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Microbiota, Inflammation and Bones

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Humans have evolved to interact with a microbial world. The total of micro-organisms (bacteria, fungi, protozoa and, possibly, viruses) that cohabitate an individual is termed its microbiota (1). The term microbiome is sometimes used interchangeably with microbiota, although the strict definition of the latter is reserved for a description of the collective genomes of microorganisms in an individual. Because of advances in technology, especially the ability to sequence the genome of all microorganisms that colonize us, we know much more about the diversity of microorganisms in our microbiota. The largest number of microorganisms in humans is found in the gut and on the skin. Diet, age, genetics and antibiotic use are among the factors that affect the composition of the microbiota (2).


We now know that our immune system has evolved to balance the microbial load in our bodies so that we receive beneficial effects without systemic colonization. Gut flora assist in the metabolism of food and the absorption of vitamins (2). Hence, the control of gut flora is a critical function of the immune system. Complex mechanisms have evolved to regulate the interactions of gut flora and immune cells, which have significant actions on many organ systems including bone. In one animal model it was demonstrated that germ-free mice have a higher bone mass that conventionally housed mice (3) and that housing high bone mass, germ-free mice in conventional housing reverted their bone mass to that of mice that had been conventionally raised.


Why might this occur? The short answer is that we are not yet sure. However, we do have some clues. We know that bone mass is affected by the inflammatory state of an organism. Individuals with inflammatory disease, such as rheumatoid arthritis, have systemic bone loss in addition to periarticular erosions in bone adjacent to inflamed joints (4). In addition, some elements of post-menopausal osteoporosis are regulated by cytokines of immune cell origin like interleukins 1 and tumor necrosis factor (5). What we are now discovering is that the gut microbiota can also influence the inflammatory state of an individual (2). One example of this is the production of regulatory T lymphocytes (Tregs), which function to inhibit inflammation and have additional effect in non-lymphoid tissues (6, 7). Production of Tregs can be influenced by gut microbiota and by diet (8). In addition, in both healthy controls and in individuals with osteoporosis, bone-resorbing activity as measured by serum turnover markers is inversely proportional to the number of circulating Tregs in the blood (9).


These results imply that interactions of the gut microbiota and immune cells also regulate bone mass. Future studies should define more precisely how these interactions are occurring in both health and disease. The hope is that by understanding the interactions of the microbiota, the immune system and bone, we will be able to develop therapies that modulate the responses in disease and enhance bone health.


Joe Lorenzo,

Farmington, CT, USA

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