Western Diet and fecal microbiota transplantation alter phenotypic, liver fatty acids, and gut metagenomics and metabolomics in Mtarc2 knockout mice.

BACKGROUND

The mitochondrial amidoxime-reducing component-2 (Mtarc) enzyme complex is located on the outer mitochondrial membrane and may be involved in lipid metabolism regulation.

AIM

This study evaluated the impact of fecal microbiota transplantation (FMT) on phenotypic outcomes, liver accumulation of fatty acids (FAs), and modifications to the gut microbial community, as well as the abundance of short-chain fatty acids (SCFAs) and amino acids (AAs), in both sexes of Mtarc2 knockout (Mtarc2-KO) and C57BL/6 N mice fed a Western Diet (WD).

METHODOLOGY

Mice were fed a WD (study groups) or normal diet (control groups) and were subjected to intestinal flushing with either a polyethylene glycol (PEG) solution (study groups) or water (control groups); this was followed by intragastrical administration of a human feces suspension (study groups) or water (control groups). Liver FA composition and fecal SCFAs and AAs were measured by mass spectrometry. Metagenomic-based analysis was performed by sequencing the variable V3 and V4 regions of the bacterial 16 S rRNA gene.

PRINCIPAL FINDINGS

Weight gain in C57BL/6 N mice fed a WD was significantly higher than in Mtarc2-KO mice. Compared with water only, intestinal cleansing with PEG resulted in significantly lower weight gain in C57BL/6 N mice but not in Mtarc2-KO mice. FMT did not affect body weight in C57BL/6 N mice, and decreased in Mtarc2-KO females and males fed a ND and a WD, respectively. No significant differences in liver FAs composition were found between mouse strains. While PEG treatment significantly affected liver FAs composition, FMT modulated FAs levels to a much smaller extent. However, neither intestinal cleansing nor FMT affected the microscopic findings of fatty liver. WD feeding affected bacterial diversity, taxonomy and SCFAs and AAs abundances in Mtarc2-KO and C57BL/6 N mice not subjected to PEG treatment. Both intestinal cleansing alone and FMT modulated gut bacterial composition, especially in C57BL/6 N mice, and metabolite abundances in Mtarc2-KO mice.

CONCLUSION

WD and FMT differentially modified phenotypic parameters, liver FA composition, and gut bacteria in comparisons between Mtarc2-KO and C57BL/6 N. This suggests the Mtarc complex plays a significant role in regulating energy metabolism in mice.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1186/s12263-025-00772-x.