Bifidobacterium longum supplementation improves age‐related delays in fracture repair

Abstract

Age‐related delays in bone repair remains an important clinical issue that can prolong pain and suffering. It is now well established that inflammation increases with aging and that this exacerbated inflammatory response can influence skeletal regeneration. Recently, simple dietary supplementation with beneficial probiotic bacteria has been shown to influence fracture repair in young mice. However, the contribution of the gut microbiota to age‐related impairments in fracture healing remains unknown. Here, we sought to determine whether supplementation with a single beneficial probiotic species, Bifidobacterium longum (B. longum), would promote fracture repair in aged (18‐month‐old) female mice. We found that B. longum supplementation accelerated bony callus formation which improved mechanical properties of the fractured limb. We attribute these pro‐regenerative effects of B. longum to preservation of intestinal barrier, dampened systemic inflammation, and maintenance of the microbiota community structure. Moreover, B. longum attenuated many of the fracture‐induced systemic pathologies. Our study provides evidence that targeting the gut microbiota using simple dietary approaches can improve fracture healing outcomes and minimize systemic pathologies in the context of aging.

Probiotics: Can it modulate fracture healing?

“…They also noted decreased IL-6 levels in the treatment group, in contrast to our observation of an increase in IL-6. In a subsequent study, the same group found similar results in aged mice, although again only probiotic treatment pre-fracture was investigated [ 22 ].…”

The Potential Value of Probiotics after Dental Implant Placement

“…The evidence for the beneficial effects of probiotics initially came from studies on fracture healing and osteoporosis treatment, indicating their systemic effects. Numerous animal and human studies have found that the administration of various probiotic strains, such as Lactobacillaceae and Bifidobacterium species, can accelerate fracture healing, promote osteogenic differentiation, and improve bone trabecular parameters [ 59 , 60 , 61 , 62 ]. It has been suggested in the literature that supplementation with specific strains of Bifidobacterium , particularly in the elderly population, can expedite fracture repair [ 62 ].…”

“…Numerous animal and human studies have found that the administration of various probiotic strains, such as Lactobacillaceae and Bifidobacterium species, can accelerate fracture healing, promote osteogenic differentiation, and improve bone trabecular parameters [ 59 , 60 , 61 , 62 ]. It has been suggested in the literature that supplementation with specific strains of Bifidobacterium , particularly in the elderly population, can expedite fracture repair [ 62 ]. In models of osteoporosis induced by various factors, administration of probiotics such as Lactobacillaceae and Bifidobacterium has been shown to increase bone density, attenuate bone loss, and maintain bone homeostasis [ 56 , 61 , 63 , 64 , 65 , 66 ].…”

“…Immune cells and inflammatory factors greatly influence bone tissue regeneration and stability. Probiotics may regulate systemic and local inflammation levels, thereby promoting bone regeneration and maintaining bone homeostasis [ 30 , 62 ]. The RANKL/RANK pathway, the TNF-α/NF-κB signaling pathway and the Wnt pathway are crucial for regulating osteogenic and osteoclastic activities within bone tissue, and their modulation can be influenced by the inflammatory milieu [ 90 , 91 , 92 , 93 , 94 ].…”

Human breastmilk-derived Bifidobacterium longum subsp. infantis CCFM1269 regulates bone formation by the GH/IGF axis through PI3K/AKT pathway

“…For example, supplementing a single strain of B. longum accelerated the formation of callus, thereby improving the mechanical performance of fractured limbs and promoting bone fracture repair in 18-month-old female mice. 10 B. longum UBBL-64 significantly enhanced bone mass and strength in osteoporotic mice, regulated the ratio of immune cells in lymphocytes, and improved bone microstructure. 11 B. longum 35624® inhibited osteoclast formation through the production of extracellular polysaccharides, thereby activating the TLR2-dependent pathway.…”