Explore the vast range of titles available.

The gut microbiota (GM) is the whole of commensal, symbiotic, and pathogenic microorganisms living in our intestine. The GM–host interactions contribute to the maturation of the host immune system, modulating its systemic response. It is well documented that GM can interact with non-enteral cells such as immune cells, dendritic cells, and hepatocytes, producing molecules such as short-chain fatty acids, indole derivatives, polyamines, and secondary bile acid. The receptors for some of these molecules are expressed on immune cells, and modulate the differentiation of T effector and regulatory cells: this is the reason why dysbiosis is correlated with several autoimmune, metabolic, and neurodegenerative diseases. Due to the close interplay between immune and bone cells, GM has a central role in maintaining bone health and influences bone turnover and density. GM can improve bone health also increasing calcium absorption and modulating the production of gut serotonin, a molecule that interacts with bone cells and has been suggested to act as a bone mass regulator. Thus, GM manipulation by consumption of antibiotics, changes in dietary habits, and the use of pre- and probiotics may affect bone health. This review summarizes evidences on the influence of GM on immune system and on bone turnover and density and how GM manipulation may influence bone health.

An expanding body of research asserts that the gut microbiota has a role in bone metabolism and the pathogenesis of osteoporosis. This review considers the human gut microbiota composition and its role in osteoclastogenesis and the bone healing process, specifically in the case of osteoporosis. Although the natural physiologic processes of bone healing and the pathogenesis of osteoporosis and bone disease are now relatively well known, recent literature suggests that a healthy microbiome is tied to bone homeostasis. Nevertheless, the mechanism underlying this connection is still somewhat enigmatic. Based on the literature, a relationship between the microbiome, osteoblasts, osteoclasts, and receptor activator of nuclear factor-kappa-Β ligand (RANKL) is contemplated and explored in this review. Studies have proposed various mechanisms of gut microbiome interaction with osteoclastogenesis and bone health, including micro-RNA, insulin-like growth factor 1, and immune system mediation. However, alterations to the gut microbiome secondary to pharmaceutical and surgical interventions cannot be discounted and are discussed in the context of clinical therapeutic consideration. The literature on probiotics and their mechanisms of action is examined in the context of bone healing. The known and hypothesized interactions of common osteoporosis drugs and the human gut microbiome are examined. Since dysbiosis in the gut microbiota can function as a biomarker of bone metabolic activity, it may also be a pharmacological and nutraceutical (i.e., pre- and probiotics) therapeutic target to promote bone homeostasis.

Increasing interest in functional foods has driven discovery in the area of bioactive compounds. Prebiotics are non-digestible carbohydrate compounds that, when consumed, elicit health benefits and aid in the prevention and treatment of chronic diseases. While prebiotics have been shown to improve a number of chronic, inflammatory conditions, growing evidence exists for prebiotic effects on calcium metabolism and bone health. These novel dietary fibers have been shown to increase calcium absorption in the lower intestines of both preclinical and human models. Rodent models have also been imperative for understanding prebiotic effects on bone mineral density and measures of skeletal strength. Although fewer data are available for humans, bone-related prebiotic effects exist across the lifecycle, suggesting benefits for attainment of peak bone mass during adolescence and minimized bone resorption among postmenopausal women. These effects are thought to occur through prebiotic–microbe interactions in the large intestine. Current prebiotic mechanisms for improved mineral absorption and skeletal health include alterations in gut microbiota composition, production of short-chain fatty acids, altered intestinal pH, biomarker modification, and immune system regulation. While the majority of available data support improved mineral bioavailability, emerging evidence suggests alternate microbial roles and the presence of an intricate gut–bone signaling axis. Overall, the current scientific literature supports prebiotic consumption as a cost-effective and sustainable approach for improved skeletal health and/or fracture prevention. The goal of this review is to discuss both foundational and recent research in the area of prebiotics, mineral metabolism, and bone health.

The mutualistic interaction between the gut microbiota (GM) and its host profoundly shapes many aspects of our physiology. The composition and activity of the gut microbiota is modulated by environmental factors such as dietary habits and antibiotic treatments. In rodents, studies demonstrate that the GM is a crucial regulator of bone metabolism and that modulation of the GM composition by probiotic interventions can prevent castration-induced bone loss. Short-term colonization of germ-free mice with GM results in an activation of CD4+T cells, resulting in increased levels of pro-inflammatory cytokines in bone and thereby activation of osteoclastic bone resorption. Besides these immune-mediated effects on bone mass, the GM is involved in nutritional uptake and may, thereby, regulate overall body growth and bone sizes possibly mediated via altered IGF-I levels. We recently introduced a new term “osteomicrobiology” for the rapidly emerging research field of the role of the microbiota in bone health. This research field is aimed to bridge the gaps between bone physiology, gastroenterology, immunology, and microbiology. Future studies will determine if the GM is a novel therapeutic target for osteoporosis and if the GM composition might be used as a biomarker for fracture prediction.

