Association between behavioural and clinical markers of depression, and the gut microbiota of aflatoxin B1-exposed and chronic unpredictable mild stress-induced rats

Microorganisms play crucial roles in human health, residing not only in the gut but also in the mouth, skin, liver, and stomach. These microbes provide physiological and psychological benefits by producing short-chain fatty acids (SCFAs), secondary metabolites, and nutrients. However, gut microbiota is sensitive to pH, diet, and xenobiotics like aflatoxin B1 (AFB1). Previous research indicated that both AFB1 and chronic unpredictable mild stress (CUMS) influence faecal bacterial counts and cause depressive-like symptoms in animal models. Hence, this present study aimed to investigate further the differences in the relative abundance of gut microbiota across various taxonomic levels (phylum to genus) and their associations between behavioural biomarkers—such as the immobility time (s), sucrose preference (%), and serum brain-derived neurotrophic factor (BDNF) levels (pg/ml) of rats exposed to the low (5μg/kg) and high dose (25μg/kg) of AFB1 and CUMS. In brief, thirty-two Sprague Dawley rats (n=32) were divided into 4 groups (control, low-dose AFB1, high-dose AFB1, CUMS). After the rats were treated for 4 weeks, the behavioural markers i.e immobility time (s) and sucrose preference (%) were assessed using Force Swim Test (FST) and Sucrose Preference Test (SPT), while serum was collected to determine BDNF using ELISA. Besides, their faecal was collected, extracted and analysed further using metagenomic 16s DNA. The results were analysed using MANOVA, and the association between gut microbiota composition and behavioural and clinical markers of depression was determined using Pearson Correlation. The results suggest that Firmicutes and Bacteroidetes are predominant phyla in gut microbiota, with variations in species abundance indicating different responses to AFB1 and CUMS. At the class level, Bacilli (Firmicutes) were more abundant in the low-dose AFB1 group, while Negativicutes (Firmicutes) were more abundant in the CUMS group. At the genus level, high-dose AFB1 decreased Prevotella (Bacteroidota) significantly, and specific taxa like Bacteroides, Anaerovibrio, and Roseburia showed strong correlations with BDNF and immobility time. The study highlights the potential role of specific microbial taxa in neurotrophic factor expression and depressive-like behaviours. These findings underscore the need for further research into the interactions between gut microbiota, BDNF, and depressive disorders to develop targeted antibiotic therapies.

Text 122024 (A).pdf Download (1MB) Official URL or Download Paper: http://ethesis.upm.edu.my/id/eprint/18560

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