Rapid and relaying deleterious effects of a gastrointestinal pathogen, Citrobacter rodentium, on bone, an extra-intestinal organ
Enteropathogenic infections cause pathophysiological changes in the host but their effects beyond the gastrointestinal tract are undefined. Here, using <i>Citrobacter rodentium</i> infection in mouse, which mimics human diarrheal enteropathogenic <i>Escherichia coli</i>, we show that gastrointestinal infection negatively affects bone remodeling, leading to compromised bone architecture. Transmission of infection through fecal-oral route from <i>Citrobacter rodentium</i>-infected to non-infected mice caused bone loss in non-infected cage mates. Mice with B cell deficiency (<i>Igh6</i>-/- mice) failed to clear <i>C. rodentium</i> infection and exhibited more severe and long-term bone loss compared to WT mice. Unbiased cytokine profiling showed an increase in circulating tumor necrosis factor α (TNFα) levels following <i>Citrobacter rodentium</i> infection, and immunoneutralization of TNFα prevented infection-induced bone loss completely in WT and immunocompromised mice. These findings reveal rapid, relaying, and modifiable effects of enteropathogenic infections on an extraintestinal organ-bone, and provide insights into the mechanism(s) through which these infections affect extraintestinal organ homeostasis.
Authors
- X. Sherry Liu (ORCID: https://orcid.org/0000-0001-7247-2232)
- Amrita Mishra (ORCID: https://orcid.org/0000-0002-7509-908X)
- Sujeet Kumar (ORCID: https://orcid.org/0000-0002-8207-4358)
- Amita Sharma (ORCID: https://orcid.org/0000-0001-5854-2767)
- Namrita Halder
- Mohd Aslam Yusuf (ORCID: https://orcid.org/0000-0003-2779-9919)
- Cordelia Brandt
- Edward Guo
- Girdhari Lal (ORCID: https://orcid.org/0000-0002-3799-3603)
- Simon Clare
- SVVS Ravi Mangu
- Vijay K. Yadav
- Kunal Sharan (ORCID: https://orcid.org/0000-0003-2139-2544)
- Ivaylo I. Ivanov (ORCID: https://orcid.org/0000-0001-5337-3386)
- Madeline Edwards (ORCID: https://orcid.org/0000-0003-0134-2806)
- Alka Gupta (ORCID: https://orcid.org/0009-0006-0352-8961)
- Parminder Singh
- Abhilipsa Das
- Gordon Dougan (ORCID: https://orcid.org/0000-0003-0022-965X)
- Umrao R Monani
- Devasena Ponnalagu
Institutions
- Rutgers, The State University of New Jersey (US)
- Central Food Technological Research Institute (IN)
- Integral University (IN)
- University of Washington (US)
- University of Cambridge (GB)
- Wellcome Sanger Institute (GB)
- New India Foundation (IN)
- National Centre for Cell Science (IN)
- Gujarat Kidney Foundation (IN)
- National Institute of Immunology (IN)
- Columbia University (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- iScience
- Published
- 2025-01-16
- DOI
- https://doi.org/10.1016/j.isci.2025.111802
- Citations
- 3
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 2.42
Funders
- Wellcome Trust
- Innovation and Technology Commission
- National Institute of Immunology
- National Institutes of Health
- National Institute on Aging
- Eunice Kennedy Shriver National Institute of Child Health and Human Development