Dietary methionine restriction improves gut microbiota composition and prevents cognitive impairment in<scp>d</scp>-galactose-induced aging mice

Xu, Yao; Yang, Yuhui; Li, Bowen; Xie, Yanli; Shi, Yonghui; Li, Guowei

doi:10.1039/d2fo03366f

Cited by 15 publications

(30 citation statements)

References 87 publications

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“…Previous researches in mice and humans suggested that TMAO production was dependent on variability of the gut microbiota species [ 6 , 47 ]. Of note MR was reported to improve gut microbiota composition in normal, HFD, and aging mice [ 28 , 29 , 40 , 48 ]. Therefore, MR may decrease plasma TMAO levels not by altering the hepatic expression of FMO3 but through decreasing intestinal TMA production via manipulating the gut microbiota composition.…”

Section: Discussionmentioning

confidence: 99%

Dietary Methionine Restriction Alleviates Choline-Induced Tri-Methylamine-N-Oxide (TMAO) Elevation by Manipulating Gut Microbiota in Mice

Yang

et al. 2023

Nutrients

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Dietary methionine restriction (MR) has been shown to decrease plasma trimethylamine-N-oxide (TMAO) levels in high-fat diet mice; however, the specific mechanism used is unknown. We speculated that the underlying mechanism is related with the gut microbiota, and this study aimed to confirm the hypothesis. In this study, we initially carried out an in vitro fermentation experiment and found that MR could reduce the ability of gut microbiota found in the contents of healthy mice and the feces of healthy humans to produce trimethylamine (TMA). Subsequently, mice were fed a normal diet (CON, 0.20% choline + 0.86% methionine), high-choline diet (H-CHO, 1.20% choline + 0.86% methionine), or high-choline + methionine-restricted diet (H-CHO+MR, 1.20% choline + 0.17% methionine) for 3 months. Our results revealed that MR decreased plasma TMA and TMAO levels in H-CHO-diet-fed mice without changing hepatic FMO3 gene expression and enzyme activity, significantly decreased TMA levels and expression of choline TMA-lyase (CutC) and its activator CutD, and decreased CutC activity in the intestine. Moreover, MR significantly decreased the abundance of TMA-producing bacteria, including Escherichia-Shigella (Proteobacteria phylum) and Anaerococcus (Firmicutes phylum), and significantly increased the abundance of short-chain fatty acid (SCFA)-producing bacteria and SCFA levels. Furthermore, both MR and sodium butyrate supplementation significantly inhibited bacterial growth, down-regulated CutC gene expression levels in TMA-producing bacteria, including Escherichia fergusonii ATCC 35469 and Anaerococcus hydrogenalis DSM 7454 and decreased TMA production from bacterial growth under in vitro anaerobic fermentation conditions. In conclusion, dietary MR alleviates choline-induced TMAO elevation by manipulating gut microbiota in mice and may be a promising approach to reducing circulating TMAO levels and TMAO-induced atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Dietary Methionine Restriction Alleviates Choline-Induced Tri-Methylamine-N-Oxide (TMAO) Elevation by Manipulating Gut Microbiota in Mice

Yang

et al. 2023

Nutrients

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“…The gut microbiome plays a crucial role in the intricate relationship between inflammaging, cellular senescence, and aging. Dietary interventions aimed at remodeling the microbiome have the potential to mitigate age-related complications in the gut ( 50 ). Cyclin-dependent kinase inhibitors p16 and p21 serve as valuable markers for cellular senescence, with their levels rising in tandem with the aging process ( 51 ).…”

Section: Discussionmentioning

confidence: 99%

Resistant starches from dietary pulses improve neurocognitive health via gut-microbiome-brain axis in aged mice

Kadyan,

Park,

Hochuli

et al. 2024

Front. Nutr.

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IntroductionCognitive decline is a common consequence of aging. Dietary patterns that lack fibers and are high in saturated fats worsen cognitive impairment by triggering pro-inflammatory pathways and metabolic dysfunctions. Emerging evidence highlights the neurocognitive benefits of fiber-rich diets and the crucial role of gut-microbiome-brain signaling. However, the mechanisms of this diet-microbiome-brain regulation remain largely unclear.MethodsAccordingly, we herein investigated the unexplored neuroprotective mechanisms of dietary pulses-derived resistant starch (RS) in improving aging-associated neurocognitive function in an aged (60-weeks old) murine model carrying a human microbiome.Results and discussionFollowing 20-weeks dietary regimen which included a western-style diet without (control; CTL) or with 5% w/w fortification with RS from pinto beans (PTB), black-eyed-peas (BEP), lentils (LEN), chickpeas (CKP), or inulin fiber (INU), we find that RS, particularly from LEN, ameliorate the cognitive impairments induced by western diet. Mechanistically, RS-mediated improvements in neurocognitive assessments are attributed to positive remodeling of the gut microbiome-metabolome arrays, which include increased short-chain fatty acids and reduced branched-chain amino acids levels. This microbiome-metabolite-brain signaling cascade represses neuroinflammation, cellular senescence, and serum leptin/insulin levels, while enhancing lipid metabolism through improved hepatic function. Altogether, the data demonstrate the prebiotic effects of RS in improving neurocognitive function via modulating the gut-brain axis.

