Production of PUFA-derived metabolites by the gut microbiota

More and more evidence show that the trillions of bacteria housed in the gastro-intestinal tract, and called the gut microbiota, are able to influence host physiology, namely by producing bioactive metabolites prone to regulate host metabolism. Due to the very high metabolic potential of the gut microbiota, a near infinite metabolic potential could be envisaged, in addition to the well known short-chain fatty acids, bile acids, or choline-derivatives. In this doctoral thesis, we proposed that polyunsaturated fatty acid (PUFA)-derived metabolites could be a new kind of bioactive metabolites produced by the gut microbiota. This hypothesis is supported by in vitro studies performed with isolated gut bacteria, mainly Bifidobacterium spp., Lactobacillus spp. and Roseburia spp., which are able to produce CLA (conjugated linoleic acid) and CLnA (conjugated linolenic acid) or other non-conjugated metabolites such as vaccenic acid. Our experimental work provides evidence that the gut microbiota is able to produce, in vivo, PUFA-derived metabolites. Modulations of the gut microbiota composition, by high-fat diet feeding or prebiotic supplementations, change its ability to produce these metabolites. Furthermore, we highlight that both the type and the quantity of substrate (PUFA) available in the gut for bacterial metabolism also influence the profile of PUFA-derived metabolites produced by the gut microbiota. Furthermore, we show that the main production site of these metabolites is the distal part of the gut (i.e. the caecum and colon). Even if PUFA-derived metabolites are accumulating in intestinal tissues, our studies reveal that their systemic availability remains limited, suggesting that their relevance in host metabolism regulation would be of most importance at the intestinal level. In complement of the experimental work performed on mice models, we have the opportunity to use human samples obtained during a prebiotic-intervention on obese individuals. No major modifications of the fatty acid profile, including PUFA-derived metabolites, were observed between the beginning and the end of both treatments (prebiotic and placebo) and between placebo-treated and prebiotic-treated patients. However, we highlighted interesting correlations between specific CLA and CLnA and some bacteria (for example Bifidobacterium spp. and Lactobacillus spp.) known to be able to produce these metabolites in vitro from fatty acid, supporting the production of PUFA-derived metabolites by the gut microbiota in human. Our experimental data underline the importance to further pay attention to unknown metabolites produced by the gut microbes, when evaluating host-gut microbiota interactions in human health.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 201