A recent study by Wang et al , published in the World Journal of Psychiatry , provided preventative and therapeutic strategies for the comorbidity of obesity and depression. The gut- brain axis, which acts as a two-way communication system between the gastrointestinal tract and the central nervous system, plays a pivotal role in the pathogenesis of these conditions. Evidence suggests that metabolic byproducts, such as short-chain fatty acids, lipopolysaccharide and bile acids, which are generated by the gut microbiota, along with neurotransmitters and inflammatory mediators within the gut-brain axis, modulate the host's metabolic processes, neuronal regulation, and immune responses through diverse mechanisms. The interaction between obesity and depression via the gut- brain axis involves disruptions in the gut microbiota balance, inflammatory immune responses, and alterations in the neuroendocrine system. Modulating the gut-brain axis, for example, through a ketogenic diet, the use of probiotics, and the supplementation of antioxidants, offers new remedial approaches for obesity and depression. Future research that explores the mechanisms of the gut-brain axis is needed to provide more evidence for clinical treatment.