These cellular functions are regulated by the existence of “signals” which are present on the surface of microtubules. These signals are biochemical modifications to amino acids (described as post-translational modifications, as they take place after protein synthesis), executed by various enzymes which, in this case, modify the tubulins.

 The enzyme TCP, identified after 40 years of mystery

The activity of one of these enzymes was identified for the first time in 1977 by Argentine researchers, who named it “TCP” (Tubulin CarboxyPeptidase). The function of this enzyme, which had never been identified previously (its size and sequence were unknown) is the removal of the terminal amino acid, a tyrosine, from the end of tubulin α. This is the detyrosination reaction. A reverse enzyme, ligase TTL, is responsible for resetting this tyrosine in its place. This is tyrosination. This detyrosination/tyrosination cycle is vital for the cell and the organism. Massive (abnormal) detyrosination is observed in a number of severe cancers and cardiac diseases.

The identification and characteristic definition of TCP was therefore a major objective for understanding the physiological function of the detyrosination of tubulin α and evaluating the consequences of its inhibition.

In order to isolate TCP, researchers have monitored its activity, employing conventional biochemical techniques, and have involved chemists from the University of Stanford, who have developed a small inhibitor molecule for its activity. This molecule has been used as bait to “reel in” the desired enzyme.

Tubulin detyrosination/tyrosination cycle

Microtubules are fibres which are present in all cells, comprised of a stack of α/β tubulins. Tubulin carries a tyrosine (Y) at its end, which is alternately removed and replaced by two enzymes, thereby modifying the surface of microtubules. TCP (which is represented by a saw comprised of two elements, VASH/SVBP) is responsible for detyrosination. TTL (represented by a tube of glue) resets tyrosine on the tubulin. This cycle is essential to the various functions of microtubules in cells (division, migration, etc.) and is vital for the organism. © C. Bosc, GIN


scie TCP TCP saw
detyrosination detyrosination
tubuline tyrosinée tyrosinated tubulin
tubuline détyrosinée detyrosinated tubulin
tyrosination tyrosination
colle TTL TTL glue


Ultimately, not one, but two enzymes have been discovered. The latter, named VASH1 and VASH2, were already known to scientists, but it was not known that these were enzymes associated with the cytoskeleton. Researchers have demonstrated that, provided they are associated with a partner protein called SVBP, VASH1 and VASH2 are capable of the detyrosination of tubulin α. To demonstrate this, researchers have inhibited the expression of the former (or that of their partner SVBP) in neurons. They then observed a very strong decline in the rate of detyrosination of tubulin α, together with anomalies in the morphology of neurons (see Figure). Researchers went further, demonstrating that these enzymes are also involved in the development of the cerebral cortex.

Prospects for the fight against cancer

Thus, forty years after the conduct of the first work on the detyrosination of tubulin α, the enzymes responsible have been revealed. Scientists are now hoping that, by modulating the effectiveness of TCP and improving their knowledge of the detyrosination/tyrosination cycle, they can advance the fight against certain cancers, and achieve progress in the understanding of cerebral and cardiac functions.

Contrôle Control
VASH1 et VASH2 réduites VASH1 and VASH2 reduced
SVBP réduite SVBP reduced
Tubuline deTyrosinée / Tubuline Tyrosinée Detyrosinated tubulin / Tyrosinated tubulin

Photographs of the alteration of neurons associated with a reduction in the expression of TCP enzymes (VASH/SVBP). From left to right: control neuron, neurons in which the expression of VASH1 and VASH2 is reduced, neurons in which the expression of SVBP is reduced. Neurons with a reduced enzyme show a delay in development, together with morphological anomalies.

[1] The following institutes are involved: Grenoble Institute of Neurosciences, GIN (Inserm/Univ. Grenoble-Alps); Institute of Biosciences and Biotechnologies of Grenoble, BIG (Inserm/CEA/Univ. Grenoble-Alps); Institute of Advanced Biosciences, IAB (Inserm/CNRS/Univ. Grenoble-Alps), Department of Pathology, Stanford University School of Medicine (Stanford, USA), Institute of Human Genetics, IGH (CNRS/Univ. of Montpellier), Montpellier Centre of Cell Biology Research, CRBM (CNRS/Univ. of Montpellier).

[2] Tyrosine is one of the 22 constituent amino acids in proteins.

December 1, 2017: World AIDS Day

Friday December 1, 2017, is World AIDS Day.

Introduced by the World Health Organization in 1988 and observed in many countries each year since, this day aims to inform and raise awareness of the prevention, treatment and management of human immunodeficiency virus (HIV)/AIDS.