The repair of infected bone defects is still challenging in the fields of orthopedics, oral implantology and maxillofacial surgery. In these cases, the self-healing capacity of bone tissue can be significantly compromised by the large size of bone defects and the potential/active bacterial activity. Infected bone defects are conventionally treated by a systemic/local administration of antibiotics to control infection and a subsequent implantation of bone grafts, such as autografts and allografts. However, these treatment options are time-consuming and usually yield less optimal efficacy. To approach these problems, novel biomaterials with both antibacterial and osteoinductive properties have been developed. The antibacterial property can be conferred by antibiotics and other novel antibacterial biomaterials, such as silver nanoparticles. Bone morphogenetic proteins are used to functionalize the biomaterials with a potent osteoinductive property. By manipulating the carrying modes and release kinetics, these biomaterials are optimized to maximize their antibacterial and osteoinductive functions with minimized cytotoxicity. The findings, in the past decade, have shown a very promising application potential of the novel biomaterials with the dual functions in treating infected bone defects. In this review, we will summarize the current knowledge of novel biomaterials with both antibacterial and osteoinductive properties.

Three 1,000-year-old mycobacterial genomes from Peruvian human skeletons reveal that a member of the Mycobacterium tuberculosis complex derived from seals caused human disease before contact in the Americas. Tuberculosis in the Americas Mycobacterium tuberculosis has a long history as a human pathogen, but how and when this unfortunate relationship began is not clear. Although the strains found in the Americas today are closely related to those in Europe, archaeological evidence suggests that the disease was present in the New World before contact with Europeans. Johannes Krause and colleagues sequenced three approximately 1,000-year-old M. tuberculosis genomes from human remains in Peru, proving that the pathogen caused human disease in the pre-contact New World. The ancient DNA is most closely related to that found in strains adapted to seals and sea lions. The authors hypothesize that these sea mammals may have contracted the disease from an African host species and carried it across the oceans where exploitation of marine resources by coastal peoples of South America allowed zoonotic transfer. This strain of tuberculosis may have then adapted to humans before being replaced by European strains introduced post-contact. Modern strains of Mycobacterium tuberculosis from the Americas are closely related to those from Europe, supporting the assumption that human tuberculosis was introduced post-contact 1 . This notion, however, is incompatible with archaeological evidence of pre-contact tuberculosis in the New World 2 . Comparative genomics of modern isolates suggests that M. tuberculosis attained its worldwide distribution following human dispersals out of Africa during the Pleistocene epoch 3 , although this has yet to be confirmed with ancient calibration points. Here we present three 1,000-year-old mycobacterial genomes from Peruvian human skeletons, revealing that a member of the M. tuberculosis complex caused human disease before contact. The ancient strains are distinct from known human-adapted forms and are most closely related to those adapted to seals and sea lions. Two independent dating approaches suggest a most recent common ancestor for the M. tuberculosis complex less than 6,000 years ago, which supports a Holocene dispersal of the disease. Our results implicate sea mammals as having played a role in transmitting the disease to humans across the ocean.

Brucellosis is a widespread zoonosis that is acquired by humans from infected animals. Articular complications, particularly brucellar spondylitis, are the most prevalent and disabling manifestations of human brucellosis. Inflammation-mediated osteoclast activation is implicated in -induced bone destruction, but the direct cellular tropism of within bone tissue and the specific effects of infection on osteoclasts remain poorly understood. This study aims to characterize the osteoclast tropism of biovar 3 clinical isolates and their direct regulatory effects on osteoclast-mediated bone destruction in -induced arthritis. clinical isolates were obtained from the bone tissues of human brucellar spondylitis patients in Gansu Province, China. Whole-genome sequencing and biotyping identified their specific biovars. These isolates were used to generate arthritis in immunodeficient NCG mice; bone homeostasis in these mice was assessed via ELISA. We assessed their cellular tropism and osteoclast-modulating effects through intracellular survival assays, immunofluorescence, histopathology, TRAP staining, and resorption pit analysis. Three clinical isolates of biovar 3 were obtained from arthritis lesions in patients from Gansu. Genomic analysis revealed homology with geographically diverse Chinese strains. Although these isolates reached splenic bacterial loads similar to the virulent strain 16M, they did not cause splenomegaly by two weeks post-infection. The isolates displayed strong tropism for human and murine osteoclasts, achieving significantly higher intracellular loads compared to osteoblasts or osteocytes. Infection at the osteoclast precursor/bone marrow macrophage stage enhanced early osteoclastogenesis while inhibiting late-stage apoptosis and fusion, leading to prolonged osteoclast survival and aggravated bone resorption and defects. In contrast, conditioned medium from infected osteoblasts or osteocytes had minimal impact on late-stage osteoclast differentiation. These findings elucidate the mechanisms underlying pathological bone defects in brucellar arthritis. The direct bacterial effects, together with the formation of an osteoclast-derived pro-survival niche, account for the prevalence of brucellar arthritis as the most common complication of chronic brucellosis. Targeting the interaction between and osteoclasts may thus offer a novel therapeutic strategy for preventing and treating -induced osteolytic lesions.

