{
  "abstract": "Cancer cachexia is a debilitating disease characterized by muscle atrophy. Given the gut dysbiosis in cancer cachexia and the increasing evidence of a gut-muscle axis, we explored the potential beneficial effects of bacteria-dependent metabolites on myotube atrophy. Using both hypothesis-driven and hypothesis-free approaches, in-depth metabolomic analysis of blood samples from cachectic C26 tumor-bearing mice treated or not with antibiotics, as well as disease-free germ-free and conventionalized mice, identified 7 bacteria-dependent metabolites decreased under cachectic conditions. Such alterations were not mediated by reduced caloric intake. Among them, 2 metabolites, namely 2-phenylpropanoic acid (2PPA, also known as 2-phenylpropionic acid) and 3-(3,4-dihydroxyphenyl)propanoic acid (3,4OHPP, also known as 3,4-dihydroxyhydrocinnamic acid or dihydrocaffeic acid), demonstrated anti-atrophying effect, alone and in combination, on mouse C2C12 myotubes. Transcriptomics revealed that these 2 bacteria-dependent metabolites restored the amino acid homeostasis with an activation of ATF4 and the serine biosynthesis pathway. Pharmacological inhibition of the phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme of this pathway, prevented the anti-atrophying effects of 2PPA and 3,4OHPP, indicating a causal role for PHGDH in this effect. By identifying microbiota-dependent metabolites as potential therapeutic levers, the current work not only advances our understanding of microbiome-host crosstalk in disease but also opens avenues for innovative, targeted interventions to mitigate muscle atrophy.",
  "abstract_shown": true,
  "affiliations": [
    "UCLouvain, Louvain Drug Research Institute, LDRI, Metabolism and Nutrition Research Group, MNut, Brussels, Belgium - Walloon Excellence in LifeSciences and BIOt"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "A. L. Degraeve"
    },
    {
      "name": "X. Li"
    },
    {
      "name": "C. Lefevre"
    },
    {
      "name": "E. Piron"
    },
    {
      "name": "A. L. Loriot"
    },
    {
      "name": "N. Delzenne"
    },
    {
      "name": "A. M. Neyrinck"
    },
    {
      "affs": [
        0
      ],
      "name": "L. Bindels"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/eyzyvehxdbnyb.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.17.752337",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752337v1.full",
  "id": "eyzyvehxdbnyb",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752337v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "microbiology"
    ],
    [
      "openalex",
      "1312|Muscle Physiology and Disorders"
    ]
  ],
  "openalex": "W7213623123",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752337v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/eyzyvehxdbnyb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:11Z",
      "native_id": "10.64898/2026.09.17.752337",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752337v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "Gut microbiota-dependent phenylpropanoic acid derivatives reduced in cancer cachexia protect against myotube atrophy",
  "title_text": "Gut microbiota-dependent phenylpropanoic acid derivatives reduced in cancer cachexia protect against myotube atrophy",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:11Z",
  "url": "https://research.draconitic.com/paper/eyzyvehxdbnyb",
  "venue": "bioRxiv",
  "versions": []
}