Lessons to Be Learned from Clinical and Experimental Research on the Intestinal Microbiota Metabolic Activity for Health Benefit and Perspectives

Abstract

Although there is no doubt that numerous metabolites produced by the bacteria from alimentary compounds in the intestinal fluid are active, either positively or negatively, on the colon epithelium in terms of renewal, barrier function, energy metabolism, and physiology, we need additional information on the concentrations of bacterial metabolites in their active form in the vicinity of colonic epithelium and on the effects of mixtures of these compounds on this structure. Many active bacterial metabolites have been shown to be implicated in microbial communication, serving notably as signaling molecules implicated in bacterial physiology and growth. If bacteria can provide compounds such as some vitamins and amino acids to the host, the exchange of substrates is largely orientated toward supply by the host of substrates from alimentary origin to the intestinal microbiota for their metabolic and physiological needs. Several intermediary and metabolic end products produced by the intestinal bacteria can cross the intestinal epithelium, with a part of them being utilized and transformed in the epithelial cells during their transcellular journey. The compounds released in the portal blood can then be further transformed in the liver, giving rise to co-metabolites. Although several among bacterial metabolites and co-metabolites have been shown to be beneficial for some host tissues in different physiological and pathophysiological situations, the same compounds may prove to be deleterious on other tissues, leading to consider effects of these compound according to the host tissues and to the physiological or pathophysiological context. Additional studies are urgently needed concerning the metabolic and physiological relationships between mammals and their microbiota. These studies should include mechanistic studies regarding for instance the processes implicated in the transport of active bacterial metabolites from the luminal fluid to the bloodstream, the enzymatic processes that allow synthesis of co-metabolites in mammalian tissues, as well as entry of these compounds within the target tissues. Dietary intervention in volunteers in different situations is also crucially needed to better consider the microbial-host metabolic communication in both preventive and curative perspective.