**1. Introduction**

With the growing obesity epidemic and its associated comorbidities including cardiovascular diseases, diabetes, musculoskeletal disorders, cancer [1], depression [2, 3], and now even Covid-19 [4, 5], there is an urgent need to address this public health issue. As highlighted by the World Health Organization (WHO), obesity is preventable.

The understanding of the physiopathology of obesity started to shift back in 2006 when a publication in Nature highlighted that the microbiota of obese individuals differed from that of lean individuals. In addition, when this microbiota was transplanted into mice, propensity to gain weight was transmitted as well [6].

Since the discovery of the roles of the microbiota in metabolism, Pr. Sergueï Fetissov, neuroendocrinologist and professor of physiology, investigated extensively the roles of the gut microbiota in host appetite control. As early as 2002, he identified human autoantibodies reacting with the key hormone of satiety alpha-melanocyte stimulating hormone (alpha-MSH). He discovered an anorexigenic peptide produced by the microbiota with a homology of sequence with alpha-MSH [7]. In a review published in *Nature Reviews Endocrinology*, he demonstrated that metabolites produced by the microbiota can regulate food intake, and more specifically identified a bacterial protein called caseinolytic peptidase B (ClpB), a conformational antigen mimetic of alpha-MSH (**Figure 1**) [8, 9].

Observations showed that ClpB levels in human fecal or serum samples negatively associated with Body Mass Index (BMI) [10]. Pr. Sergueï Fetissov and Pr. Pierre Déchelotte, gastroenterologist, professor in human nutrition and director of the Gut Brain Axis Laboratory at the French National Institute of Health and Medical Research (Inserm), carried on their investigations to better understand and describe the cause-and-effect relationship, demonstrate the proof of concept on animal models and translate the discovery into a lever of action in the battle against obesity.
