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Orthopaedic device implants play a crucial role in restoring functionality to patients suffering from debilitating musculoskeletal diseases or to those who have experienced traumatic injury. However, the surgical implantation of these devices carries a risk of infection, which represents a significant burden for patients and healthcare providers. This review delineates the pathogenesis of orthopaedic implant infections and the challenges that arise due to biofilm formation and the implications for treatment. It focuses on research advancements in the development of next-generation orthopaedic medical devices to mitigate against implant-related infections. Key considerations impacting the development of devices, which must often perform multiple biological and mechanical roles, are delineated. We review technologies designed to exert spatial and temporal control over antimicrobial presentation and the use of antimicrobial surfaces with intrinsic antibacterial activity. A range of measures to control bio-interfacial interactions including approaches that modify implant surface chemistry or topography to reduce the capacity of bacteria to colonise the surface, form biofilms and cause infections at the device interface and surrounding tissues are also reviewed.

Post-embolisation syndrome (PES) is a prevalent complication that occurs in patients following uterine artery embolisation (UAE) for the treatment of uterine fibroids. The aetiology of PES remains incompletely understood, although postulated to result secondary to tissue infarction resulting in release of inflammatory mediators. We followed PRISMA guidelines and performed a systematic review of studies of PES following UAE from inception to October 2022. Our published protocol was prospectively registered. Our search yielded 54 results. We reviewed 22 full texts, and nine articles were included. Observational studies comprised 6/9 relevant studies, with 5/9 retrospective design. The rate of PES was documented in 5/8 studies (excluding case report) with a reported incidence ranging from 4–34.6%. Five of the nine studies studies postulated that the aetiological basis of PES is inflammatory related. Further research is necessary to advance our understanding of PES to define the biological basis of the syndrome with more certainty and gain a consensus on peri-procedure management to reduce incidence and improve patient outcomes.

Melatonin is a pineal indolamine, allegedly known as a circadian rhythm regulator, and an antioxidative and immunomodulatory molecule. In both experimental and clinical trials, melatonin has been shown to have positive effects in various pathologies, as a modulator of important biochemical pathways including inflammation, oxidative stress, cell injury, apoptosis, and energy metabolism. The gut represents one of melatonin’s most abundant extra pineal sources, with a 400-times-higher concentration than the pineal gland. The importance of the gut microbial community—namely, the gut microbiota, in multiple critical functions of the organism— has been extensively studied throughout time, and its imbalance has been associated with a variety of human pathologies. Recent studies highlight a possible gut microbiota-modulating role of melatonin, with possible implications for the treatment of these pathologies. Consequently, melatonin might prove to be a valuable and versatile therapeutic agent, as it is well known to elicit positive functions on the microbiota in many dysbiosis-associated conditions, such as inflammatory bowel disease, chronodisruption-induced dysbiosis, obesity, and neuropsychiatric disorders. This review intends to lay the basis for a deeper comprehension of melatonin, gut microbiota, and host-health subtle interactions.

Sex steroids, derived mainly from gonads, can shape microbiota composition; however, the impact of gonadectomy and sex on steroid production in the gut (i.e., gut steroids), and its interaction with microbiota composition, needs to be clarified. In this study, steroid environment and gut steroidogenesis were analysed by liquid chromatography tandem mass spectrometry and expression analyses. Gut microbiota composition as branched- and short-chain fatty acids were determined by 16S rRNA gene sequence analysis and gas chromatography flame ionisation detection, respectively. Here, we first demonstrated that levels of pregnenolone (PREG), progesterone (PROG), and isoallopregnanolone (ISOALLO) were higher in the female rat colon, whereas the level of testosterone (T) was higher in males. Sexual dimorphism on gut steroidogenesis is also reported after gonadectomy. Sex, and more significantly, gonadectomy, affects microbiota composition. We noted that a number of taxa and inferred metabolic pathways were associated with gut steroids, such as positive associations between Blautia with T, dihydroprogesterone (DHP), and allopregnanolone (ALLO), whereas negative associations were noted between Roseburia and T, ALLO, PREG, ISOALLO, DHP, and PROG. In conclusion, this study highlights the novel sex-specific association between microbiota and gut steroids with possible relevance for the gut-brain axis.

Steroid hormones are essential biomolecules for human physiology as they modulate the endocrine system, nervous function and behaviour. Recent studies have shown that the gut microbiota is directly involved in the production and metabolism of steroid hormones in the periphery. However, the influence of the gut microbiota on levels of steroids acting and present in the brain (i.e., neuroactive steroids) is not fully understood. Therefore, using liquid chromatography–tandem mass spectrometry, we assessed the levels of several neuroactive steroids in various brain areas and the plasma of germ-free (GF) male mice and conventionally colonized controls. The data obtained indicate an increase in allopregnanolone levels associated with a decrease in those of 5α-androstane-3α, 17β-diol (3α-diol) in the plasma of GF mice. Moreover, an increase of dihydroprogesterone and isoallopregnanolone in the hippocampus, cerebellum, and cerebral cortex was also reported. Changes in dihydrotestosterone and 3α-diol levels were also observed in the hippocampus of GF mice. In addition, an increase in dehydroepiandrosterone was associated with a decrease in testosterone levels in the hypothalamus of GF mice. Our findings suggest that the absence of microbes affects the neuroactive steroids in the periphery and the brain, supporting the evidence of a microbiota-mediated modulation of neuroendocrine pathways involved in preserving host brain functioning.

Interactions between the intestinal microbiota, immune system and nervous system are essential for homeostasis in the gut. Inflammasomes contribute to innate immunity and brain–gut interactions, but their role in microbiota–neuro–immune interactions is not clear. Therefore, we investigated the effect of the inflammasome on visceral pain and local and systemic neuroimmune responses after antibiotic-induced changes to the microbiota. Wild-type (WT) and caspase-1/11 deficient (Casp1 KO) mice were orally treated for 2 weeks with an antibiotic cocktail (Abx, Bacitracin A and Neomycin), followed by quantification of representative fecal commensals (by qPCR), cecal short chain fatty acids (by HPLC), pathways implicated in the gut–neuro-immune axis (by RT-qPCR, immunofluorescence staining, and flow cytometry) in addition to capsaicin-induced visceral pain responses. Abx-treatment in WT-mice resulted in an increase in colonic macrophages, central neuro-immune interactions, colonic inflammasome and nociceptive receptor gene expression and a reduction in capsaicin-induced visceral pain. In contrast, these responses were attenuated in Abx-treated Casp1 KO mice. Collectively, the data indicate an important role for the inflammasome pathway in functional and inflammatory gastrointestinal conditions where pain and alterations in microbiota composition are prominent.