Bone fractures severely affect quality of life and mortality in aging populations. Fortunately, research on the impact of gut microbiota (GM) on bone metabolism identifies potential new targets to modify bone mineral density.
Indeed, probiotics may one day be part of effective treatment.
Our skeletons are not inert — far from it. Our bones are constantly being remodeled through complex systems. Bone-forming osteoblasts and bone-resorbing osteoclasts are the major players. Imbalances can lead to osteoporosis, a disease characterized by low bone mass and changes in bone microarchitecture, with an increased risk of fractures.
Fractures can be prevented by reducing the risk of falling, changing lifestyle and nutrition as well as smoking and alcohol abstention. Calcium and vitamin D supplementation are often first-line treatment. In addition, several drugs are available to treat osteoporosis but may present safety and tolerance problems in long-term use. More tools are necessary.
Gut microbiota and bone metabolism
Early evidence of a connection between the gut microbiota and bone metabolism came nearly 20 years ago. Researchers reported that bone mineral density (BMD) was associated with intestinal bacterial overgrowth. Malabsorption of essential elements for bone maintenance processes was thought to be only a part of the complex mechanism of action. Other useful clues came from studies on germ-free mice, which offered observation of gut microbiota regulation in bone mass.
Moreover, explorations of underlying biological mechanisms place the gut microbiota in a complex relationship with bone metabolism.
Gut microbiota may affect bone metabolism by the following mechanisms:
Gut microbiota (depending on composition) may:
- Promote mineral (calcium, magnesium, and phosphate) absorption, crucial to Vitamin D absorption and metabolism.
- Impact pH level of the gut, am important factor for nutrient absorption, especially calcium.
- Have a role in the synthesis of vitamin B and vitamin K as well as the metabolism of bile acids (involved in calcium metabolism.)
- May contribute to the degradation of phytic acid, making phosphate and bound minerals biologically available.
2-Influence on immune system
Evidence for the interaction of gut microbiota and bone cells can be found in immune activity. For example, certain species may lead to an increase in a number of cytokines, including many that are associated with bone metabolism, such as TNF-α. Further, inflammation has been associated with osteoporosis and the intestinal microbiota plays a key role in immune regulation.
3-Influence on gut–brain axis
Impact may also occur via regulation of the synthesis of hormones and neurotransmitters such as serotonin (5-HT). The 5-HT signal transduction system is important for the regulation of bone development and maintenance.
4-Effects by microbial byproducts
Short chain fatty acids (SCFAs) produced by the gut microbiota (e.g. butyrate) play a role in bone formation and mineralization by influencing several signaling pathways. SCFAs may also influence the function of endocrine factors related to bone metabolism, such as peptide YY and glucagon-like peptide 1. In addition, SCFAs improve the solubility of minerals in the colon and may help with their passive absorption.
The overall relationship between the gut microbiota and bone metabolism is summarized in an excellent diagram that appeared in an article titled Association Between Gut Microbiota and Bone Health: Potential Mechanisms and Prospective.
Probiotics effect on bone metabolism
Several genera of bacteria, mainly Lactobacillus and related genera, and Bifidobacterium, have been studied for effect on the regulation of bone mineral density. Go to individual links for details on strains and methods in the several mentioned below.
Studies on animals
- Treating ovariectomized (ovaries have been removed, approximating post-menopausal conditions) mice with Lactobacillus reuteri was shown to significantly decrease osteoclastogenesis and bone resorption, preventing bone loss.
- Other lactobacilli such as Lactobacillus rhamnosus and Lactobacillus paracasei, among others, have shown similar results in mice, according to studies.
- Bifidobacterium longum in ovariectomized rats appeared to partially restrain resulting bone loss.
Studies in humans
- Lactobacillus reuteri in postmenopausal women increased tibial bone density and circulating vitamin D levels.
- High yogurt intake (probiotic starter cultures regulated) led to higher bone mineral density in a 2017 study with mature adults.
- Lactobacillus helveticus fermented milk had a positive acute effect on calcium metabolism in a study with 20 postmenopausal women. Some types of gut bacteria may help break down proteins contained in milk to biologically active peptides; thus the bacteria may regulate the beneficial effects from milk consumption on bone metabolism.
Together with diet, lifestyle and drugs, manipulating gut microbiota using specific probiotics appears to be a potential strategy to prevent and treat osteoporosis. Of course, more clinical studies are needed to identify optimum strains and dosages.
Chen, Yuan-Cheng et al. “Association Between Gut Microbiota and Bone Health: Potential Mechanisms and Prospective.” The Journal of clinical endocrinology and metabolism vol. 102,10 (2017): 3635-3646. doi:10.1210/jc.2017-00513
Locantore, Pietro et al. “The Interplay between Immune System and Microbiota in Osteoporosis.” Mediators of inflammation vol. 2020 3686749. 26 Feb. 2020, doi:10.1155/2020/3686749