{
  "abstract": "Gut microbiota modulate host metabolism, immunity, barrier integrity, and neural function through diverse classes of molecules, including small molecules such as short-chain fatty acids (SCFAs), bile acids, tryptophan metabolites, and microbe-derived peptides and proteins. G protein-coupled receptors (GPCRs) constitute a major receptor system through which the host senses microbiota-derived signals. However, current research has largely focused on ligand recognition, G protein pathways and functional phenotypes, leaving an insufficient understanding of how signals are reorganized after receptor activation to generate functional selectivity. In addition to mediating GPCR desensitization and endocytosis, β-arrestin regulates receptor trafficking, sustains endosomal signaling, and orchestrates signaling scaffold assembly, thereby providing a key mechanistic framework for understanding the spatiotemporal reprogramming of microbiota-derived signaling. This review summarizes both canonical and non-canonical GPCR signaling mechanisms, delineates the roles of β-arrestin in regulating receptor fate, biased signaling, and functional outputs. By integrating the PRESTO-Tango system and the PubMed literature, we analyzed the microbiome-related evidence for the near-complete non-olfactory GPCRome (314 conventional GPCRs) in order to assess the association between distinct classes of microbiota-derived molecules and GPCR-β-arrestin signaling. Current evidence indicates that existing studies are dominated by small-molecule signals, whereas evidence for peptides and proteins remains relatively limited. Moreover, most functional studies cannot be directly interpreted as evidence for β-arrestin-dependent mechanisms. A β-arrestin-centered conceptual framework for GPCR signaling regulation may provide a basis forunderstanding how gut microbiota-associated molecules influence host physiological functions through thespatiotemporal modulation of receptor signaling.",
  "abstract_shown": true,
  "affiliations": [
    "Shandong Key Lab of Complex Medical Intelligence and Aging, The Second School of Clinical Medicine, Research and Translational Center for Immunological Disorders, Shandong Medical and Pharmaceutical University"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yushan Hu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yiru Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Haiyan Yao"
    },
    {
      "affs": [
        0
      ],
      "name": "Siteng Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yice Gao"
    },
    {
      "affs": [
        0
      ],
      "name": "Ruixue Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Hui Sun"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7qjyw1xevxxxd.bib",
  "cited_by": 0,
  "doi": "10.3389/fmicb.2026.1979411",
  "fulltext_url": "https://europepmc.org/articles/PMC13689688",
  "id": "7qjyw1xevxxxd",
  "issns": [
    "1664-302X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fmicb.2026.1979411/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Receptor Mechanisms and Signaling"
    ]
  ],
  "openalex": "W7220959959",
  "pdf_url": "https://europepmc.org/articles/PMC13689688?pdf=render",
  "pmcid": "PMC13689688",
  "pmid": "42923709",
  "published": "2026-10-08",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/7qjyw1xevxxxd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:12Z",
      "native_id": "10.3389/fmicb.2026.1979411",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fmicb.2026.1979411/full"
    },
    {
      "first_seen": "2026-10-30T12:20:33Z",
      "native_id": "MED:42923709",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42923709"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Receptor Mechanisms and Signaling",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Gut microbiota-derived small molecules, peptides, and proteins in GPCR signaling: current evidence for β-arrestin involvement",
  "title_text": "Gut microbiota-derived small molecules, peptides, and proteins in GPCR signaling: current evidence for β-arrestin involvement",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:33Z",
  "url": "https://research.draconitic.com/paper/7qjyw1xevxxxd",
  "venue": "Frontiers in Microbiology",
  "versions": []
}