INTRODUCTION: Trace elements such as manganese (Mn) are essential for various biological processes, including enzyme activation, metabolic pathways, and antioxidant defences. Given its involvement in these critical processes, maintaining adequate Mn levels is crucial for overall health. METHODS: The experimental design involved 24 male Wistar rats divided into three groups (n=8 per group): a control group receiving standard Mn supplementation (65 mg/kg), an Mn-deficient group, and a group supplemented with Mn RESULTS: Body and major organ weights were not significantly affected across groups (p=0.083 to p=0.579). However, significant differences were observed in fat tissue percentage (p=0.016) and lean tissue percentage (p<
0.001). Caecal parameters showed higher ammonia levels (p=0.030) and increased pH (p=0.031) in the nano-Mn group. In turn, total SCFA concentrations were highest in the control group, followed by the Mn-deficient and nano-Mn groups (p<
0.001). Enzymatic activities of caecal bacteria differed significantly between the groups, with reduced activity in the nano-Mn group (p<
0.001). Blood plasma analysis revealed significantly lower insulin (p<
0.001) and neurotransmitter levels, including dopamine and serotonin, in the Mn-deficient and nano-Mn groups compared to controls. DISCUSSION: Our findings suggest that both Mn supplementation and deficiency can lead to physiological and biochemical alterations, affecting fat metabolism, gut health and microbial enzymatic activity or neurotransmitter levels highlighting the critical role of Mn in maintaining metabolic homeostasis or its potential implications for nutritional and pharmaceutical interventions.