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“…However, the potential role of these microbiota in FGR still needs further investigation. Dietary supplementation of methionine increased the abundance of intestinal Tyzzerella and production of SCFA, alleviating oxidative stress and inflammatory responses in the hippocampus of d-galactose-induced aging mice [ 44 ]. A small randomized controlled trial demonstrated that supplementation with probiotics for two weeks after birth in newborns born at 35 weeks of gestation and who underwent one or more gastrointestinal surgeries resulted in significantly higher relative abundance of nonpathogenic gut bacteria ( Lactobacillaceae ) compared to infants receiving a placebo [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Potential Association of Gut Microbial Metabolism and Circulating mRNA Based on Multiomics Sequencing Analysis in Fetal Growth Restriction

Tang,

Li,

Peng

et al. 2024

Mediators of Inflammation

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Objective. Fetal growth restriction (FGR) is a significant contributor to negative pregnancy and postnatal developmental outcomes. Currently, the exact pathological mechanism of FGR remains unknown. This study aims to utilize multiomics sequencing technology to investigate potential relationships among mRNA, gut microbiota, and metabolism in order to establish a theoretical foundation for diagnosing and understanding the molecular mechanisms underlying FGR. Methods. In this study, 11 healthy pregnant women and nine pregnant women with FGR were divided into Control group and FGR group based on the health status. Umbilical cord blood, maternal serum, feces, and placental tissue samples were collected during delivery. RNA sequencing, 16S rRNA sequencing, and metabolomics methods were applied to analyze changes in umbilical cord blood circulating mRNA, fecal microbiota, and metabolites. RT-qPCR, ELISA, or western blot were used to detect the expression of top 5 differential circulating mRNA in neonatal cord blood, maternal serum, or placental tissue samples. Correlation between differential circulating mRNA, microbiota, and metabolites was analyzed by the Spearman coefficient. Results. The top 5 mRNA genes in FGR were altered with the downregulation of TRIM34, DEFA3, DEFA1B, DEFA1, and QPC, and the upregulation of CHPT1, SMOX, FAM83A, GDF15, and NAPG in newborn umbilical cord blood, maternal serum, and placental tissue. The abundance of Bacteroides, Akkermansia, Eubacterium_coprostanoligenes_group, Phascolarctobacterium, Parasutterella, Odoribacter, Lachnospiraceae_UCG_010, and Dielma were significantly enriched in the FGR group. Metabolites such as aspartic acid, methionine, alanine, L-tryptophan, 3-methyl-2-oxovalerate, and ketoleucine showed notable functional alterations. Spearman correlation analysis indicated that metabolites like methionine and alanine, microbiota (Tyzzerella), and circulating mRNA (TRIM34, SMOX, FAM83A, NAPG) might play a role as mediators in the communication between the gut and circulatory system interaction in FGR. Conclusion. Metabolites (METHIONINE, alanine) as well as microbiota (Tyzzerella) and circulating mRNA (TRIM34, SMOX, FAM83A, NAPG) were possible mediators that communicated the interaction between the gut and circulatory systems in FGR.

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Dietary methionine restriction improves gut microbiota composition and prevents cognitive impairment ind-galactose-induced aging mice

Abstract: Dietary methionine restriction (MR) has been shown to delay aging and ameliorate age-related cognitive impairments. We hypothesized that changes in the gut microbiota may mediate these effects. To test this...

Cited by 15 publications

References 87 publications

Dietary Methionine Restriction Alleviates Choline-Induced Tri-Methylamine-N-Oxide (TMAO) Elevation by Manipulating Gut Microbiota in Mice

Dietary Methionine Restriction Alleviates Choline-Induced Tri-Methylamine-N-Oxide (TMAO) Elevation by Manipulating Gut Microbiota in Mice

Resistant starches from dietary pulses improve neurocognitive health via gut-microbiome-brain axis in aged mice

Potential Association of Gut Microbial Metabolism and Circulating mRNA Based on Multiomics Sequencing Analysis in Fetal Growth Restriction

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