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In Vitro Influence of Specific Bacteroidales Strains on Gut and Liver Health Related to Metabolic
Diego Garcia-Morena1, Maria Victoria Fernandez-Cantos1, Silvia Lopez Escalera2,3
1Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands.
Abstract:
Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a major health risk and a serious worldwide issue. MAFLD typically arises from aberrant lipid metabolism, insulin resistance, oxidative stress, and inflammation. However, subjacent causes are multifactorial. The gut has been proposed as a major factor in health and disease, and over the last decade, bacterial strains with potentially beneficial effects on the host have been identified. In vitro cell models have been commonly used as an early step before in vivo drug assessment and can confer complementary advantages in gut and liver health research. In this study, several selected strains of the order Bacteroidales were used in a three-cell line in vitro analysis (HT-29, Caco-2, and HepG2 cell lines) to investigate their potential as new-generation probiotics and microbiota therapeutics. Antimicrobial activity, a potentially useful trait, was studied, and the results showed that Bacteroidales can be a source of either wide- or narrow-spectrum antimicrobials targeting other closely related strains. Moreover, Bacteroides sp. 4_1_36 induced a significant decrease in gut permeability, as evidenced by the high TEER values in the Caco-2 monolayer assay, as well as a reduction in free fatty acid accumulation and improved fatty acid clearance in a steatosis HepG2 model. These results suggest that Bacteroidales may spearhead the next generation of probiotics to prevent or diminish MAFLD.
Insights
Selected Bacteroidales strains show promise as next-generation probiotics for metabolic dysfunction-associated fatty liver disease (MAFLD). These bacteria reduced gut permeability and improved fatty acid metabolism in vitro, suggesting a new therapeutic avenue for MAFLD.
Area of Science:
- Microbiology
- Gastroenterology
- Metabolic Diseases
Background:
- Metabolic dysfunction-associated fatty liver disease (MAFLD) is a growing global health concern.
- MAFLD pathogenesis involves complex factors including lipid metabolism, insulin resistance, oxidative stress, and inflammation.
- The gut microbiome plays a significant role in host health and disease, with specific bacterial strains showing beneficial effects.
Purpose of the Study:
- To investigate the potential of selected Bacteroidales strains as novel probiotics and microbiota therapeutics.
- To evaluate the antimicrobial properties of Bacteroidales.
- To assess the impact of Bacteroidales on gut barrier function and lipid metabolism in vitro models relevant to MAFLD.
Main Methods:
- In vitro analysis using three cell lines: HT-29, Caco-2, and HepG2.
- Assessment of antimicrobial activity of selected Bacteroidales strains.
- Measurement of gut permeability using Caco-2 monolayer TEER values.
- Evaluation of fatty acid accumulation and clearance in a HepG2 steatosis model.
Main Results:
- Bacteroidales strains demonstrated antimicrobial activity against related bacterial strains.
- Bacteroides sp. 4_1_36 significantly decreased gut permeability in Caco-2 cells.
- This strain also reduced free fatty acid accumulation and enhanced fatty acid clearance in HepG2 cells, indicating a potential anti-steatosis effect.
Conclusions:
- Bacteroidales represent a promising source for developing next-generation probiotics.
- These findings suggest a potential therapeutic strategy for preventing or mitigating MAFLD through gut microbiota modulation.
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