AIDS is a scourge that affects the world’s poorest countries and populations most particularly. In 2015, 37 million people[1] were living with HIV.

Big Killers: AIDS

Actively involved in research relating to the virus, Inserm researchers are mobilized all year round to find new strategies for its prevention, diagnosis and treatment.

Earlier this year, France hosted the 9th IAS Conference on HIV Science biennial gathering of the International AIDS Society. Inserm was one of the partners involved.

To find out more about recent INSERM/ANRS news on this topic:

[1] Source: WHO

The consumption of antioxidant-rich foods is associated with a lower risk of type 2 diabetes

A lower risk of type 2 diabetes has been observed among individuals consuming food rich in antioxidants. This effect is largely contributed by fruit, vegetables, tea and other hot beverages, as well as moderate consumption of alcohol, as shown in a recent study from an Inserm research group, published in Diabetologia, the journal of the European Association for the Study of Diabetes (EASD)

A diet rich in fruit and vegetables has previously been associated with a lower risk of certain cancers and cardiovascular conditions. An Inserm team (Health across generations, Center of Research in Epidemiology and Population Health, Villejuif, France) has now shown that such a diet is similarly associated with a reduced risk of type 2 diabetes.

The team already suspected there might be a link on the basis of previous studies showing that certain antioxidants, such as vitamins C and E, lycophenes or flavonoids, were associated with a reduction in type 2 diabetes risk. However, these studies looked only at isolated nutrients, not at the total antioxidant capacity of the diet. The researchers therefore wanted to verify whether overall diet, according to its antioxidant capacity, is associated with diabetes risk. Using data from the E3N cohort comprising French women recruited from 1990, then aged between 40 and 65 years, they followed 64,223 women from 1993 to 2008, all of whom were free from diabetes and cardiovascular disease at the time of inclusion in the study. Each participant completed a dietary questionnaire at the beginning of the study, including detailed information on more than 200 different food items. Using this information, together with an Italian database providing the antioxidant capacity of a large number of different foods, the Inserm researchers calculated a score for ‘total dietary antioxidant capacity’ for each participant. The group then analysed the associations between this score and the risk of diabetes occurrence during the follow-up period.

The results show that diabetes risk diminished with increased antioxidant consumption up to a level of 15 mmol/day, above which the effect reached a plateau. Increasing dietary antioxidants to this level could be achieved through eating antioxidant-rich foods such as dark chocolate, tea, walnuts, prunes, blueberries, strawberries or hazelnuts, to name just a few.

Women with the highest antioxidant scores had a reduction in diabetes risk of 27% compared with those with the lowest scores. ‘This link persists after taking into account all the other principal diabetes risk factors: smoking, education level, hypertension, high cholesterol levels, family history of diabetes and, above all, BMI, the most important factor’, clarifies Francesca Romana Mancini, the first author of this study. The foods and drinks that contributed the most to a high dietary antioxidant score were fruits and vegetables, tea and red wine (consumed in moderate quantities). The authors excluded coffee from the analysis, despite its high antioxidant levels, because the antioxidants in coffee have already been shown to be associated with reduced type 2 diabetes risk, and might therefore mask the effects of antioxidants from other sources.

‘This work complements our current knowledge of the effect of isolated foods and nutrients, and provides a more comprehensive view of the relationship between food and type 2 diabetes’ explains Guy Fagherazzi, the lead researcher in charge of diabetes research in the E3N study. ‘We have shown that an increased intake of antioxidants can contribute to a reduction in diabetes risk’. This now raises the question why: ‘We know that these molecules counterbalance the effect of free radicals, which are damaging to cells, but there are likely to be more specific actions in addition to this, for example an effect on the sensitivity of cells to insulin. This will need to be confirmed in future studies’, concludes Francesca Romana Mancini.

The E3N study (; Etude Epidémiologique auprès de femmes de la MGEN [Mutuelle Générale de l’Education Nationale]) is a prospective cohort study of around 100,000 French female volunteers born between 1925 and 1950, and followed from 1990. Since 1990, the women have completed and returned self-administered questionnaires every 2–3 years. The questionnaires cover their lifestyle and their  health status over time. The ‘lost to follow-up’ rate is very low because the MGEN is able to assist in following up non-responders.  The E3N study is supported by four founding partners: Inserm, la Ligue contre le Cancer, l’Institut Gustave Roussy and the MGEN. The E3N study is now continued via the E4N study (, a study awarded the status of  ‘Investment for the future’ (Investissement d’Avenir) in 2011 by the French National Research Agency (Agence Nationale de Recherche), and which aims to follow the children and grandchildren of the E3N participants, as well as the biological fathers of the children, with a view to studying the health of three generations of family members in relation to modern lifestyle.

