Abstract
Osteoporosis (OP) is a chronic disease in the elderly, and China is entering an aging demographic trend. In recent years, increasing evidence has demonstrated that probiotics can treat osteoporosis. This study aimed to explore the relevant mechanisms and to validate the beneficial effect on osteoporosis by high-throughput metagenome-wide gene sequencing in humans. In this study, compared with controls, several species had altered abundances, and specific functional pathways were found in the OP group. At the species level, the species that had increased in OP individuals were positively correlated to bone resorption markers and negatively correlated to 25-OH-D3 and bone formation markers, with Streptococcus sanguinis showing the strongest relevance, followed by Streptococcus gordonii, Actinomyces odontolyticus, and Olsenella unclassified. Additionally, Actinomyces graevenitzii, enriched in the OP group, was positively correlated to inflammation indicators that included white blood cell (WBC), neutrophil count (NEC), and the neutrophil-to-lymphocyte ratio (NLR) (p < 0.05). Conversely, the levels of Akkermansia muciniphila, Bacteroides eggerthii, Bacteroides fragilis, Bacteroides uniformis, and Butyricimonas synergistic were increased in the control group, which had a negative correlation with bone resorption markers and positive correlation with bone formation markers and 25-OH-D3. Additionally, Bacteroides fragilis had a negative correlation with inflammation indicators (WBC, NEC, and NLR) and the above pathways (p < 0.05). Functional prediction revealed that 106 metabolic pathways, enriched in the OP group, were significantly higher than in the control group (p < 0.05). In particular, pathways related to LPS biosynthesis, phytate degradation, lactate acid, and ethanol fermentation were more abundant in the OP group than in the control and were positively related to WBC and NEC. Taken together, several species with altered abundances and specific functional pathways were found in OP individuals. The role of phytases in OP provides novel epidemiological evidence to elucidate the underlying microbiota-relevant mechanisms in bone mineralization and should be explored further.
Highlights
With changes in living conditions and an increased elderly population, osteoporosis has become a common chronic disease
Compared with the control group, there were no significant differences in sex, age, or biochemical parameters of metabolic syndrome in the OP group of the training dataset, which indicated that the influence of intestinal microbes caused by a common reason, chronic diseases, or nutritional factors could be excluded
Actinomyces graevenitzii, Actinomyces sodontolyticus, Olsenella unclassified, Pantoea unclassified, Streptococcus gordonii, Streptococcus mitis oralis pneumoniae, Streptococcus parasanguinis, and Streptococcus sanguinis were enriched in the OP group, and Akkermansia muciniphila, Bacteroides eggerthii, Bacteroides fragilis, Bacteroides uniformis, and Butyricimonas synergistic were enriched in the control group, which had a negative correlation with inflammatory parameters with Bacteroides eggerthii, showing the strongest positive correlation with BMD
Summary
With changes in living conditions and an increased elderly population, osteoporosis has become a common chronic disease. In elderly patients, osteoporosis fractures cause substantial morbidity and mortality (Hofbauer and Rachner, 2015). In China, it is estimated that the prevalence of osteoporosis is approximately 13%, and the elderly demographic trend may incur an annual cost due to osteoporotic fractures from $27.48 billion in 2020 to $581.97 billion in 2050 (Si et al, 2015). Osteoporosis and osteoporotic fractures affect quality of life and cause a huge economic burden on families and society. To prevent and treat osteoporosis in addition to improving lifestyle (Sun exposure, strengthening exercise, and nutritional supplements), the main measure is drug treatment. Early prediction and new treatment methods for osteoporosis must be urgently identified to minimize the effect of fractures
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