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ORIGINAL RESEARCH article

Front. Nutr.

Sec. Nutrition and Microbes

Volume 12 - 2025 | doi: 10.3389/fnut.2025.1698518

This article is part of the Research TopicModulating the Gut Immune Microenvironment through Nutrients: Molecular Mechanisms and Therapeutic Potential in Immune-Related Gastrointestinal DisordersView all 4 articles

Methionine ameliorates intestinal injury in senescence-accelerated mouse prone-8 (SAMP8) mice by reducing Sulfate-Reducing Bacteria and enhancing barrier function

Provisionally accepted
Ying  WuYing Wu1YONG  ZHANGYONG ZHANG2Min  ZhouMin Zhou2Peng  LiuPeng Liu3Xin  RaoXin Rao2Yong  ZhangYong Zhang4*Tian  Man MiTian Man Mi1*
  • 1The Sixth Medical Center of PLA General Hospital, Army Medical University, Chongqing, China
  • 2Army Medical University, Chongqing, China
  • 3PLA Air Force Medical Center, Beijing, China
  • 4The Fourth Medical Center of PLA General Hospital, Beijing, China

The final, formatted version of the article will be published soon.

Objective: Age-related intestinal barrier dysfunction is a key factor leading to systemic inflammation. Previous studies have found that methionine and its metabolites play a role in anti-aging, but the specific effects on the intestines of aging mice remain unclear. This study aims to explore the effects of different doses of methionine in the diet on intestinal integrity and gut microbiota, and to clarify its potential mechanism in a mouse model of accelerated aging (SAMP8). Method: SAMP8 mice were selected and divided into three groups, each receiving a Methionine-restricted diet (0.17%Met), normal (0.86%Met), or Methionine-supplemented diet (1.64%Met) for four weeks. And SAMP1 mice were used as the control. The intestinal barrier function was evaluated by detecting the levels of LPS, IFABP and Zonulin in serum through ELISA. The integrity of colon tissue, the expression of tight junction proteins (ZO-1 and Occludin) and inflammatory signaling pathways (TLR4/NF-κB) were evaluated by histology, immunofluorescence and Western blot. The composition of the gut microbiota was analyzed by 16S rRNA sequencing, and the levels of hydrogen sulfide (H₂S), sulfomucin in the intestine and the expression of genes related to mucus sulfation were quantitatively detected. Result: Methionine-supplemented die (1.64%Met) significantly improved intestinal aging. Specifically, it is manifested as reducing the expression of cellular senescence markers p16 and p21, lowering the levels of LPS, IFABP and zonulin in serum, restoring the disordered colon structure, and upregulating the expression of tight junction proteins (ZO-1, Occludin). The pro-inflammatory effect of a methionine-supplemented diet on the TLR4/NF-κB pathway reduces the production of H₂S in the intestine.On the contrary, a methionine-restricted diet increased the abundance of norank_f__Desulfovibrionaceae, exacerbating gut microbiota imbalance and barrier dysfunction. Conclusion: A methionine-supplemented diet within the safe range significantly alleviates age-induced intestinal barrier dysfunction by regulating the gut microbiota, inhibiting H₂S-producing bacteria, and restoring the host's intestinal sulfation capacity. A new microbiota-sulfation axis pathway was revealed, which promotes the metabolism of toxic sulfur substances related to the microbiota (such asH2S, indoxyl sulfate, etc.), and methionine supplementation was proposed as a promising nutritional strategy to promote intestinal health and alleviate aging-related pathological changes.

Keywords: Methionine, Intestinal injury, SAMP8 mice, sulfate-reducing bacteria, Barrier function

Received: 03 Sep 2025; Accepted: 02 Oct 2025.

Copyright: © 2025 Wu, ZHANG, Zhou, Liu, Rao, Zhang and Mi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Yong Zhang, zhy-545@163.com
Tian Man Mi, mantian_mi@tmmu.edu.cn

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