2. Academic Validation
  3. A gut-adipose-nerve axis mediates inulin protection against Western diet-induced somatosensory dysfunction

A gut-adipose-nerve axis mediates inulin protection against Western diet-induced somatosensory dysfunction

  • Brain Behav Immun. 2026 May 4:137:106795. doi: 10.1016/j.bbi.2026.106795.
Chaitanya K Gavini 1,  Laetitia Raux 1,  Gwenaël Labouèbe 1,  Emily Gornick 2,  Sarah Mc Hugh 3,  Nadia Elshareif 1,  Nigel A Calcutt 4,  Pietro G Di Summa 5,  François Gorostidi 6,  Pascale Vonaesch 3,  Virginie Mansuy-Aubert 7
Affiliations

Affiliations

  • 1 Department of Biomedical Sciences, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Vaud 1005, Switzerland.
  • 2 Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
  • 3 Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Vaud 1015, Switzerland.
  • 4 Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA.
  • 5 Department of Plastic and Hand Surgery, University Hospital of Lausanne, University of Lausanne, Lausanne 1005, Switzerland.
  • 6 Department of Otorhinolaryngology-Head and Neck Surgery, Lausanne University Hospital, University of Lausanne, Lausanne, Vaud 1005, Switzerland.
  • 7 Department of Biomedical Sciences, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Vaud 1005, Switzerland. Electronic address: [email protected].
PMID: 42092466 DOI: 10.1016/j.bbi.2026.106795
Abstract

Westernized diets (WDs)-high in fat and sugar and low in fiber-produce somatosensory deficits, chronic pain, and neuropathy, yet the mechanisms linking diet to peripheral nervous system (PNS) pathology remain incompletely defined. Emerging evidence implicates gut-derived metabolites in sensory homeostasis; for example, fecal microbiota transplantation (FMT) from lean donors to WD fed mice reduces hypersensitivity and attenuates PNS inflammation potentially via modifying short chain fatty acid (SCFA) levels, although FMT outcomes are variable. We therefore tested whether targeted modulation of the gut microbiota with fermentable complex carbohydrates (inulin) producing SCFA could reproducibly improve somatosensory function in WD-fed mice. Using an integrated pipeline-behavioral and physiological assays, peripheral nerve electrophysiology, and molecular and immune profiling-we show that inulin improved thermal and mechanical sensory function indirectly by improving metabolic health and remodeling immune cells in adipose tissue depots. Interestingly, in separate genetic experiments we found that deletion of the SCFA receptor FFAR2 (GPR43) in myeloid cells altered thermal sensitivity and adipose inflammatory gene expression, indicating that immune SCFA sensing can modulate pain-related behavior. These findings identify mechanisms by which dietary fiber indirectly preserves PNS function through effects on adiposity and systemic inflammation and provide a tractable alternative to FMT for mitigating WD-associated sensory neuropathy.

Keywords

Dietary fiber; Gut microbiome; Inulin; Metabolism; Microbiome; Microbiome-Gut-adipose-PNS axis; Neuroinflammation; Peripheral nerve function.

Figures
Products