Efficacy of online nutritional coaching in patients with type 2 diabetes and abdominal obesity


A study coordinated by Dr. Boris Hansel and Prof. Ronan Roussel, from the Diabetes-Endocrinology and Nutrition Department at Hôpital Bichat – Claude-Bernard, AP-HP and the Cordeliers Research Center (Inserm/Pierre and Marie Curie University, Paris Diderot, Paris Descartes University) shows that online nutritional coaching -an automated nutritional support program- improves dietary habits and glycemic control in patients with type 2 diabetes and abdominal obesity.

These results were published in the Journal of Medical Internet Research, JMIR on November 8, 2017.


Several nutritional coaching offers (personal support) have appeared on the internet in recent years, particularly in France. Whether a passing craze or a genuine revolution in nutritional management methods, online coaching is emerging as part of the treatment of chronic disorders. It is now being tested in certain hospitals, such as Hôpital Bichat-Claude Bernard, AP-HP, in order to achieve online support practically comparable to face-to-face contact.

Eating a balanced diet and taking appropriate regular physical exercise are the basis for treating type 2 diabetes and excess weight. However, for many diabetics, these recommendations are difficult to apply in the long term due to the lack of specific guidance in determining where efforts should be focused. While online support tools have been shown, in certain cases, to be effective, no French studies have tested online nutritional coaching to date, particularly for diabetes and/or abdominal obesity, in terms of reducing calorie intake and increasing physical exercise, resulting in weight loss similar to that achieved through hospital follow-up.

The research team tested a fully automated online coaching tool: the “Accompagnement Nutritionnel de l’Obésité et du Diabète par E-coaching – ANODE” [Diabetes and Obesity Nutritional Support Coaching] program developed by MXS. This program combines an electronic nutritional assessment and patient support in terms of diet and physical exercise. The researchers analyzed the utility of this program in patients with type 2 diabetes in a bicenter randomized trial.

The ANODE study was opened to 120 male or female volunteers, aged 18 to 75 years, with type 2 diabetes and overweight, particularly in the abdominal area, and having internet access.

Two groups were created: an investigational group benefiting from the ANODE automated online coaching program, and a control group receiving standard nutrition advice over a four month period.

The researchers monitored the changes in a diet quality score out of 100 (Diet Quality Index-International, calculated with a dietary diary over 3 days) between Study 1 (D-20 to D-2) and Study 2 (D100 to D118). At the same time, they measured the changes in “HbA1c or glycosylated hemoglobin”, i.e., hemoglobin which is chemically bound to glucose, cardiovascular risk factors, and physical aptitude (direct measurement of VO2max).

The two groups were comparable at baseline: 67% of females aged 57 years, with a BMI of 33 and diet index of 53.4/100 on average.

The results show that the diet index increased significantly in the online coaching group (+5.25 points) relative to the control group (-1.83) on average. The changes in food intake were more favorable in this group, with a reduction in fat, saturated fat, sodium and “empty calories” (calories provided by low-nutrient-dense foods).

Patient weight, waist measurement, and HbA1c also showed a more favorable reduction with this program. At least 5% weight loss is observed in 26% and 4% of subjects in the online coaching and control groups, respectively. The changes in plasma lipids and blood pressure are similar between the groups, and VO2max showed an identical increase in the two groups.

In conclusion, the online coaching program improved nutritional habits and glycemic control in patients with type 2 diabetes, in 16 weeks. It achieved its objective by significantly reducing weight and waist measurement. This program, which is adapted to patients, also has the advantage of being inexpensive as it is fully automated. These results thus encourage the development of online nutritional coaching in the follow-up of patients with type 2 diabetes.

The team is expected to initiate a national study on a larger scale next spring, over a one-year period, with an optimized connected health program. From January 2018, the AP-HP/Paris-Diderot University research team will be offering training in connected health, as part of the university diploma “Multidisciplinary practical training in connected health”.

World Diabetes Day


Celebrated every November 14 since its creation in 1991, World Diabetes Day is an opportunity to raise collective awareness of the condition and, above all, the resources deployed to manage it. Diabetes refers to consistently higher than normal blood sugar levels (hyperglycemia).  Two types of diabetes can be distinguished:

– Type 1, an auto-immune disease characterized by the insufficient production of insulin;

– Type 2, which occurs as the result of the poor use of insulin by the body.

