The Interplay between Immune System and Microbiota in Osteoporosis

Abstract

Osteoporosis is a disease characterized by low bone mass and alterations of bone microarchitecture, with an increased risk of fractures. It is a multifactorial disorder that is more frequent in postmenopausal women but can be associated to other diseases (inflammatory and metabolic diseases). At present, several options are available to treat osteoporosis trying to block bone reabsorption and reduce the risk of fracture. Anyway, these drugs have safety and tolerance problems in long-term treatment. Recently, gut microbiota has been highlighted to have strong influence on bone metabolism, becoming a potential new target to modify bone mineral density. Such evidences are mainly based on mouse models, showing an involvement in modulating the interaction between the immune system and bone cells. Germ-free mice represent a basic model to understand the interaction between microbiota, immune system, and bone cells, even though data are controversial. Anyway, such models have unequivocally demonstrated a connection between such systems, even if the mechanism is unclear. Gut microbiota is a complex system that influences calcium and vitamin D absorption and modulates gut permeability, hormonal secretion, and immune response. A key role is played by the T helper 17 lymphocytes, TNF, interleukin 17, and RANK ligand system. Other important pathways include NOD1, NOD2, and Toll-like receptor 5. Prebiotics and probiotics are a wide range of substances and germs that can influence and modify microbiota. Several studies demonstrated actions by different prebiotics and probiotics in different animals, differing according to sex, age, and hormonal status. Data on the effects on humans are poor and controversial. Gut microbiota manipulation appears a possible strategy to prevent and treat osteopenia and/or osteoporosis as well as other possible bone alterations, even though further clinical studies are necessary to identify correct procedures in humans.

Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review)

“…The other topic which deserves more attention is HPI-associated dysregulation of gut microbiota [ 239 , 606 , 653 , 654 , 655 , 656 , 657 , 658 , 659 , 660 , 661 , 662 , 663 , 664 , 665 , 666 , 667 ], a phenomenon described also in animal models (infected Mongolian gerbils [ 668 ]) and thought to be due mainly to gut immunopathological/inflammatory responses and suppressed gastric acid secretion following chronic/atrophic gastritis or use of acid-suppressive drugs. Gut dysbiosis by affecting various biological processes contributes to the pathogenesis of OP [ 669 , 670 , 671 , 672 , 673 , 674 , 675 , 676 , 677 , 678 , 679 , 680 , 681 , 682 , 683 , 684 , 685 , 686 , 687 , 688 , 689 , 690 , 691 , 692 , 693 , 694 , 695 , 696 , 697 , 698 , 699 ] as well as to numerous other extra-digestive system diseases associated with OFs [ 700 , 701 , 702 ,…”

“…Restoring a balanced gut microbiota is considered as a therapeutic tool for various diseases, including OP [ 695 , 730 , 731 , 732 , 733 , 734 , 735 , 736 , 737 ]. Recent studies showed that probiotic and prebiotic supplementation increases bone density in healthy individuals, protects against primary and secondary OP [ 687 , 695 , 699 , 734 , 738 , 739 , 740 ] and exerts beneficial effects in many other extra-digestive diseases [ 740 ]. However, despite the established impact of the gut microbiota on host (patho-) physiology, the potential roles of HPI- and medications-induced gut dysbiosis is not mentioned in current guidelines for OP.…”

Influence of HIV Infection and Antiretroviral Therapy on Bone Homeostasis

“…Recently, the gut microbiota has been reported to have an influence on bone metabolism, attracting attention as a prospective new target to balance BMD. The basis of this evidence is mainly concentrated on its involvement in modulating the interface between the immune system and bone cells ( 55 , 56 ).…”

Plant Fortification of the Diet for Anti-Ageing Effects: A Review

“…In comparison to healthy adults, they lack deep sleep and are unable to take sufficient rest as required by the body at this stage [ 20 ]. The bone density decreases and becomes weaker, increasing the risk of fracture [ 21 ]. Due to slow metabolism and hormonal changes, there is a reduction in muscle mass and an increase in body fat [ 22 ].…”