Hure, M. | bioRxiv Science

bioRxiv2024

Gut microbiota regulates food intake in a rodent model of binge-eating disorder

ObjectiveBinge-eating disorder is characterized by recurrent episodes of consumption of large amounts of food within a short period of time, without compensatory behaviours. This disease is a major public health issue since it decreases patients quality of life and is associated with numerous comorbidities, encompassing anxiety, depression and complications associated with obesity. The pathophysiology of binge-eating disorder is complex and involves both endogenous, environmental and sociocultural factors. The gut microbiota has been proposed to be an important player in the onset or maintenance of eating disorders. Here, we aim to better delineate the potential role of the gut microbiota in binge-eating disorder. MethodWe used a model of binge-eating disorder where eight-weeks-old C57Bl/6 female mice had access during 2 hours, every 2 days over a 10-day period, to a highly palatable and high-calorie diet. Half of the animals received antibiotics to deplete their gut microbiota. Eating behaviour and other behavioural parameters were compared between groups. ResultsWe observed an increase in food intake in mouse exposed to high-fat high-sucrose diet, as well as tachyphagia and craving for food during binge-eating episodes. We demonstrate the gut microbiota depletion further increases food intake, specifically during binge-eating episodes. DiscussionThese results show that the gut microbiota is involved in the control of food intake during episodes of binge-eating. This strengthens the potential role of the gut bacteria in binge-eating disorder and open the way for future therapeutic strategies aiming at targeting patients gut microbiota.

animal behavior and cognition↗

bioRxiv2024

Staphylococcus warneri dampens SUMOylation and promotes intestinal inflammation

Gut bacteria play key roles in intestinal physiology, via the secretion of diversified bacterial effectors. Many of these effectors remodel the host proteome, either by altering transcription or by regulating protein post-translational modifications. SUMOylation, a ubiquitin-like post-translational modification playing key roles in intestinal physiology, is a target of gut bacteria. Mutualistic gut bacteria can promote SUMOylation, via the production of short- or branched-chain fatty acids (SCFA/BCFA). In contrast, several pathogenic bacteria were shown to dampen SUMOylation in order to promote infection. Here, we challenge this dichotomic vision by showing that Staphylococcus warneri, a non-pathogenic bacterium of the human gut microbiota, decreases SUMOylation in intestinal cells. We identified that Warnericin RK, a hemolytic toxin secreted by S. warneri, targets key components of the host SUMOylation machinery, leading to the loss of SUMO-conjugated proteins. We further demonstrate that the dampening of SUMOylation triggered by Warnericin RK promotes inflammation, and, more particularly, TNF-dependent intestinal inflammatory responses. Together, these results highlight the diversity of mechanisms used by non-pathogenic bacteria from the gut microbiota to manipulate host SUMOylation. They further highlight that changes in gut microbiota composition may impact intestinal inflammation, by changing the equilibrium between bacterial effectors promoting or dampening SUMOylation.

microbiology↗