Gut Microbial Metabolites in Inflammatory, Metabolic, and Neurologic Disorders..

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This is an unedited manuscript accepted for publication and provided as an Article in Press for early access at the author’s request. The article will undergo copyediting, typesetting, and galley proof review before final publication. Please be aware that errors may be identified during production that could affect the content. All legal disclaimers of the journal apply.

Year : 2026 | Volume : 3 | 01 | Page :
    By

    Atul Khajuria *1,,

  • Ashish Kumar 2,,

  • Prabhdeep Singh,

  • Mahesh Gaba,,

  1. Dean, Department of Allied & Health Care Sciences, Rayat Bahra Professional University, Hoshiarpur, Chandigarh Rd, VPO, Bohan, Hoshiarpur, Punjab, India
  2. Assistant Professor, University School of Medical Lifesciences, Rayat, Bahra Professional University,Hoshiarpur., punjab, India
  3. Assistant Professor, University School of Medical Lifescience, Rayat, Bahra Professional University, Hoshiarpur, punjab, India
  4. Faculty, department of Medical Laboratory Science, PCTE Group of Institutes, Jhande [Ludhiana], punjab, India

Abstract

The human gut microbiota transforms dietary and hostderived substrates into a diverse array of metabolites—including shortchain fatty acids (SCFAs), hydrogen sulfide (H₂S), bile acid derivatives, indoles, trimethylamine Noxide (TMAO), branchedchain amino acid (BCAA) derivatives, and lipopolysaccharide (LPS)—that act as key signaling mediators along epithelial, immune, endocrine, and neural axes. These metabolites regulate barrier integrity, energy homeostasis, inflammation, and gut–brain
communication and are increasingly implicated in the pathogenesis of inflammatory bowel disease (IBD), obesity, type 2 diabetes, metabolic dysfunction–associated steatotic liver disease (MASLD), and central nervous system (CNS) disorders. SCFAs, particularly butyrate, support colonocyte metabolism, reinforce
tight junctions, promote regulatory T cells, and modulate enteroendocrine hormone release, whereas dysbiosis-associated depletion of SCFA-producing taxa correlates with barrier failure and heightened inflammation in IBD, metabolic disease, and neuroinflammatory conditions. Microbiota-derived H₂S exhibits dose-dependent effects, contributing to mucosal defense at physiological levels but impairing butyrate oxidation, damaging the epithelium, and worsening metabolic control when produced in excess.

Microbial conversion of primary to secondary bile acids shapes FXR/TGR5 signaling, lipid and glucose metabolism, innate immunity, and microbial ecology, while perturbations in bile acid pools are linked to MASLD, insulin resistance, and IBD. In the microbiota–gut–brain axis, SCFAs and tryptophan catabolites influence microglial maturation, neuroinflammation, and neuroplasticity, with reduced SCFA levels and altered indole profiles described in Parkinson’s disease, multiple sclerosis, and mood disorders. Emerging therapeutic strategies target these metabolite pathways using highfiber and prebiotic diets, SCFA- producing probiotics, fecal microbiota transplantation, bile acid receptor modulators, and approaches to modulate H₂S and other metabolites, though current human evidence is largely associative and
heterogeneous. Future work integrating multi-omics with longitudinal and interventional designs, alongside efforts toward standardization and personalization, will be essential to establish causality and safely harness microbial metabolites as precision targets in inflammatory, metabolic, and neurologic disorders.

Keywords: Keywords- Gut Microbiota Metabolites, Short-Chain Fatty Acids (SCFAs), Microbiota–Gut–Brain Axis, Metabolic and Inflammatory Disorders, Bile Acid Signaling.

How to cite this article:
Atul Khajuria *1,, Ashish Kumar 2,, Prabhdeep Singh, Mahesh Gaba,. Gut Microbial Metabolites in Inflammatory, Metabolic, and Neurologic Disorders… Emerging Trends in Metabolites. 2026; 03(01):-.
How to cite this URL:
Atul Khajuria *1,, Ashish Kumar 2,, Prabhdeep Singh, Mahesh Gaba,. Gut Microbial Metabolites in Inflammatory, Metabolic, and Neurologic Disorders… Emerging Trends in Metabolites. 2026; 03(01):-. Available from: https://journals.stmjournals.com/etm/article=2026/view=239641


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Ahead of Print Subscription Review Article
Volume 03
01
Received 21/02/2026
Accepted 14/03/2026
Published 25/03/2026
Publication Time 32 Days
23

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