Object: Primary osteoporosis (PO) is the most common bone disease, which is characterized by decreased bone mass, damage of bone tissue microstructure, increased bone fragility and prone to fracture. Gut microbiome may be involved in bone metabolism of PO through gut–brain axis regulation of immune system and endocrine system, however, the specific mechanism is still unclear. The purpose of this study was to characterize the gut microbiome of patients with PO and its possible role in the occurrence and development of the disease. Methods: Fecal samples were collected from 48 PO patients and 48 healthy controls (HC). The composition of gut microbiome community was analyzed by 16s rDNA amplification sequencing, and the difference of gut microbiome composition between PO patients and HC individuals was compared. PICRUSt was also used to predict the biological function of gut microbiome in patients with PO, and to explore its possible role in the occurrence and development of this disease. The classification model is constructed by random forest algorithm so as to screen the key biomarkers. Result:The diversity of gut microorganisms in PO patients was significantly higher than that in HC group (p<0. 05) and there was significant difference in microbial composition in PO group. The abundance of Dialister (0.036 vs. 0.004, p<0.001) and Faecalibacterium (0.331 vs. 0.132, p<0.001) were significantly enriched which were the key flora related to PO. Although no significant correlation between bone mineral density and the richness of microbial communities is found, PICRUST results show that there are a wide range of potential pathways between gut microbiome and PO patients, including genetic information processing, metabolism, environmental information processing, cellular processes, human diseases and organic systems. Notably, the discriminant model based on dominant microflora can effectively distinguish PO from HC (AUC=93.56). Conclusions: The findings show that PO is related to the change of gut microbiome, especially the enriched Dialister and Faecalibacterium genera, which give new clues to understand the disease and provide markers for the diagnosis and new strategies for intervention treatment of the disease.

Osteoarthritis (OA) is a multifactorial joint disease characterized by degeneration of articular cartilage, which leads to joints pain, disability and reduced quality of life in patients with OA. Interpreting the potential mechanisms underlying OA pathogenesis is crucial to the development of new disease modifying treatments. Although multiple factors contribute to the initiation and progression of OA, gut microbiota has gradually been regarded as an important pathogenic factor in the development of OA. Gut microbiota can be regarded as a multifunctional “organ”, closely related to a series of immune, metabolic and neurological functions. This review summarized research evidences supporting the correlation between gut microbiota and OA, and interpreted the potential mechanisms underlying the correlation from four aspects: immune system, metabolism, gut-brain axis and gut microbiota modulation. Future research should focus on whether there are specific gut microbiota composition or even specific pathogens and the corresponding signaling pathways that contribute to the initiation and progression of OA, and validate the potential of targeting gut microbiota for the treatment of patients with OA.

Intestinal flora located within the intestinal tract comprises a large number of cells, which are referred to as the second gene pool of the human body and form a complex symbiotic relationship with the host. The knowledge of the complex interaction between the intestinal flora and various life activities of the host is a novel and rapidly expanding field. Recently, many studies are being conducted on the relationship between the intestinal flora and bone homeostasis and indicate that the intestinal flora can regulate bone homeostasis via the host immune, metabolic, and endocrine systems. What’s more, based on several clinical and preclinical pieces of evidence, changing the composition and function of the host intestinal flora through the application of probiotics, prebiotics, and fecal microbiota transplantation is being considered to be a potential novel target for the regulation of bone homeostasis. Here, we searched relevant literature and reviewed the role of the intestinal flora in the regulation of bone homeostasis and its modulating interventions.

There is a positive causality between coffee consumption and osteoarthritis (OA); however, whether gut microbiota is involved needs to be discussed. Here, we observed that in caffeine consumers, fecal Prevotella copri abundance was positively correlated with subchondral bone mass, serum caffeine concentration was negatively correlated with bone mass, and fecal P. copri was negatively correlated with serum caffeine. In the OA model, caffeine intake aggravated articular cartilage destruction, bone mass loss, and intestinal barrier damage; on the contrary, paraxanthine intake reversed the above lesions. Importantly, after the intestinal P. copri supplement, caffeine-induced lesions in OA mice were effectively alleviated. Mechanically, P. copri has the potential to metabolize caffeine into paraxanthine, and this effect could alleviate the ferroptosis of osteoblast in the OA model. This study screened out that P. copri, an endogenous bacteria, has the ability to metabolize caffeine and revealed its effects on OA progression. IMPORTANCE: There is positive causality between coffee consumption and osteoarthritis (OA). Caffeine exposure is responsible for the reduction of bone mass and restrained osteoblast function. Prevotella copri abundance is exhausted in gut and positively correlated with subchondral bone mass in coffee consumption patients with OA. Supplement of intestinal P. copri alleviates caffeine-induced subchondral bone loss. P. copri has the potential to metabolize caffeine into paraxanthine, and this effect alleviates ferroptosis of osteoblast. Our study illustrated that intestinal P. copri possibly serves as a novel promising treatment for coffee consumers with OA.

ObjectiveRecent studies illustrated that changes of gut microbiome in human body may be related to the pathogenesis of osteoarthritis (OA). We aimed to determine the difference of gut microbiome between patients with osteoarthritis and normal people.MethodsThe samples were collected from 56 patients with osteoarthritis (34 females) and 52 healthy subjects (28 females). High-throughput sequencing of 16S rRNA gene was used to analyze the classification and composition of gut microbiome in OA patients, and then we used Linear discriminant analysis Effect Size (LEfSe) to find out the main differential bacteria and biomarkers in OA patients. At last, PICRUSt was applied to predict the genomic function of gut microbiome in OA patients, and we explored its mechanism in the development of the OA.ResultsThe association between gut microbiome and osteoarthritis has not been demonstrated in detail. Herein, we investigated the gut microbiome of OA patients and its relationship with the disease to evaluate the potential of the gut microbiome in the diagnosis and treatment of osteoarthritis. And we identified that there are significant differences in the β diversity of the gut microbial composition between the control group and OA patients (p＜0.05, respectively), and Bifidobacterium, Faecalibacterium and Alistipes have the potential to become biomarkers of osteoarthritis. Besides, the genomes of gut microbiome in OA patients are enriched in metabolic pathways and lipopolysaccharide biosynthesis (p=0.049, p=0.005), but in signal pathways related to apoptosis, the degree of enrichment was significantly higher than that of healthy people (p=0.006).ConclusionOur research identified that the community composition of gut microbiome in OA patients was different from that in normal groups and explored the role of gut microbiome in the development of osteoarthritis, which may provide a new theoretical basis for the study of osteoarthritis.