The human gut microbiome as source of innovation for health: Which physiological and therapeutic outcomes could we expect?

Abstract

From the moment of birth, each human being builds a microbe-host symbiosis which is key for the preservation of its health and well-being. This personal symbiotic coexistence is the result of progressive enrichments in microorganism diversity through external supplies. This diversity is nowadays massively overthrown by drastic changes related to clinical practice in birth management, environmental exposure, nutrition and healthcare behaviors. The last two generations have been the frame of massive modifications in life and food habits, with people being more and more sedentary, overfed and permeated with drugs and pollutants. We are now able to measure the impact of these changes on the gut microbiota diversity. Concomitantly, these modifications of lifestyle were associated with a dramatic increase in incidence of immune-mediated diseases including metabolic, allergic and inflammatory diseases and most likely neurodegenerative and psychiatric disorders. Microbiota is becoming a hot topic in the scientific community and in the mainstream media. The number of scientific publications increased by up to a factor three over the last five years, with gastrointestinal and metabolic diseases being the most productive areas. In the intellectual property landscape, the patent families on microbiota have more than doubled in the meantime. In parallel, funding either from National Institutes (e.g. from NIH which funds research mainly in the field of allergies, infections, cancer and cardiovascular diseases, from the White House which launched the national microbiome initiative) or by pharmaceutical companies follow the same trend, showing a boost and a strong support in the research field on microbiota. All major health players are investing in microbiome research as shown by the number of deals signed and by funding during 2015. The Giens round table addressed how the medicine of tomorrow, considering human beings as a human-microbe symbiotic supraorganism, could leverage microbiome knowledge and tools. The rationale for our working group has been structured around four domains of innovation that could derive from ongoing efforts in deciphering the interactions between human cells and intestinal microbiome as a central component of human health, namely: (1) development of stratification and monitoring tools; (2) identification of new target and drug discovery, as a part of our supra-genome; (4) exploitation of microbiota as a therapeutic target that can be modulated; (4) and finally as a source of live biotherapeutics and adjuvants. These four streams will exemplify how microbiota has changed the way we consider a wide range of chronic and incurable diseases and the consequences of long-lasting dysbiosis. In-depth microbiota analysis is opening one of the broadest fields of investigation for improving human and animal health and will be a source of major therapeutic innovations for tackling today's medical unmet needs. We thus propose a range of recommendations for basic researchers, care givers as well as for health authorities to gain reliability in microbiome analysis and accelerate discovery processes and their translation into applications for the benefits of the people. Finally, les Ateliers de Giens round table on microbiota benefited from the richness of the French ecosystem. France represents a center of excellence in the microbiota research field, with French institutions as Institut national de la recherche agronomique (INRA [Metagenopolis, Micalis]), Centre national de la recherché scientifique (CNRS), Unité de recherche sur les maladies infectieuses et tropicales émergentes (URMITE), Institut of Cardiometabolism and Nutrition (ICAN), Institut des maladies métaboliques et cardiovasculaires (I2MC), Institut national de la santé et de la recherche médicale (Inserm), Pasteur Institute and Gustave-Roussy being top-players for the number of publications.

Keywords: Biomarkers; Chronic pathologies; Dysbiosis; Live Biotherapeutics; Metagenome; Microbiodata; Prebiotics; Synbiotics.