LC-QToF-Based Metabolomics Identifies Aberrant Tissue Metabolites Associated with a Higher-Fat Diet and Their ‘Reversion to Healthy’ with Dietary Probiotic Supplementation

Metabolites · 4 authors, 2 centres

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TL;DR

Using Ossabaw pigs as an obesity model, this nontargeted metabolomic study found that several tissue metabolites aberrantly altered by a higher-fat diet reverted to healthy-diet-associated levels upon probiotic supplementation with Lacticaseibacillus paracasei. The kidney and brain cortex were the most diet-sensitive tissues examined.

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This preclinical study used Ossabaw pigs as a model for obesity to examine how a higher-fat diet and probiotic supplementation with Lacticaseibacillus paracasei affect tissue metabolomes. LC-QToF-based nontargeted metabolomic analysis was performed on select organs across dietary cohorts. The higher-fat diet induced metabolic alterations including impaired liver function, increased bile synthesis and purine degradation, and reduced detoxification, with the kidney and brain cortex appearing most sensitive. Probiotic supplementation altered metabolic flux through the hexosamine biosynthetic pathway, reducing intracellular UDP-GlcNAc levels. Notably, several metabolites aberrantly elevated by the higher-fat diet reverted to healthy-diet-associated levels with probiotic supplementation: S-adenosylhomocysteine and glutathione in the brain cortex, indoxyl sulfate in the kidney, and LysoPE (18:2) in the heart.

STUDY TYPE

other

SPECIALTY

nutrition

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AI pipeline

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ORIGINAL PAPER

PMC10058031

LC-QToF-Based Metabolomics Identifies Aberrant Tissue Metabolites Associated with a Higher-Fat Diet and Their ‘Reversion to Healthy’ with Dietary Probiotic Supplementation

Metabolites

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ABSTRACT

Over 33% of Americans are labeled as obese, leading the World Health Organization to designate obesity as a major public health problem. One consequence of obesity is the development of metabolic syndrome, a condition which has been correlated to an increased risk for developing cardiovascular disease and Type 2 diabetes. Prolonged ingestion of a higher-fat diet, one cause of obesity, results in alterations to the gut microbiome. These alterations are implicated to have a profound role in the evolution and progression of obesity-linked diseases. Probiotics are associated with positive health effects such as limiting pathogen colonization, aiding in digestion, and vitamin synthesis. Using Ossabaw pigs as a model for obesity, and in conjunction with our previous research, we performed an in-depth, nontargeted, metabolomic analysis on select organs to elucidate the effects of dietary supplementation with the probiotic Lacticaseibacillus paracasei . We focused our analysis on the effects of probiotic supplementation on a higher-fat (obesogenic) diet and a nutritionally balanced diet. Notably, our findings reveal that the brain cortex is highly sensitive to dietary influencers, and with probiotic supplementation, several aberrant metabolites associated with a higher-fat diet revert to healthy levels, thus demonstrating the potential for a probiotic intervention for obesity-linked disease.

CITATION EXPORT

Allyson Dailey, Gloria Solano-Aguilar, Joseph F. Urban et al.. LC-QToF-Based Metabolomics Identifies Aberrant Tissue Metabolites Associated with a Higher-Fat Diet and Their ‘Reversion to Healthy’ with Dietary Probiotic Supplementation. Metabolites. (2023). https://doi.org/10.3390/metabo13030358

AUTHORS

4 · 2 CENTRES

Allyson Dailey, Gloria Solano-Aguilar, Joseph F. Urban, Robin D. Couch

1Department of Chemistry and Biochemistry, George Mason University, Manassas, VA 20110, USA
2Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA

EDITOR / REVIEWER

Takayuki Masaki