Bifidobacterium alleviate metabolic disorders via converting methionine to 5’-methylthioadenosine

ABSTRACT

Dietary patterns and corresponding gut microbiota profiles are associated with various health conditions. A diet rich in polyphenols, primarily plant-based, has been shown to promote the growth of probiotic bacteria in the gastrointestinal tract, subsequently reducing the risk of metabolic disorders in the host. The beneficial effects of these bacteria are largely due to the specific metabolites they produce, such as short-chain fatty acids and membrane proteins. In this study, we employed a metabolomics-guided bioactive metabolite identification platform that included bioactivity testing using in vitro and in vivo assays to discover a bioactive metabolite produced from probiotic bacteria. Through this approach, we identified 5’-methylthioadenosine (MTA) as a probiotic bacterial-derived metabolite with anti-obesity properties. Furthermore, our findings indicate that MTA administration has several regulatory impacts on liver functions, including modulating fatty acid synthesis and glucose metabolism. The present study elucidates the intricate interplay between dietary habits, gut microbiota, and their resultant metabolites.

KEYWORDS:

• Bifidobacterium
• 5’-methylthioadenosine
• LC-MS/MS metabolomics
• probiotic
• prebiotic
• postbiotic
• polyphenols

Acknowledgments

We thank the Ministry of Science and Technology (MOST), Republic of China (ROC), for supporting this study (MOST 106-2113-M-002-013-MY2; MOST 109-2636-M-002-005; MOST 112-2113-M-002-018-MY2). We thank mass spectrometry technical research services of NTU Consortia of Key Technologies and Center for Emerging Materials and Advanced Devices for metabolomics technology supply and data analysis. We thank Biotools Co., Ltd. for microbiota sequencing and analysis. We thank ez-Omics Co., Ltd. for visualization of the RNA-seq data.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

C.C.H. and Q.L. conceived the project, analyzed the data, and wrote the draft manuscript with input from all coauthors. R.A.C. wrote the manuscript as well as analyzed and visualized the data. Q.L. performed SPF C57BL/6Narl mouse experiments, fecal and microbial metabolite extraction, purification, and LC-MS analysis. H.B.Z., W.J.C., and Y.H.H performed gut microbial culture. H.Y.C. evaluated the inhibitory activity of metabolites on lipid accumulation in HepG2 cells. H.L.C. performed the C57BL/6Narl germ-free mouse experiments. L.K.S. performed the isotope tracking experiments, PCR analysis, and biosynthetic pathway analysis. L.H.L. extracted the protein and mRNA of the mouse liver and analyzed the RNA-seq data. S.M.T. visualization of the RNA-seq data. M.S.W., W.K.W., and P.Y.L. performed bacterial genome sequencing, genome assembly, and annotation. H.Y.W. and L.H.L. performed quantitative proteomic analysis.

Data and materials availability

The 16S rRNA gene amplicon sequencing, BCRC12585 genome sequencing, and RNA-seq data used in this study have been deposited in the National Center for Biotechnology Information Sequence Read Archive (SRA) under the BioProject ID PRJNA656418.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2300847

Additional information

Funding

The work was supported by the Ministry of Science and Technology, Taiwan [MOST 109-2636-M-002-005]; Ministry of Science and Technology, Taiwan [MOST 106-2113-M-002-013-MY2].