Metazoans carry dynamic microbial communities on their mucosal surfaces with which they establish complex reciprocal interactions. These interactions contribute to many aspects of normal host physiology. In the gut, these microbial communities called the microbiota enhance digestive efficiency by providing metabolic activities aiding their hosts in maximizing extraction of dietary energy. In addition, the gut microbiota both promotes proper immune system development, local immune homeostasis and limits pathogen colonization (fraune2010). In return, the microbiota derives benefit from the association with its host by inhabiting a nutrient rich environment, the host providing “le gîte et le couvert” (i.e. “board and lodging”). This mutually beneficial or mutualistic interaction relies on a homeostatic host/microbiota relationship which depends on two main parameters: the intrinsic capacity of microbes to colonize and persist in its host and the host’s ability to tolerate and control them. When deregulated this relationship may result in pathological outcomes such as episodic infectious diseases, chronic inflammatory diseases, metabolic disorders or even some forms of cancer.
It has been known for decades that humans carry ten times as many bacterial cells as their own cells but characterization of the intestinal microbiota was hampered by the difficulty of cultivating most gut bacteria species in the laboratory. Thanks to the revolution in sequencing technologies the composition of commensal bacteria communities and their collective genome (microbiome) are now starting to be unravelled. These massive sequencing efforts start to shed light on this complex ecological system. Indeed, hundreds of different bacterial phylotypes inhabit the human gastro-intestinal tract and their relative proportions are influenced by environmental factors and host genotype. The analysis of human microbiomes has now revealed that such communities encode about 150 times as many genes as the human gene complement. Of note, microbiomes show a significant enrichment in genes encoding metabolic activities. Hence, the idea that the intestinal microbiota constitutes an additional organ has recently re-emerged. Despite this renewed interest and in part because of the complexity of the system, a clear view of the physiological benefits associated with host/microbiota relationship remains elusive. Hence, the molecular mechanisms through which the microbiota exerts its beneficial influence are still largely undefined. Our research program addresses these caveats.
Elie Metchnikoff first introduced the concept of a beneficial role played by intestinal bacteria in 1903. He suggested that it would be possible to modify the gut flora and to replace harmful microbes with useful ones. He took up the study of the flora of the human intestine and developed a theory that senility is due to poisoning of the body by the products of certain of these bacteria. To prevent the multiplication of these “harmful” organisms he proposed a diet containing milk fermented by bacilli, which produce large amounts of lactic acid and for a time this diet became widely popular. His inspiring work was followed by Japanese scientist Minoru Shirota who begun to investigate the causal relationship between bacteria and good intestinal health, which eventually led to the worldwide marketing of Kefir and other fermented milk drinks and nowadays probiotic alimentary complement. The World Health Organization has defined probiotics as “Live microorganisms which when administered in adequate amounts confer a health benefit on the host". They correspond to selected strains of bacterial species of the Lactobacillus and Bifidobacterium genera commonly found in the human and animal intestinal tracts. Because of the current increased incidence of atopic, metabolic and intestinal inflammatory diseases in western country populations, and the emerging link between these pathologies, nutrition and intestinal microbiota composition and activity, probiotics potentials to treat these syndromes are being revisited. However there is an evident paucity of functional evidence on the benefits associated with these alimentary complements. Indeed, despite intense marketing campaigns by agroalimentary and pharmaceutical companies advertising the beneficial effects of probiotics on human and animal health, the European Food Safety Authority (EFSA) has so far rejected most claims on probiotics benefits in Europe due to insufficient research and no conclusive proofs.
This scarcity of experimental evidence highlights the need for revisiting probiotic physiological benefits and to invest research effort in the accumulation of basic knowledge about beneficial host/intestinal bacteria relationships. In this light, the use of experimental animal models to evaluate and clarify the impact of intestinal bacteria towards their host physiology should be of great help.