Gut microbial-derived short-chain fatty acids and bone: a potential role in fracture healing

Abstract

Bone healing complications such as delayed healing or non-union affect 5-10 % of patients with a long-bone fracture and lead to reduced quality of life and increased health-care costs. The gut microbiota and the metabolites they produce, mainly short-chain fatty acids (SCFAs), have been shown to impact nearly all organs of the human body including bone. SCFAs show broad activity in positively influencing bone healing outcomes either by acting directly on cell types involved in fracture healing, such as osteoblasts, osteoclasts, chondrocytes and fibroblasts, or indirectly, by shaping an appropriate anti-inflammatory and immune regulatory response. Due to the ability of SCFAs to influence osteoblast and osteoclast differentiation, SCFAs may also affect the integration of orthopaedic implants in bone. In addition, SCFA-derivatives have already been used in a variety of tissue engineering constructs to reduce inflammation and induce bone tissue production. The present review summarises the current knowledge on the role of the gut microbiota, in particular through the action of SCFAs, in the individual stages of bone healing and provides insights into how SCFAs may be utilised in a manner beneficial for fracture healing and surgical reconstruction.

Taohong Siwu decoction promotes the process of fracture healing by activating the VEGF-FAK signal pathway and systemically regulating the gut microbiota

“…In a novel study, researchers found that Bacteroides and Rikenellaceae may be involved in bone metabolism and fracture risk (Ozaki et al, 2021). In addition, metabolites of gut microbiota, such as short‐chain fatty acids, have been shown to promote fracture healing by reducing inflammation and inducing bone tissue regeneration (Wallimann et al, 2021). Investigators believed that gut microbes affect bone primarily through three mechanisms, namely regulation of nutrient absorption, stimulation of the immune system and translocation of microbes or microbe‐associated molecules across the endothelial barrier (Castaneda et al, 2020; Hernandez, 2017).…”

“Osteomicrobiology”: The Nexus Between Bone and Bugs

“…Butyrate supplementation enhances the production of 5-Hydroxyindole-3-acetic acid (HIAA), an AhR ligand that programs B cells to become Bregs which mitigate inflammatory arthritis ( Rosser et al, 2020 ). Also, SCFAs can positively influence bone healing process by regulating the activity of bone cells and thus can be employed for fracture healing ( Wallimann et al, 2021 ). Collectively, all these studies clearly establish that SCFAs supplementation can be exploited as a potential therapeutics for the management of various bone pathologies including osteoporosis, fractures and RA.…”

Effects of Probiotics and Gut Microbiota on Bone Metabolism in Chickens: A Review

“…The gut microbiota can play an essential role in bone homeostasis by regulating the production of SCFAs and other metabolites ( Figure 2 ) [ 57 , 76 ]. SCFAs are organic fatty acids with two to six carbon atoms, mainly including acetic acid, propionic acid, butyric acid, etc., [ 77 ]. SCFAs are metabolites produced by the interaction between diet and gut microbiota and are considered to be a key link between gut microbiota and bone [ 44 , 77 ].…”

“…SCFAs are organic fatty acids with two to six carbon atoms, mainly including acetic acid, propionic acid, butyric acid, etc., [ 77 ]. SCFAs are metabolites produced by the interaction between diet and gut microbiota and are considered to be a key link between gut microbiota and bone [ 44 , 77 ]. Gut microbiota can promote the intestinal absorption of nutrients by regulating the production of SCFAs.…”