The influence of the gut microbiota on bone

AO Trauma
K Thompson, F Moriarty

Background

It has become increasingly evident that the gut microbiota plays a crucial role in many diseases, including bone-associated morbidities, such as osteoporosis, and possibly also fracture healing. 

In this project, we are investigating the impact of the gut microbiota on bone in health and during a fracture related infection. 

One way the gut microbiota interacts with bone is through production of metabolites, especially short-chain fatty acids (SCFAs). Butyrate is one class of SCFAs and we found, that butyrate (C4) inhibits murine, as well as human osteoclast formation in vitro. We performed RNA sequencing of osteoclast precursors cells treated with butyrate to identify differentially expressed genes, which may play a role in the butyrate mediated inhibition of osteoclastogenesis (Figure 1). In particular, we are focusing on genes involved in osteoclast formation (Figure 2).

 
Figure 1: Volcano plot displaying differential expressed genes (blue dots) following 24h of butyrate
Figure 2: Heatmap showing differential expressed genes involved in osteoclast formation
  • Publication

    A Wallimann, Ma Hildebrand, D Groeger, B Stanic, CA Akdis, S Zeiter, RG Richards, TF Moriarty, L O'Mahony, K Thompson  (2021) An Exopolysaccharide Produced by Bifidobacterium longum 35624® Inhibits Osteoclast Formation via a TLR2-Dependent Mechanism. Calcif Tissue Int 108: 654-666. https://doi.org/0.1007/s00223-020-00790-4

    A Wallimann, W Magrath, K Thompson, T Moriarty, R G Richards, C A Akdis, L O'Mahony, C J Hernandez (2021) Gut microbial-derived short-chain fatty acids and bone: a potential role in fracture healing. Eur Cell Mater 41: 454-470. https://doi.org/10.22203/eCM.v041a29

    Wallimann A, Hildebrand M, Groeger D, Stanic B, Akdis CA, Zeiter S, Richards RG,  Moriarty TF, O'Mahony L, Thompson K.  An exopolysaccharide produced by Bifidobacterium longum 35624(R) inhibits osteoclast formation via a TLR2-dependent mechanism.  Calcif Tissue Int. 2021;epub Jan 3. https://www.ncbi.nlm.nih.gov/pubmed/33388801 

    Wallimann A, Magrath W, Pugliese B, Stocker N, Westermann P, Heider A, Gehweiler D, Zeiter S, Claesson MJ, Richards RG, Akdis CA, Hernandez CJ, O’Mahony L, Thompson K, Moriarty TF. Butyrate inhibits osteoclast activity in vitro and regulates systemic inflammation and bone healing in a murine osteotomy model compared to antibiotic-treated mice. Mediators Inflamm. 2021;2021:8817421, https://doi.org/10.1155/2021/8817421 

     
  • Presentation

    Wallimann A, Thompson K, Stanic B, Akdis C, O'Mahony L, Moriarty F. "The influence of microbial-derived metabolites on bone health" at SBMS Summer School 16-17 May 2019 Bern and at MIM retreat 29-31 August, Grindelwald, Switzerland. (Oral)

    Wallimann A, Thompson K, Stanic B, Akdis C, O'Mahony L, Moriarty F. "The influence of microbial-derived metabolites on bone health" at WIRM 3-6 April 2019 Davos, Switzerland, eCM conference 26-28 June 2019 Davos, Switzerland, SSM Annual Meeting 3-4 September 2019 Zurich, Switzerland and EAACI Winter School 23-26 January 2020, Chamonix, France.

    Wallimann A, Thompson K, Stanic B, Akdis C, O'Mahony L, Moriarty F. Poster award for an outstanding poster presentation at EAACI Winter School 23-26 January 2020, Chamonix, France.

    Wallimann A, Thompson K, Moriarty TF, Akdis C, O'Mahony L. The influence of short-chain fatty acids on bone health. 2020 GR forscht virtual (oral)

    Wallimann A, Thompson K, Puliese B, Magrath W, Moriarty TF, Akdis CA, O'Mahony L. The influence of short-chain fatty acids on bone health. 2020 WIRM virtual (oral)

     

    Wallimann A, Magrath W, Thompson K, Pugliese B, Akdis CA, Richards RG, Hernandez CJ, O'Mahony L, Moriarty TF. Butyrate and antibiotics affect local and systemic processes relevant for bone healing. 2021 WIRM (poster) 

     

    Wallimann A, Magrath W, Thompson K, Pugliese B, Akdis CA, Richards RG, Hernandez CJ, O'Mahony L, Moriarty TF. Short-chain fatty acids and antibiotics affect local and systemic processes relevant for bone healing. 2021 World Microbe Forum online (poster)

     

    Wallimann A, Magrath W, Thompson K, Pugliese B, Akdis CA, Richards RG, Hernandez CJ, O'Mahony L, Moriarty TF. Short-chain fatty acids and antibiotics affect local and systemic processes relevant for bone healing. 2021 Gut-Bone Axis Meeting virtual (oral)

     

    Wallimann A, Magrath W, Thompson K, Pugliese B, Akdis CA, Richards RG, Hernandez CJ, O'Mahony L, Moriarty TF. Impact of Rifampicin levofloxacin on gut microbiome and Short-Chain Fatty Acid production in mice with bone fracture: consequences for bone health. 2021 ECCMID online (poster)

     

     

  • Partner

    Liam O'Mahony, University College Cork, Ireland

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