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©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease
Elisa Carolina Lange, Pabulo Henrique Rampelotto, Larisse Longo, Laura Bainy Rodrigues de Freitas, Carolina Uribe-Cruz, Mario Reis Alvares-da-Silva
Elisa Carolina Lange, Pabulo Henrique Rampelotto, Larisse Longo, Laura Bainy Rodrigues de Freitas, Carolina Uribe-Cruz, Mario Reis Alvares-da-Silva, Experimental Laboratory of Hepatology and Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
Elisa Carolina Lange, Larisse Longo, Carolina Uribe-Cruz, Mario Reis Alvares-da-Silva, Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-007, Brazil
Pabulo Henrique Rampelotto, Bioinformatics and Biostatistics Core Facility, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brazil
Pabulo Henrique Rampelotto, Graduate Program in Biological Sciences: Pharmacology and Therapeutics, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-007, Brazil
Carolina Uribe-Cruz, Facultad de Ciencias de la Salud, Universidad Católica de las Misiones, Posadas, Misiones 3300, Argentina
Mario Reis Alvares-da-Silva, Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, RS, Brazil
Mario Reis Alvares-da-Silva, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) researcher, Brasília 71605-001, Brazil
Co-first authors: Elisa Carolina Lange and Pabulo Henrique Rampelotto.
Author contributions: Lange EC and Rampelotto PH contributed equally to this work; Lange EC, Rampelotto PH and Alvares-da-Silva MR performed the conceptualization, methodology, formal analysis, writing – original draft preparation, and writing – review & editing; Longo L, Freitas LBR, Uribe-Cruz C performed methodology and writing – original draft preparation.
Supported by Financiamento e Incentivo à Pesquisa from Hospital de Clínicas de Porto Alegre (FIPE/HCPA), No. 2020-0037; Coordination for the Improvement of Higher Education Personnel, CAPES/PNPD; and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
Institutional animal care and use committee statement: All experimental procedures were approved by the Ethics Committee for the Use of Animals protocol No. 2020-0037, in accordance with international guidelines for animal welfare and measures were taken to minimize animal pain and discomfort.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: He raw data of high-throughput sequencing is available at the NCBI GenBank Sequence Read Archive (SRA) under accession number PRJNA898069.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Mario Reis Alvares-da-Silva, MD, PhD, Professor, Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Porto Alegre 90035-007, RS, Brazil. mrsilva@hcpa.edu.br
Received: December 11, 2023
Revised: February 2, 2024
Accepted: March 5, 2024
Published online: May 27, 2024
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.
Core Tip: In this nutritional model of metabolic dysfunction-associated steatotic liver disease, ornithine aspartate administration did not exhibit any impact on the alpha and beta diversity of the gut microbiota. Nonetheless, notable distinctions were noted among the cohorts concerning Parabacteroides goldsteinii and Parabacteroides distasonis, both of which pose as promising prospects for advanced probiotics owing to their advantageous implications in mitigating inflammation and addressing obesity. The variances observed in bacterial composition and metabolic profiles were directly associated with the presence of L-aspartate.
