Gut microbial phenylalanine metabolism contributes to MASLD in a dietary protein-dependent manner
Bah, Y. R.; Nurul Asyiqin Binte Mustafa, D.; Saputri, F. E.; Emoto, T.; Wong, S. H.; Dalan, R.; Wu, W.-K.; Tan, N. S.; Wuestefeld, T.; Kasahara, K.
Show abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects nearly a third of adults worldwide, yet how diet shapes the microbiota's contribution remains unclear. In a diet-induced mouse model varying protein content independently of caloric intake, microbiota depletion ameliorated hepatic steatosis and liver injury under protein- sufficient but not protein-restricted conditions. Caecal and plasma metabolomics implicated microbial phenylalanine catabolism and its host conjugates phenylacetylglutamine (PAGln) and phenylacetylglycine (PAGly). PAGln supplementation exacerbated steatosis and liver injury without altering body weight, adiposity or glucose homeostasis. Individual-antibiotic perturbation with metagenomics linked bacterial phenylalanine catabolic capacity to disease severity, and in gnotobiotic mice, genetic disruption of bacterial phenylalanine-to-phenylacetic acid conversion lowered circulating conjugates and attenuated steatosis and fibrosis. In a human cohort, circulating PAGln was selectively elevated in cardiometabolic MASLD. These findings identify dietary protein availability as a modifier of the contribution of microbial phenylalanine metabolism to MASLD and highlight PAGln as a microbiota-derived metabolite that exacerbates hepatic disease.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Butyrate extends health and lifespan in mice with mitochondrial deficiency 95%
- Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+ Tregs and improve metabolism 95%
- Dietary protein increases T cell independent sIgA production through changes in gut microbiota-derived extracellular vesicles 94%
Similar papers in this journal
- Gut microbes mediate the synergistic effects of dietary cholesterol and saturated fat in driving fibrosing MASH 98%
- Gut Microbiome-derived Propionate Reprograms Alveolar MacrophagesMetabolically and Regulates Lung Injury Responses 94%
- Parity modulates impact of BMI and Gestational Weight Gain on gut microbiota in human pregnancy 93%
Similar papers in this journal
- Gut microbiota-based vaccination engages innate immunity to improve blood glucose control in obese mice 92%
- Lysine tRNA fragments and miR-194-5p co-regulate hepatic steatosis via beta-Klotho and Perilipin 2 92%
- Dietary sulfur amino acid restriction improves glucose homeostasis through hepatic de novo serine synthesis 92%
Similar papers in this journal
- Eicosanoids in the pancreatic tumor microenvironment: a multicellular, multifaceted progression 89%
- Integrated Stress Response and Necroptosis Drive Epithelial Dysfunction in Crohn's Disease: Repurposing Cancer drugs for Permeability Barrier Healing. 89%
- Macrophage Immune-Competent Colon Assembloids for Functional Interrogation of Neuroinflammation-Induced Colonic Dysmotility 88%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.