Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Impact of altering gut microbiota metabolism on osteomyelitis severity in obesity-related type 2 diabetes

View ORCID ProfileTina I. Bui, Ann Lindley Gill, Robert A. Mooney, View ORCID ProfileSteven R. Gill
doi: https://doi.org/10.1101/2022.01.13.476282
Tina I. Bui
aDepartment of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Tina I. Bui
Ann Lindley Gill
aDepartment of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert A. Mooney
bDepartment of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
cCenter for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Steven R. Gill
aDepartment of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
cCenter for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Steven R. Gill
  • For correspondence: steven_gill@urmc.rochester.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

ABSTRACT

Staphylococcus aureus is an opportunistic pathogen causing osteomyelitis through hematogenous seeding or contamination of implants and open wounds following orthopedic surgeries. The severity of S. aureus-mediated osteomyelitis is enhanced in obesity-related type 2 diabetes (obesity/T2D) due to chronic inflammation impairing both adaptive and innate immunity. Obesity-induced inflammation is linked to gut dysbiosis, with modification of the gut microbiota by high-fiber diets leading to a reduction in the symptoms and complications of obesity/T2D. However, our understanding of the mechanisms by which modifications of the gut microbiota alter host infection responses is limited. To address this gap, we monitored tibial S. aureus infections in obese/T2D mice treated with the inulin-like fructan fiber, oligofructose. Treatment with oligofructose significantly decreased S. aureus colonization and lowered proinflammatory signaling post-infection in obese/T2D mice, as observed by decreased circulating inflammatory cytokines (TNF-α) and chemokines (IP-10, KC, MIG, MCP-1, and RANTES), indicating partial reduction in inflammation. Oligofructose markedly shifted diversity in the gut microbiota of obese/T2D mice mice, with notable increases in the anti-inflammatory bacterium, Bifidobacterium pseudolongum. Analysis of the cecum and plasma metabolome suggested polyamine production was increased, specifically spermine and spermidine. Oral administration of these polyamines to obese/T2D mice resulted in reduced infection severity similar to oligofructose supplementation, suggesting polyamines can mediate the beneficial effects of fiber on osteomyelitis severity. These results demonstrate the contribution of gut microbiota metabolites to the control of bacterial infections distal to the gut and polyamines as an adjunct therapeutic for osteomyelitis in obesity/T2D.

Importance Individuals with obesity-related type 2 diabetes (obesity/T2D) are at a five times increased risk for invasive Staphylococcus aureus osteomyelitis (bone infection) following orthopedic surgeries. With increasing antibiotic resistance and limited discoveries of novel antibiotics, it is imperative we explore other avenues for therapeutics. In this study, we demonstrated that the dietary fiber oligofructose markedly reduced osteomyelitis severity and hyperinflammation following acute implant-associated osteomyelitis in obese/T2D mice. Reduced infection severity is associated with changes in gut microbiota composition and metabolism as indicated by increased production of natural polyamines in the gut and circulating plasma. This work identifies a novel role for the gut microbiome in mediating control of bacterial infections and polyamines as beneficial metabolites involved in improving the obesity/T2D host response to osteomyelitis. Understanding the impact of polyamines on host immunity and mechanisms behind decreasing susceptibility to severe implant-associated osteomyelitis is crucial to improving treatment strategies for this patient population.

  • List of Abbreviations

    Obesity/T2D
    obesity-related type 2 diabetes
    OF
    oligofructose
    CL
    cellulose
    qPCR
    quantitative polymerase chain reaction
    LC-MS
    liquid chromatography-mass spectrometry
    DI
    direct injection
    CFU
    colony forming unit
    PBS
    phosphate buffered saline
    SCFA
    short-chain fatty acids
    PA
    polyamine
    GTT
    glucose tolerance test
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
    Back to top
    PreviousNext
    Posted January 14, 2022.
    Download PDF
    Email

    Thank you for your interest in spreading the word about bioRxiv.

    NOTE: Your email address is requested solely to identify you as the sender of this article.

    Enter multiple addresses on separate lines or separate them with commas.
    Impact of altering gut microbiota metabolism on osteomyelitis severity in obesity-related type 2 diabetes
    (Your Name) has forwarded a page to you from bioRxiv
    (Your Name) thought you would like to see this page from the bioRxiv website.
    CAPTCHA
    This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
    Share
    Impact of altering gut microbiota metabolism on osteomyelitis severity in obesity-related type 2 diabetes
    Tina I. Bui, Ann Lindley Gill, Robert A. Mooney, Steven R. Gill
    bioRxiv 2022.01.13.476282; doi: https://doi.org/10.1101/2022.01.13.476282
    Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
    Citation Tools
    Impact of altering gut microbiota metabolism on osteomyelitis severity in obesity-related type 2 diabetes
    Tina I. Bui, Ann Lindley Gill, Robert A. Mooney, Steven R. Gill
    bioRxiv 2022.01.13.476282; doi: https://doi.org/10.1101/2022.01.13.476282

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
    • Tweet Widget
    • Facebook Like
    • Google Plus One

    Subject Area

    • Microbiology
    Subject Areas
    All Articles
    • Animal Behavior and Cognition (3479)
    • Biochemistry (7318)
    • Bioengineering (5296)
    • Bioinformatics (20197)
    • Biophysics (9976)
    • Cancer Biology (7703)
    • Cell Biology (11250)
    • Clinical Trials (138)
    • Developmental Biology (6418)
    • Ecology (9916)
    • Epidemiology (2065)
    • Evolutionary Biology (13280)
    • Genetics (9352)
    • Genomics (12554)
    • Immunology (7674)
    • Microbiology (18939)
    • Molecular Biology (7417)
    • Neuroscience (40893)
    • Paleontology (298)
    • Pathology (1226)
    • Pharmacology and Toxicology (2126)
    • Physiology (3140)
    • Plant Biology (6838)
    • Scientific Communication and Education (1270)
    • Synthetic Biology (1891)
    • Systems Biology (5296)
    • Zoology (1085)