Doctors often prescribe antibiotics to treat acne in adolescents, but using these medications for a long time can disrupt the balance of bacteria in the gut and lead to changes in the levels of certain chemicals that help build bone mass. Adolescence is a time of significant physical changes due to sex hormones, and acne, a condition that occurs when pores become clogged with oil and dead skin cells, is a common and often distressing experience during this time. In cases where topical treatments are not effective in controlling acne, doctors may turn to systemic antibiotics to help improve symptoms and clear the skin.
Treating acne with systemic antibiotics like minocycline often requires using the medication for an extended period, sometimes as long as two years. However, the long-term effects of using these antibiotics are not fully understood. A study published in the Journal of Clinical Investigation Insight by researchers from the Medical University of South Carolina found a strong connection between the balance of microorganisms in the gut, known as the gut microbiome, and healthy bone development in adolescence. The use of a systemic antibiotic like minocycline for an extended period may have unintended consequences on the critical process of adolescent bone development.
Gut Microbiome Impact on Bone Development
According to Matthew Carson, the first author of the study and a graduate student studying the impact of the gut microbiome on bone development, long-term use of the antibiotic minocycline leads to sustained changes in the gut microbiome that can hinder bone maturation. Chad Novince, DDS, Ph.D., the principal investigator and associate professor in the Department of Oral Health Sciences at the College of Dental Medicine, added that minocycline treatment not only causes changes in the developing skeleton but also disrupts the microbiome in a way that not fully recover after the antibiotic therapy is stopped.
This research builds on previous work from the Novince lab that showed that a high-dose combination of antibiotics triggered an immune response that increased the activity of osteoclasts, cells that break down bone, and impaired bone maturation. This prompted the team to investigate whether there might be clinical situations in which systemic antibiotics could affect bone development during adolescence. They found that minocycline is frequently used as a systemic antibiotic to treat adolescent acne. Minocycline belongs to the tetracycline class of antibiotics, which also includes tetracycline, doxycycline, and sarecycline. These antibiotics work by inhibiting the growth and reproduction of bacteria; in the case of acne, they kill the bacteria that infect pores and reduce the production of certain oils that fuels the growth of pimples and acne.
To see if systemic treatment with minocycline had similar effects on the skeleton as previous antibiotic treatments, Carson and Novince gave mice a clinically relevant dose of minocycline during the pubertal/postpubertal growth period, which is equivalent to adolescence in humans. They found that minocycline therapy did not cause any toxic effects or trigger an immune response, as they had observed previously. However, there were changes in the gut microbiome that resulted in reduced bone mass and impaired skeletal maturation.
Minocycline influences the function of bone forming cells called osteoblasts (shown in yellow and highlighted with arrows).
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Using Acne Antibiotics
These findings highlight an important but often overlooked consequence of using systemic antibiotics for an extended period during adolescence. The researchers also found that long-term minocycline therapy prevented the gut microbiome and skeleton from returning to a stable state even after the therapy was stopped. Previous research suggested that the gut microbiome reaches a mature state in the first few years of life, but more recent studies have indicated that the gut microbiome continues to develop and reach a stable, mature state during adolescence.
Carson explained that it is interesting to note that making changes to the microbiome during adolescence, when it is still developing toward a stable adult state, can have significant effects on the developing skeleton. During puberty, people gain up to 40% of their peak bone mass, which is linked to the maturation of the microbiome. If this process is disrupted and peak bone mass is reduced, it may be harder to maintain bone mass later in life as a result of the natural bone loss that occurs with aging. Therefore, disrupting the microbiome during puberty can have a lasting impact on skeletal health and the risk of fractures.
The Novince team also examined how the microbiome could affect and change the structure of the skeleton. They found that altering the gut microbiome with minocycline disrupted the normal communication between the liver and small intestine, which involves small molecules called bile acids. Normally, bile acids are produced in the liver and transported to the small intestine to aid in digestion and help break down fats. However, their role is now understood to be more complex. Bile acids have not previously been considered important molecules for communication between the gut and the skeleton, according to Novince.
Acne is a skin condition that occurs when the follicles of your hair get plugged with oil and dead skin cells.
The Makeup of Bile Acids
Altering the gut microbiome changes the makeup of bile acids, which can affect host physiology, including bone maturation. The gut microbiome constantly modifies the pool of bile acids in the small intestine, and these bile acids act as messenger molecules that communicate with host cells in the intestine and other parts of the body. For example, bile acids can stimulate bone formation when they interact with osteoblasts. The researchers found that the altered gut microbiome resulting from minocycline treatment produced a different pool of bile acids that failed to activate bone-forming osteoblasts and caused a significant decrease of more than 30% in bone formation and mineralization.
This research demonstrates the benefits of a cross-disciplinary approach to science. To Novince, this research was a true collaboration, which is becoming increasingly important in science. To conduct high-impact research, it is necessary to bring together experts from different fields and disciplines. The team was fortunate to have a strong team, and the work was exciting and enjoyable.
In summary, this study highlights the importance of the communication network between the gut, liver, and bones. It shows that systemic treatment with minocycline has unintended, significant, and long-lasting effects on the skeleton. Carson summarized the findings by saying that treatment of adolescent mice with minocycline caused a change in the gut microbiome and altered bile acid metabolism, which inhibited osteoblast function and impaired skeletal maturation.
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