[The human intestinal microbiota]

Abstract

The human intestinal microbiota constitutes a complex ecosystem which is now well recognized for its impact on human health and well-being. It contributes to maturation of the immune system and provides a direct barrier against colonization by pathogens. Its possible implication in diseases of modern societies, currently increasing in prevalence, has been reported. These include allergies, inflammatory bowel diseases and possibly metabolic and degenerative disorders. The analysis of the molecular composition of the human intestinal microbiota indicates marked inter-individual variations which may seem paradoxical considering the high degree of conservation of major functions of the intestinal microbiota such as anaerobic digestion of alimentary fibres. We have characterized a phylogenetic core within the human intestinal microbiota, in terms of composition, i.e., a set of conserved species that could be responsible for major conserved functions. Based on culture-independent molecular assessments, current knowledge enables a definition of criteria qualifying the normal state of the human intestinal microbiota that we call normobiosis. This further enables the identification of specific deviations from normobiosis, i.e., dysbiosis in immune, metabolic or degenerative diseases. Notably, Crohn's disease, an inflammatory bowel disease of yet unknown aetiology, is associated with intestinal dysbiosis with a lower representation of the Clostridium leptum group among the Firmicutes phylum. We further showed that the bacterial species Faecalibacterium prausnitzii exerts anti-inflammatory properties in vitro and in animal models; this could explain its ability, when detected in the mucosa-associated microbiota of patients in vivo, to protect patients from post-operative recurrence of endoscopic signs of inflammation 6 months after surgical resection of the ileocecal region of the gut. By confirming the major role of the microbiota in bowel-related disorders, which are especially associated with a disruption of homeostasis, we are currently applying high throughput functional metagenomic screens in order to identify signal molecules and mechanisms of bacteria-host cross-talk. Together with the high resolution description of the human intestinal metagenome, as well as explorations of environmental proteins and metabolites, these observations will further our understanding of the functional roles bacteria play in the maintenance of health and well-being in humans. It will open new perspectives for the monitoring and design of strategies for modulating the microbiota for health.