ABSTRACT
BACKGROUND: Metabolic-dysfunction associated steatotic liver disease (MASLD) is a hepatic manifestation of metabolic syndrome. Studies suggest ornithine aspartate (LOLA) as drug therapy. AIM: To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD. METHODS: Adult male Sprague Dawley rats were randomized into three groups: Control (10 rats fed with a standard diet), MASLD (10 rats fed with a high-fat and choline-deficient diet), and LOLA (10 rats receiving 200 mg/kg/d LOLA, after the 16th week receiving high-fat and choline-deficient diet). After 28 wk of the experiment, animals were euthanized, and feces present in the intestine were collected. Following fecal DNA extraction, the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™ system. RESULTS: Alpha and beta diversity metrics were comparable between MASLD and LOLA. 3 OTUs were differentially abundant between MASLD and LOLA, which belong to the species Helicobacter rodentium, Parabacteroides goldsteinii, and Parabacteroides distasonis. The functional prediction provided two different metabolic profiles between MASLD and LOLA. The 9 pathways differentially abundant in MASLD are related to a change in energy source, adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis. The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate, including tricarboxylic acid cycle pathways, purine/guanosine nucleotides biosynthesis, pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis. CONCLUSION: Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD, it was associated with changes in specific gut microbes and their related metabolic pathways.
ABSTRACT
Mancozeb is a fungicide commonly used in pest control programs, especially to protect vineyards. Its toxicity has already been evidenced in several studies. However, its influence on the composition and diversity of the gut microbiota remains unknown. In this work, the adverse impact of Mancozeb on the intestinal microbiota was investigated using a rodent model. Adult male Sprague Dawley rats were randomized into three groups: Control (standard diet), MZ1 (Mancozeb dose: 250 mg/kg bw/day), and MZ2 (Mancozeb dose: 500 mg/kg bw/day). After 12 weeks of experiment, animals were euthanized, and feces present in the intestine were collected. After fecal DNA extraction, the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™ System. Alpha and beta diversity analysis showed significant differences between Control and Mancozeb groups (MZ1 e MZ2), but no difference between MZ1 and MZ2 was observed. Seven genera significantly increased in abundance following Mancozeb exposure, while five genera decreased. Co-occurrence analyses revealed that the topological properties of the microbial networks, which can be used to infer co-occurrence interaction patterns among microorganisms, were significantly lower in both groups exposed to Mancozeb when compared to Control. In addition, 23 differentially abundant microbial metabolic pathways were identified in Mancozeb-treated groups mainly related to a change in energy metabolism, LPS biosynthesis, and nucleotide biosynthesis. In conclusion, the exposure to Mancozeb presented side effects by changing the composition of the microbiota in rats, increasing bacterial diversity regardless of the dose used, reducing the interaction patterns of the microbial communities, and changing microbial metabolic pathways.