Hundreds of trillions of bacteria are present in the human body in a mutually beneficial symbiotic relationship with the host. A stable dynamic equilibrium exists in healthy individuals between the microbiota, host organism, and environment. Imbalances of the intestinal microbiota contribute to the determinism of various diseases. Recent research suggests that the microbiota is also involved in the regulation of the bone metabolism, and its alteration may induce osteoporosis. Due to modern molecular biotechnology, various mechanisms regulating the relationship between bone and microbiota are emerging. Understanding the role of microbiota imbalances in the development of osteoporosis is essential for the development of potential osteoporosis prevention and treatment strategies through microbiota targeting. A relevant complementary mechanism could be also constituted by the permanent relationships occurring between microbiota and microRNAs (miRNAs). miRNAs are a set of small non-coding RNAs able to regulate gene expression. In this review, we recapitulate the physiological and pathological meanings of the microbiota on osteoporosis onset by governing miRNA production. An improved comprehension of the relations between microbiota and miRNAs could furnish novel markers for the identification and monitoring of osteoporosis, and this appears to be an encouraging method for antagomir-guided tactics as therapeutic agents.

Background. The epidemiology, pathogenesis, clinical manifestations, management, and outcome of Candida osteomyelitis are not well understood. Methods. Cases of Candida osteomyelitis from 1970 through 2011 were reviewed. Underlying conditions, microbiology, mechanisms of infection, clinical manifestations, antifungal therapy, and outcome were studied in 207 evaluable cases. Results. Median age was 30 years (range, ≤1 month to 88 years) with a >2:1 male:female ratio. Most patients (90%) were not neutropenic. Localizing pain, tenderness, and/or edema were present in 90% of patients. Mechanisms of bone infection followed a pattern of hematogenous dissemination (67%), direct inoculation (25%), and contiguous infection (9%). Coinciding with hematogenous infection, most patients had ≥2 infected bones. When analyzed by age, the most common distribution of infected sites for adults was vertebra (odds ratio [OR], 0.09; 95% confidence interval [CI], .04–.25), rib, and sternum; for pediatrie patients (≤18 years) the pattern was femur (OR, 20.6; 95% CI, 8.4–48.1), humerus, then vertebra/ribs. Non-albicans Candida species caused 35% of cases. Bacteria were recovered concomitantly from 12% of cases, underscoring the need for biopsy and/or culture. Candida septic arthritis occurred concomitantly in 21%. Combined surgery and antifungal therapy were used in 48% of cases. The overall complete response rate of Candida osteomyelitis of 32% reflects the difficulty in treating this infection. Relapsed infection, possibly related to inadequate duration of therapy, occurred among 32% who ultimately achieved complete response. Conclusions. Candida osteomyelitis is being reported with increasing frequency. Localizing symptoms are usually present. Vertebrae are the most common sites in adults vs femora in children. Timely diagnosis of Candida osteomyelitis with extended courses of 6–12 months of antifungal therapy, and surgical intervention, when indicated, may improve outcome.

Bacteria play an important role in the degradation of bone material. However, much remains to be learnt about the structure of their communities in degrading bone, and how the depositional environment influences their diversity throughout the exposure period. We genetically profiled the bacterial community in an experimental series of pig bone fragments (femur and humeri) deposited at different well-defined environments in Denmark. The bacterial community in the bone fragments and surrounding depositional environment were studied over one year, and correlated with the bioerosion damage patterns observed microscopically in the bones. We observed that the bacterial communities within the bones were heavily influenced by the local microbial community, and that the general bone microbial diversity increases with time after exposure. We found the presence of several known collagenase producing bacterial groups, and also observed increases in the relative abundance of several of these in bones with tunneling. We anticipate that future analyses using shotgun metagenomics on this and similar datasets will be able to provide insights into mechanisms of microbiome driven bone degradation.