Serguei Fetissov

– Abstract –

Gut bacteria and host feeding behavior

Feeding behavior is driven by visceral feelings of hunger and satiety. Their daily changes follow the stable rhythms consisting of about 20 min of satiation after beginning of a meal and 5 hours of satiety before felling of hunger triggering the onset of a next meal. The regularity of appetite changes is fundamental for structuring daily human activity. While several hormonal and neuronal circuitries are known to regulate feeding behavior, recent data also support a fundamental role of gut bacteria (1). In fact, when animals eat they also feed the numerous bacteria inhabiting their gastro-intestinal tract. Such bacterial feeding occurs both immediately after nutrient ingestion as well as several hours later after the intestinal transit of non-absorbed fibers. Indeed, as for the process of digestion, food intake triggers a pavlovian reflex of intestinal secretion setting-up the timing of the hormonal and metabolic changes with resulting rhythms of feeding behavior. Providing nutrients to bacteria triggers their growth which undergoes a specific dynamic under conditions of a regular nutrient provision and rich bacterial density in a limited volume such as in the lower gut. These dynamics include an immediate bacterial duplication lasting for 20 min before the onset of the bacterial stationary phase. E.coli grown in such conditions, imitating the daily feeding rhythms in humans, produces bacterial proteins which reduce food intake and activate intestinal satiety pathways, depending on bacterial growth phase (2). An independent from the host regulation of bacterial growth dynamics, involving the quorum sensing, may underlie an orchestrating role of gut microbiota in the specific alternation and duration of the host appetite cycles.

An important task is to understand molecular mechanisms linking the gut bacteria with the host pathways regulating appetite and feeding behavior. One such molecular target has been identified in Enterobacteriaceae by linking these common gut bacteria with the host melanocortin system, critically involved in the regulation of energy balance. Indeed, a bacterial protein homologue of caseinolytic protease B (ClpB) has been identified as a conformational mimetic of a-melanocyte-stimulating hormone (a-MSH), an anorexigenic neuropeptide (3). E.coli ClpB is present in but gut lumen and plasma and is able to activate directly intestinal and central satiety pathways, respectively. From the other hand, autoimmune reaction against ClpB can be involved in the pathophysiology of eating disorders via production of IgG cross-reactive with a-MSH (3-5). Thus, these findings reveal mechanisms linking specific gut bacteria with the host specific molecular pathways regulating appetite in both normal and pathological conditions. Author proposes a new theoretical model of appetite control integrating the energy needs of both the host and gut bacteria (1). These data are actively exploited by TargEDys SA, a start-up company developing probiotic-based therapy for altered feeding behavior and body weight.



  1. Fetissov SO (2017) Role of the gut microbiota in host appetite control: bacterial growth to animal feeding behaviour. Nat Rev Endocrinol 13:11-25.
  2. Breton J, et al. (2016) Gut commensal E.coli proteins activate host satiety pathways following nutrient-induced bacterial growth. Cell Metab 23:1-11.
  3. Tennoune N, et al. (2014) Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide [alpha]-MSH, at the origin of eating disorders. Transl Psychiatry 4:e458.
  4. Fetissov SO, et al. (2002) Autoantibodies against a-MSH, ACTH, and LHRH in anorexia and bulimia nervosa patients. Proc Natl Acad Sci USA 99(26):17155-17160.

5. Fetissov SO, et al. (2005) Autoantibodies against neuropeptides are associated with psychological traits in eating disorders. Proc Natl Acad Sci USA 102(41):14865-14870.