Abstract
BackgroundIntestinal bacteria influence bone remodeling in rodents, and antibiotic manipulation of the rodent gut microbiota increases bone formation and prevents ovariectomy-induced bone loss. In theory, these effects may be mediated by changes in sex hormone biotransformation in the gut, gut serotonin secretion or nutrition-induced secretion of glucagon-like peptide 2 (GLP-2) and glucose-dependent insulinotropic hormone (GIP). Antibiotics change the human gut microbiota, but the effect of antibiotic treatment on human bone turnover is unknown.MethodsWe analyzed serum levels of bone turnover markers, serotonin, GLP-2 and sex hormones before, immediately after, and eight, 42 and 180 days after a 4-day per oral antibiotic cocktail (vancomycin 500 mg, gentamycin 40 mg and meropenem 500 mg once-daily) in twelve healthy adult males. Fasting and meal-stimulated procollagen type I amino-terminal propeptide (P1NP), C-telopeptide of type I collagen (CTX) and osteocalcin levels were measured.ResultsWhile the antibiotic course reduced the stool abundance and composition of anaerobic bacteria as confirmed by cultivation studies, neither short nor long-term alterations in serum P1NP, CTX and osteocalcin were observed. Furthermore, we did not observe any changes in levels of serum GLP-2, serotonin or sex hormones.ConclusionEradication of anaerobic bacteria from healthy adult males had no effect on serum bone turnover markers.
Highlights
Intestinal bacteria influence bone remodeling in rodents, and antibiotic manipulation of the rodent gut microbiota increases bone formation and prevents ovariectomy-induced bone loss
Gut bacteria have the potential to influence bone metabolism through at least five different pathways: 1) By modulating secretion of gut-derived serotonin and/or gut hormones, which are involved in postprandial bone turnover [6, 7], 2) by chancing host immune cell activity with subsequent impact on bone cell differentiation and activity [1, 8], 3) by metabolizing and transforming intestinally excreted steroid compounds, including sex hormones [9], 4) by stimulating activity in the somatotropic axis [2, 3], and 5) by influencing intestinal absorption of Mikkelsen et al bone mineral content (BMC) Endocrine Disorders (2018) 18:60 vitamins, calcium or other micronutrients involved in bone homeostasis [10]
Blood samples were taken from 12 healthy, male volunteers subjected to a four-day broad spectrum antibiotics course consisting of once-daily administration of 500 mg meropenem, 500 mg vancomycin and 40 mg gentamicin dissolved in apple juice and ingested orally
Summary
Intestinal bacteria influence bone remodeling in rodents, and antibiotic manipulation of the rodent gut microbiota increases bone formation and prevents ovariectomy-induced bone loss In theory, these effects may be mediated by changes in sex hormone biotransformation in the gut, gut serotonin secretion or nutrition-induced secretion of glucagon-like peptide 2 (GLP-2) and glucose-dependent insulinotropic hormone (GIP). Broad-spectrum antibiotics, by changing the gut microbiota, decreased insulin-like growth factor 1 (IGF-1), increased bone mass and reduced bone resorption in two-month-old BALB/c mice [3] and broad-spectrum antibiotic treatment increased the expression of incretin hormones including glucagon-like peptide 2 (GLP-2) [13], which in turn may influence bone resorption [14], and decrease the inflammatory state in rodents [15]
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