Les enjeux du microbiote pour la médecine de demain. L’appel des spécialistes nationaux et internationaux pour mieux accompagner la révolution en marche (Dr Irène Drogou, Le quotidien du Médecin)
Mais avant d’aller vers une médecine de précision, il manque l’essentiel : l’outil n’est pas standardisé et il faut définir des marqueurs prédictifs pour stratifier les patients. De nouvelles cibles thérapeutiques originales, notamment via ses métabolites, restent à identifier. Peu importe, le phénomène de mode s’est emballé, les médias suscitent un intérêt sans précédent dans le public et une véritable jungle de probiotiques en tout genre fleurit sur le net et en parapharmacie.
Pour qu’une vraie révolution médicale devienne possible, la standardisation de l’analyse du microbiote est essentielle, la clarification de la réglementation incontournable, abondent en ce sens les communautés académiques et scientifiques. Un groupe de travail avec les personnalités les plus en pointe du domaine a planché sur le sujet le 20 octobre 2017 à Paris lors d’un colloque international, organisé par l’Académie de médecine et sous le parrainage de l’Organisation mondiale des Académies de médecine (IAP), avec la participation de l’International Human Microbiota Consortium (IHMC), de l’International Society of Microbiota (ISM) et de la World Gastroenterology Organization (WGO).
Pour le Dr David Bjorkman, gastro-entérologue à la faculté de médecine de l’Utah et président de la WGO : « Les patients me demandent quel probiotique prendre car beaucoup sont en vente libre, partout. Sur le net, on retrouve environ 300 000 marques. Mais je ne sais pas lequel est le meilleur pour eux. On n’a pas encore les réponses à la question de savoir quelles bactéries sont bonnes ou mauvaises pour telle ou telle personne ».
Pour quelques centaines d’euros, il est possible aujourd’hui de faire son profil de microbiote. « Des collègues gastroentérologues voient des patients leur amener leurs résultats en consultation, explique Joël Doré. En l’absence de standard reconnu, on ne peut rien en faire, c’est dommage. Un contrôle académique et scientifique est nécessaire. »
La réflexion n’en est pas à ses débuts et l’IHMC a déjà fait un gros travail d’évaluation, de « benchmarking » des différentes méthodes utilisées dans les laboratoires de recherche. En 2015, le consortium a mis en ligne en accès libre des standards pour le séquençage massif. « L’idée est d’aller vers un partage des big data sur le métagénome, explique le Pr Doré. Pour raconter les mêmes histoires, il faut que les données soient suffisamment standardisées pour être comparables. »
De la collecte des échantillons de selles, au séquençage ADN en passant par l’extraction de l’acide nucléique, sans oublier la bioinformatique et la biostatistique, « chaque étape doit être standardisée », renchérit le Pr Karine Clément, spécialiste nutrition à l’hôpital de la Pitié-Sapêtrière (APHP), ex-directrice du centre d’excellence ICAN et directrice de recherche INSERM.
Sur le terrain, les pratiques peuvent être très hétérogènes, comme l’a constaté Joël Doré, qui a participé à ce travail d’évaluation pour l’IHMC. « Hormis pour la bioinformatique, il existe de grosses, grosses différences, explique-t-il. Pour l’extraction de l’ADN, sur les 20 labos évalués, les résultats n’étaient pas terribles pour la moitié. Des processus suboptimaux sont des biais importants de recherche. L’impact attendu de ces standards est très fort. »
Enjeux éthiques et politiques
Le recueil de données cliniques est sans doute le plus difficile à standardiser. « Les méthodes pour mesurer la masse grasse, par exemple, diffèrent d’un pays à l’autre, explique Karine Clément. Le recueil des données alimentaires est déjà en soi très compliqué, alors d’un pays à l’autre, ça l’est davantage encore. » Seulement 14 items ont finalement été retenus. Pour pallier cette lacune, l’IHMC invite chaque équipe à collecter un maximum de données.
De plus, si la règle est de partager les données dès publication pour la métagénomique, il n’en est pas de même pour les données cliniques, dont le niveau de protection est fixé dans le protocole de l’essai. « Il y a de vrais enjeux éthiques et politiques », estime le Pr Clément.
Les procédures de l’IHMC ont été téléchargées plusieurs millions de fois sur le site. « L’usage va être déterminant, souligne le Pr Joël Doré. Notre démarche n’est pas d’établir des normes, mais de proposer des standards partagés pour avancer. Il faut savoir respecter le besoin naturel de liberté de vue et d’esprit. »
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