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Longevity

Longevity Briefs: Are Gut Microbes The Key To Healthy Bones?

Posted on 16 January 2025

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

As we age, our bones become more susceptible to diseases like osteoporosis, osteoarthritis, and spinal degeneration. These conditions arise due to an imbalance between bone formation by cells called osteoblasts, and bone resorption (breakdown) by their counterpart cells – osteoclasts. Both these cell types are necessary for healthy bone maintenance, but in old age the activity of osteoclasts begins to outstrip that of osteoblasts, leading to a net loss of bone mass. This bone degeneration is a major cause of frailty in old age, as it is related to frequent fractures and disability.

The gut microbiota is a vast community of microorganisms living in our intestines, and it appears to influence many aspects of our health, including bone health. In this review article, researchers give an overview of what we know about how the gut microbiota promotes bone maintenance, as well as how we might harness them to delay or reverse bone ageing.

Overview of the mechanisms of bone ageing.
Microbiota-bone axis in ageing-related bone diseases

The discovery:

Based on their review of existing research, the authors started by highlighting the major known mechanisms explaining how the gut microbiota affects bone metabolism:

  • Gut microbes produce beneficial compounds: The gut microbiota produces beneficial compounds such as short-chain fatty acids (SCFAs). SCFAs are produced when metabolising dietary fibres and can reduce osteoclast production in favour of osteoblasts, while also suppressing inflammation (which plays a role in bone loss). Gut microbes can also boost the production by intestinal cells of beneficial compounds like 5-HT.
  • Nutrient absorption: The gut microbiota enhances the absorption of essential nutrients like calcium, which is necessary for bone formation.
  • Immune system modulation: The gut microbiota has complex interactions with the immune system, and is involved in regulating inflammation and the development of various types of immune cell. Immune cells in turn play an important role in regulating bone metabolism.
  • Hormone regulation: The gut microbiota impacts the secretion of gastrointestinal hormones such as glucagon-like peptide-1 (GLP-1), which stimulates bone formation and suppresses bone resorption. Additionally, around 20% of thyroxine (T4), a hormone produced by the thyroid, is converted into the active form of triiodothyronine (T3) by gut bacteria. Triiodothyronine stimulates the proliferation and differentiation of osteoblasts.
  • The gut-brain axis: One of the more remarkable discoveries about the gut microbiota is that it is able to influence brain activity, which may in turn influence bone formation and resorption.

The implications:

The composition and diversity of the gut microbiota declines with increasing age, which may contribute to bone ageing in humans. Compared to the other fundamental changes that occur during ageing, it seems to be relatively easy to restore the gut microbiota of an older person to a younger state using faecal microbiota transplantation (FMT). Simply transferring gut microbes from the faeces of a young, healthy donor into the gut of the recipient produces lasting beneficial changes to microbiota composition, but the human health benefits of this are understudied. In the meantime, targeting the gut microbiota through probiotics, prebiotics, and dietary interventions could be a more straightforward way (with a better established safety than FMT) to maintain bone health and prevent diseases like osteoporosis and osteoarthritis.


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    References

    Microbiota-bone axis in ageing-related bone diseases https://doi.org/10.3389/fendo.2024.1414350

    Title image by Otto Norin, Upslash

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