Human microbiomes

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As soon as multicellular beings appeared on earth, they were colonized by microbes, the first inhabitants of the biosphere. The relevance and robustness of the human-microbe symbiosis is therefore the fruit of a billion years of microbe-eukaryote multicellular coevolution. The term "symbiosis" was introduced by Anton de Bary in the 19th^centuryas the rule of life shared by several species, "the living association of different species". The symbiotic association is often built around a large partner, the host, and smaller partners, the symbionts. This view is highly subjective, as in the human-microbe symbiosis, microbes far outnumber humans in terms of cells (× 10) and genes (× 150).

In this symbiotic, largely mutualistic relationship, bacteria benefit from a stable environment (temperature, oxygen, pH, nutrients). The host gains a broad spectrum of digestive, metabolic and nutritional capacities, protection against the intrusion of allogenic/pathogenic microorganisms (barrier effect), controlled stimulation of mucosal and systemic immunity, and even other functions whose diversity is beginning to be recognized.

Each body site corresponds to a specialized ecological niche, characterized by its own microbial consortia, different community dynamics and close interactions with tissues. The most studied of human microbial consortia is the intestinal microbiota. It is extremely diverse in terms of taxonomic, genetic and functional biodiversity.

Although recognition and study of the microbiota began in the late 19th^centuryand continued through the first half of the 20th^centurywith researchers such as Theodor Escherich, Elie Metchnikoff, Theobald Smith, Arthur Kendall and Theodor Roseburry, it largely took a back seat to the work of Louis Pasteur and Robert Koch and their respective schools on pathogenic microbes. It wasn't until the 1960s that the essential properties of the intestinal microbiota were established: its composition by hundreds of often uncultivable species, largely dominated by anaerobic species; its establishment in the infant according to a pattern of "ecological succession"; its obedience to ecological laws controlled by environmental factors, the host and the bacterial populations themselves. This gave rise to the notion of an additional organ. The 1980s saw the application of molecular identification methods, in particular the sequence of variable portions of the genes encoding ribosomal RNA16S, which made it possible to move away from conventional culture methods, enabling us to assess the diversity of species making up the microbiota, the stages of its establishment and its resilience in the presence of antibiotics. More recently, the spectacular advances in next-generation sequencing and bioinformatics have made it possible to replace the concept of "microbiota" with that of "microbiome", i.e. the pool of all the microbiota's genes, its constants and variables. This descriptive metagenomics has made it possible to further assess the extreme diversity of the microbiota. It can also be correlative: notion of enterotypes, correlation between impoverished diversity and pathologies. Finally, it can be analytical, as described in the following lectures.