The role of the microbiome in type 2 diabetes

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The role of the microbiome in type 2 diabetes Expert Forum on diabetes: Genetics, nutrition and the future of diabetes management 10 October 2017 Luc Sterkman, MD CEO Caelus Health

Bugs in daily life Good guys and bad guys

Bugs in daily life Total surface of appr. 30 m2 Number of human cells is equal to Number of bugs

Bugs in daily life Good guys in our food

The stage is set, the world knows: No longer «the best microbe is a dead microbe» Scientists Global opinion makers Business https://www.sciencenews.org/ http://www.economist.com/ August 16, 2012 http://www3.weforum.org/ Commensals as next generation probiotics, mentioned by all as important lever Large public and private investments!! 5

Bugs as drugs Restoring the balance

Bugs as drugs Good guys to be added Maintaining a stable and healthy environment

FECAL TRANSPLANTATION Research tool and basis for Therapeutic interventions 3 The stool can be applied into the small intestine via a The tube stool trough can be the applied nose or into mouth the small (a) intestine or deep via into a tube through the nose or mouth (a) or deep into the colon, using colonoscopy (b). Enemas are the colon, using a colonoscopy (b). Enemas are popular popular for for at-home at-home treatments, treatments, but but they they only only reach reach the lower the lower end of end the colon of the (c) colon (c). 1 In In a fecal transplant, stool from from a healthy a donor is used to replace a a patients patient s gut gut microbial flora 2 Exact preparation vary, Exact preparations vary, but but usually the stool is usually the stool is blended blended with saline with and saline put through and out a strainer. trough It a can strainer. be frozen It can before use. frozen before use. a b In the future, scientists hope to replace fecal transplants with In the an future, odorless scientists mix hope of bacterial to replace strains fecal derived transplants from with human stool, odorless grown mix of in bacterial the lab. It strains could derived be applied from human using existing stool, frown methods in the or lab. It could be applied using existing methods or in capsules. in capsules. 4 c

Bugs as drugs Restoring the balance

New field is emerging Microbiota based products, both for prevention and treatment A highly innovative and rapidly growing field Various approaches: - FMT as intervention - Consortia of commensal micro-organisms - Purified products based on 1 individual micro-organism Investments in new ventures in past decade > 1 bio$ From gastro-intestinal into new clinical areas

Risks in life

Diabetes mellitus Global pandemic of obesity and Diabetes mellitus Huge burden for both individuals and society Strong need for early intervention

The Personalized Nutrition Project Courtesy to Dr Eran Segal

The Personalized Nutrition Project

The Personalized Nutrition Project

The Personalized Nutrition Project

The Personalized Nutrition Project

The Personalized Nutrition Project

Foundation of Day Two

Bugs against diabetes Fecal transplant study Metabolic syndrome is also shortly referrred to as pre-diabetes People with pre-diabetes Improved sensitivity for insulin Identification of key bugs -> publications -> patents

DIME STUDY RESULTS - SAFETY & EFFICACY -2- Metagenomics analysis of the DIME study shows - Significant increase in insulin sensitivity (Rd) - Close to significant increase in Rd change Number of responders increased from low dose (2/9) to high dose (5/9). Implicates further selection of subjects in future studies and/or stratification for diversity and/or baseline levels of microbiota used as intervention.

REGULATORY PROCESS Food first applications Nutrition/functional food EU EFSA FSMP Health claim article 14.1 Health claim article 13.5 USA Structure/function claim Qualified Health claim Pharma second generation

Innovative approach Prevention may initially increase costs, while reducing costs at later stages SCIENTIFIC ADVISOY BOARD DE VOS, NIEUWDORP PRELINICAL & MICOBIOLOGY LABS New buzz-words LINICAL are: RESEARCH FACILITIES e-health, mobile health, telemedicine, assisted living, and bugs as drugs

Bugs in health 2.0 SCIENTIFIC ADVISOY BOARD DE VOS, NIEUWDORP Individual testing of your own microbiome PRELINICAL & MICOBIOLOGY LABS LINICAL RESEARCH FACILITIES www.mymicrozoo.com based in Leiden! Subsequent change in lifestyle and/or taking probiotics (or FMT)

Bugs in health 2.0 SCIENTIFIC ADVISOY BOARD DE VOS, NIEUWDORP Integrated approach PRELINICAL & MICOBIOLOGY LABS Combination of LINICAL - Diagnostics RESEARCH FACILITIES - Prevention (food) - Therapy (medication)

Summary take home messages Bugs are abundantly present in our body and daily environment Bugs include good guys and bad guys Health is based on a balance of microbiota Disease may be caused by a dysbalance in the bugs Bugs may act as powerful drugs and restoring the balance This works for gastro-intestinal problems Obesity and Diabetes are rapidly increasing Urgent need for prevention / early intervention Microbiota increase insulin sensitivity in MetS Microbiota may delay the onset of diabetes Further research is ongoing huge potential Microbiota fit in an integrated approach

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