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Newsletter June 2019

Newsletter June 2019

by Dr Maxime Prost "France Medical Affairs Director" / Camille Aubry, PhD "International Medical Affairs Manager"

Dear readers, according to the World Health Organization, certain digestive cancers (stomach, oesophagus, liver and colorectal) accounted for 23.8% of new cancers diagnosed worldwide in 2018. Colorectal cancer alone caused nearly 900,000 deaths globally last year. Although it has long been known that diet has an undeniable influence on the occurrence of digestive tumours, the related link between these diseases and the gut microbiota has been advanced more recently. This has led to a paradigm shift in which cancer is now considered to be a disease with a strong environmental component. Runaway fervour or fundamentally true? If one believes the scientific literature – which mirrors the evident international craze – the second option could well bring its share of discoveries.

Recent preclinical and clinical research provides evidence for the links that the scientific community has suspected: how some Fusobacterium species could stimulate the development of a pro-inflammatory environment in the gut mucosa and promote the emergence and progression of colorectal tumours; how Helicobacter pylori – like other bacterial species and together with multiple factors – could promote gastric tumours; or how the intestinal microbiota could modulate the antitumor immune response. In other words, intestinal dysbiosis would be implicated in the entire tumour process, from pathogenesis to the response to chemotherapy and immune checkpoint inhibitor treatments.

Professor Iradj Sobhani (Université Paris-Est Créteil and Henri-Mondor University Hospital, Créteil, France) sheds some light on this latter point in particular. He describes current evidence showing that the intestinal microbial community, as a whole, metabolizes anticancer drugs like gemcitabine and lowers its efficacy, and also influences the effects of ionizing radiation treatments and postoperative healing. He also mentions the deleterious effects of antibiotic therapy underlying the variability of response to anti-PD-1 and anti-PD-L1 immunotherapies in patients with metastatic cancer. A review that highlights the importance of the intestinal microbiota as a factor of personalized medicine in the booming field of immuno-oncology.

Microbiology and oncology go hand in hand in this issue. An occasion for Professor Harry Sokol (Hôpital Saint-Antoine, Paris, France) to revisit an article published in Science Translational Medicine showing that autologous faecal microbiota transplantation could find a promising application in haematology. As far as patient benefits go, Professor Emmanuel Mas (Hôpital des Enfants, Toulouse, France) unveils an effective dietary treatment that is well tolerated in patients with Crohn’s disease.

Enjoy your reading.

DIGESTIVE CANCERS AND INTESTINAL MICROBIOTA: FROM ONCOGENESIS TO RESPONSE TO TREATMENT

by Prof. Iradj Sobhani - Gastroenterology, Université Paris Est Créteil (UPEC) and Henri Mondor University Hospital, Créteil, France

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With an increasing prevalence that has made it the leading cause of death in many western countries, cancer is now regarded more as an emergent disease arising from environmental factors than a disease caused by constitutional genetic aberrations, which are now known to be much less common than previously thought. A paradigm shift favoured by the development of molecular biology techniques, a better understanding of the underlying mechanisms and the identification of associated biomarkers. For several decades, epidemiologists have observed a connection between cancer and diet, which has made the intestinal microbiota – and thus dysbioses – a focal point in the study of cancer. This connection has now found a mechanistic explanation involving energy metabolism, inflammation and immunity: influenced by diet, some bacteria can affect tumour progression, the response to cancer treatments and the side effects of these treatments.

RECONSTITUTION OF THE GUT MICROBIOTA OF ANTIBIOTIC-TREATED PATIENTS BY AUTOLOGOUS FAECAL MICROBIOTA TRANSPLANT

by Prof. Harry Sokol - Gastroenterology and Nutrition, Saint-Antoine Hospital, Paris, France

Vignette

Antibiotic treatment can deplete the commensal bacteria of a patient’s gut microbiota and, paradoxically, increase their risk of subsequent infections. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), antibiotic administration is essential for optimal clinical outcomes but significantly disrupts intestinal microbiota diversity, leading to loss of many beneficial microbes. Although gut microbiota diversity loss during allo-HSCT is associated with increased mortality, approaches to re-establish depleted commensal bacteria have yet to be developed. A randomized, controlled clinical trial has been initiated to compare autologous faecal microbiota transplantation (auto-FMT) versus no intervention; the intestinal microbiota profiles of 25 allo-HSCT patients (14 who received auto-FMT treatment and 11 control patients who did not) were analysed. Changes in gut microbiota diversity and composition revealed that the auto-FMT intervention boosted microbial diversity and re-established the intestinal microbiota composition that the patient had before antibiotic treatment and allo-HSCT. These results demonstrate the potential utility of faecal sample banking for auto-FMT for posttreatment remediation of a patient’s gut microbiota after microbiota-depleting antibiotic treatment during allo-HSCT.

TREATMENT OF ACTIVE CROHN’S DISEASE WITH AN ORDINARY FOODBASED DIET THAT REPLICATES EXCLUSIVE ENTERAL NUTRITION

by Prof. Emmanuel Mas - Gastroenterology and Nutrition Department, Children’s Hospital, Toulouse, France

Vignette

Exclusive enteral nutrition (EEN) is the only established dietary treatment in Crohn’s disease (CD), but its acceptability is limited. There is a need for new dietary treatments for CD.

The effects of a personalized diet (CD-TREAT), based on the composition of EEN, were evaluated by analysing the intestinal microbiota, inflammation and clinical response in rats, in healthy adults, and in children with relapsing CD.

Ultimately, it was shown that CD-TREAT replicates EEN changes in the gut microbiota, decreases gut inflammation, is well tolerated and is potentially effective in patients with active CD.

To read the full article:
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THE IMPACT OF THE PARENTS’ MICROBIOME ON THE DESCENDANTS’ HEALTH

by Prof. Markku Voutilainen - Turku University Faculty of Medicine; Turku University Hospital, Department of Gastroenterology, Turku, Finland

Infant gut is colonized by maternal vaginal and fecal bacteria during vaginal birth. Microbial colonization of the gut starts during fetal life, although its role remains debatable. The hypothesis of developmental origins of health and disease (DOHaD) suggests that the conditions during fetal life have an impact on the early life of the newborn and also result increased risk for chronic diseases of the offspring.

ESOPHAGEAL MICROBIOME – THE CAUSE OR CONSEQUENCE IN ESOPHAGEAL DISEASES?

by Prof. Markku Voutilainen - Turku University Faculty of Medicine; Turku University Hospital, Department of Gastroenterology, Turku, Finland

Gastroesophageal reflux disease is common in western world. Barrett’s esophagus (BE) is the complication of reflux disease and the major risk factor of esophageal adenocarcinoma, which has a five-year survival rate less than 20%.

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Report from the conference

JFHOD

Paris - France

The Journées francophones d’hépato-gastroentérologie et d’oncologie digestive (French language Hepatogastroenterology and Digestive Oncology Congress) was held in Paris from 21 to 24 March 2019, with an attendance of more than 5,000 French-speaking doctors and researchers. A number of original studies on the intestinal microbiota (IM) were presented.

Gut Summit

Miami - USA

During its 8th edition last March, the GMFH devoted considerable place to diet and the way it interacts with the gut microbiome, preventing or promoting diseases.

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