A lysine-restricted diet ameliorates obesity via enrichment of Parabacteroides goldsteinii and 1,4-methylimidazoleacetic acid

The effects of dietary amino acid restriction on obesity may be related to the gut microbiome, but its role and mechanism in lysine-restricted diet (LRD) on childhood obesity is largely undefined. Herein, we show that blood lysine levels are elevated in children with obesity compared to healthy controls. Using young mice, we show that LRD ameliorates obesity via gut microbiota modulation. We further identify Parabacteroides goldsteinii (P. goldsteinii) as a candidate contributor and validate that its supplementation reduces obesity phenotype. Metabolomics reveals that P. goldsteinii increases 1,4-methylimidazoleacetic acid (MIAA), a metabolite linked to decreased body weight in animal models. Mechanistically, we show that MIAA inhibits the expression of the demethylase FTO, leading to increased m<sup>6</sup>A modifications on Slc2a4 mRNA via the reader protein YTHDC1. Collectively, these findings suggest a role for P. goldsteinii and its metabolite MIAA on LRD-mediated obesity reduction, potentially via the FTO-SLC2A4 axis to restrict adipose tissue expansion.

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Publication Details

Journal
Nature Communications
Published
2025-11-12
DOI
https://doi.org/10.1038/s41467-025-64892-z
Primary Topic
Gut microbiota and health
Type
article
Field-Weighted Citation Impact
0.00

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article

A lysine-restricted diet ameliorates obesity via enrichment of Parabacteroides goldsteinii and 1,4-methylimidazoleacetic acid

Michael N. Routledge, Zhen Zou, Jian Yao, Jingfu Qiu et al.
Nature Communications
Gut microbiota and health
article

A lysine-restricted diet ameliorates obesity via enrichment of Parabacteroides goldsteinii and 1,4-methylimidazoleacetic acid

Michael N. Routledge, Zhen Zou, Jian Yao, Jingfu Qiu, Chengzhi Chen, Hongyang Zhang, Qin Liu, Jiao Wang, Yuehua Wu, Jun Zhang, Liang Wang, Xuejun Jiang, Zhaoyi Liu, Ahmad Khan, Feng Zhao
article en

Abstract

The effects of dietary amino acid restriction on obesity may be related to the gut microbiome, but its role and mechanism in lysine-restricted diet (LRD) on childhood obesity is largely undefined. Herein, we show that blood lysine levels are elevated in children with obesity compared to healthy controls. Using young mice, we show that LRD ameliorates obesity via gut microbiota modulation. We further identify Parabacteroides goldsteinii (P. goldsteinii) as a candidate contributor and validate that its supplementation reduces obesity phenotype. Metabolomics reveals that P. goldsteinii increases 1,4-methylimidazoleacetic acid (MIAA), a metabolite linked to decreased body weight in animal models. Mechanistically, we show that MIAA inhibits the expression of the demethylase FTO, leading to increased m<sup>6</sup>A modifications on Slc2a4 mRNA via the reader protein YTHDC1. Collectively, these findings suggest a role for P. goldsteinii and its metabolite MIAA on LRD-mediated obesity reduction, potentially via the FTO-SLC2A4 axis to restrict adipose tissue expansion.

Nature CommunicationsVol. 16(1)
University of Leicester (GB), Chongqing Public Health Medical Center (CN), Children's Hospital of Chongqing Medical University (CN), Chongqing Medical University (CN)
National Natural Science Foundation of China, Chongqing Medical University, Centre Scientifique et Technique du Bâtiment
Openalex Percentile: Top 70%
Gut microbiota and health
DOIOpen Access PDFOpenAlex
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