Background: Maintaining gut microbial homeostasis is crucial for human health, as imbalances in the gut microbiota (GM) can lead to various diseases, including metabolic syndrome (MS), exacerbated by the use of antipsychotic medications such as olanzapine (OLZ). Understanding the role of the GM in OLZ-induced MS could lead to new therapeutic strategies. This study used metagenomic analysis to explore the impact of OLZ on the GM composition and examined how probiotics can mitigate its adverse effects in a rat model. Changes in weight, blood pressure, and lipid levels, which are key parameters defining MS, were assessed. Additionally, this study investigated serotonin, dopamine, and histopathological changes to explore their possible link with the microbiota-gut-brain axis (MGBA). Results: OLZ had an antagonistic effect on serotonin and dopamine receptors, and it was consistently found to alter the composition of the GM, with an increase in the relative abundance (RA) of the Firmicutes/Bacteroidetes phyla ratio and TM7 genera, indicating that the anticommonsal action of OLZ affects appetite and energy expenditure, contributing to obesity, dyslipidemia and increased blood pressure, which are core components of MS. Hepatic steatosis and intestinal damage in OLZ-treated rat tissues further indicate its role in MS. Conversely, the administration of probiotics, either alone or in combination with OLZ, was found to mitigate these OLZ-induced symptoms of MS by altering the GM composition. These alterations included increases in the abundances of the taxa Bacteroidetes, Actinobacteria, Prevotella, Blautia, Bacteroides, Bacteroidales, and Ruminococcaceae and a decrease in Firmicute abundance. These changes helped maintain gut barrier integrity and modulated neurotransmitter levels, suggesting that probiotics can counteract the adverse metabolic effects of OLZ by restoring the GM balance. Moreover, this study highlights the modulation of the MGBA by OLZ as a potential mechanism through which probiotics modulate serotonin and dopamine levels, influencing metabolic health. Conclusion: These findings emphasise the significant impact of OLZ on the GM and its contribution to MS. These findings suggest that interventions targeting the GM, such as probiotics, could mitigate the metabolic side effects of OLZ. Future research should focus on developing integrative treatment approaches that consider the health of the gut microbiome in managing antipsychotic-induced adverse effects.

Purpose: The study aimed to assess the acute toxicity and anti-diabetic activity of Halimedagracilis (green marine alga). Methods: The Halimedagraciliswere collected from the coastal area of the Gulf of Mannar biosphere reserve and shade dried. Methanolic extract of Halimedagracilis (MEHG) was prepared and it was screened for acute toxicity and anti-diabetic activity in the Zebrafish model. In the Acute toxicity study, the Zebrafishes were grouped into 6 groups and dosed with 6.25, 12.5, 25, 50, and 100mg/L of MEHG and observed at 0, 24, 48, 72, and 96 hours’ intervals. Foranti-diabetic activity analysis diabetes was induced using streptozotocin (STZ). The Zebrafish were divided into six groups- control group, positive control, diabetic Zebrafish with three doses of MEHG, and standard control (treated with metformin). Results: Acute toxicity studyshowed no significant behavioral changes and LC50 was determined as 100mg/L. In the diabetic study, test groups when compared to the control group showed: a significant reduction in both fasting and postprandial blood glucose levels and significant changes in the regeneration of pancreatic β-cells, and reduced vacuolization in the islets of Langerhans. Images of the regenerating caudal fins taken at 24, 48 and 72-hours post-amputation displayed significant limb regeneration in MEHG treated fish compared to the control group. Conclusion: These results prove that MEHG in STZ- induced diabetic Zebrafish possess potent anti-diabetic action by ameliorating blood glucose regulation, promoting pancreatic cell regeneration,minimizing long-term diabetic complications bypreventing the emergence of metabolic memory but no behavioral changes.

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