Over half of deaths attributable to hyperglycemia occur before the age of 70. The World Health Organization (WHO) predicts that, in 2030, diabetes will be the 7th leading cause of death worldwide. Source: WHO

Last year, we showcased the research of Eric Renard, head of Inserm Unit 1191 “Determinants and correction of insulin secretion loss in diabetes”, which was working on the development of an artificial pancreas usable in daily life by people with type 1 diabetes.

Read last year’s C dans l’air (in French)

In late 2016, early 2017, studies performed in some thirty patients, along with three from Montpellier, demonstrated the feasibility of a 6-month trial. In addition, the opportunity to use new devices, particularly in Europe, is arising. One such device is an implantable continuous glucose monitoring system, which could be used for up to 6 months, and would replace the current system that requires changing every 7 to 10 days. This ongoing integration work will be consolidated in the first quarter of 2018, and concern three European centers: Montpellier, Padua and Amsterdam. Around 24 patients will be enrolled at each center in order to participate in this study funded by the NIH.

Probiotic Bacteria Produces Potent Analgesic


The intestinal microbiota still has surprises in store. The mode of action of a probiotic bacteria used in the symptomatic treatment of pain in irritable bowel syndrome has been revealed in a new study conducted by scientists from Inserm, Université de Toulouse and CHU de Toulouse [1] within the Digestive Health Research Institute (Inserm/INRA/Université Toulouse III – Paul Sabatier, ENVT). The bacteria produces a neurotransmitter (GABA) which, when bound to a lipid, crosses the intestinal barrier, acts on the sensory neurons located in the stomach, and reduces visceral pain. This new class of molecule, combining lipoprotein and GABA, could be used as a painkiller.

This research was published in Nature Communication.


Irritable bowel syndrome is a chronic disease characterized by abdominal pain associated with functional bowel disorders. This is a highly incapacitating disease which drastically reduces patient quality of life. Patients are powerless when faced with this syndrome, as no truly effective treatment exists for this disorder which affects 5% of the French population.

The probiotic bacteria Escherichia coli Nissle 1917[2], discovered during the First World War, was recently used as an orally administered alternative therapy for irritable bowel syndrome. Treatment with probiotics has become a popular trend given the “natural” characteristics of these products, and their supposed lack of toxicity. It is nonetheless essential to understand the molecular bases of their therapeutic properties. Research in this field examines and questions the origin of the bacterial factors behind these probiotic activities, and the validity of their use.

The scientists developed a project aiming to characterize the probiotic activity of the E. coli Nissle 1917 strain from this perspective. Their research shows that this bacteria produces GABA (gamma-aminobutyric acid) bound to an amino acid and a fatty acid. Together, these three molecules form a lipopeptide. GABA, the main nervous system inhibitory neurotransmitter, is then able to cross the intestinal barrier after the bacteria has bound it to this fatty acid. It can then bind to its receptor in order to diminish the activation of sensory neurons, and thus reduce pain. However, GABA cannot cross the intestinal barrier on its own (without its fatty acid).

Once the lipopeptide was identified and characterized, initial studies were first conducted on cultured murine sensory neurons. Exposing these neurons to capsaicin (the active substance of chili peppers) increased calcium flow, which is characteristic of the neurons’ hypersensitivity, compared to the control neurons. These changes in calcium flow are not observed in these neurons when they are pretreated by adding synthetic lipopeptide to the culture medium.

These studies were then conducted on mice. Electrodes placed on the animals were able to measure the intensity of abdominal contractions characteristic of pain (equivalent to stomach cramps in man). Once they ingested the synthetic lipopeptide, the abdominal contractions in the hypersensitive mice then became equivalent to those observed in the control mice.

This study has made it possible to file a patent for a new class of molecules that can be used as analgesics. “As these do not modify intestinal motility or physiology, we also hope that they will generate fewer side effects than morphine, for example. This should evidently be validated by future therapeutic trials,” states Nicolas Cenac.

This discovery demonstrates the importance of having a better understanding of the modes of action of the probiotics currently in use, and the therapeutic potential of lipopeptides produced by the intestinal microbiota.

Inserm Transfert has filed a patent application for this research.


[1] A team of physiopathologists and a team of bacteriologists from the Toulouse Digestive Health Research Institute (IRSD) (Inserm/INRA/Université Toulouse III – Paul Sabatier, ENVT) and teams of chemists from the Institute of Biomolecules Max Mousseron in Montpelier and the Metatoul network in Toulouse


[2] Named after the German physician Alfred Nissle who isolated this strain from a stool sample obtained from a soldier in the First World War, who was the only member of his unit that did not get dysentery.