Longitudinal profiling of the microbiome at four body sites reveals core stability and individualized dynamics during health and disease.

To understand the dynamic interplay between the human microbiome and host during health and disease, we analyzed the microbial composition, temporal dynamics, and associations with host multi-omics, immune, and clinical markers of microbiomes from four body sites in 86 participants over 6 years. We found that microbiome stability and individuality are body-site specific and heavily influenced by the host. The stool and oral microbiome are more stable than the skin and nasal microbiomes, possibly due to their interaction with the host and environment. We identify individual-specific and commonly shared bacterial taxa, with individualized taxa showing greater stability. Interestingly, microbiome dynamics correlate across body sites, suggesting systemic dynamics influenced by host-microbial-environment interactions. Notably, insulin-resistant individuals show altered microbial stability and associations among microbiome, molecular markers, and clinical features, suggesting their disrupted interaction in metabolic disease. Our study offers comprehensive views of multi-site microbial dynamics and their relationship with host health and disease.

Improved DNA Extraction and Amplification Strategy for 16S rRNA Gene Amplicon-Based Microbiome Studies.

Next-generation sequencing technology has driven the rapid advancement of human microbiome studies by enabling community-level sequence profiling of microbiomes. Although all microbiome sequencing methods depend on recovering the DNA from a sample as a first critical step, lysis methods can be a major determinant of microbiome profile bias. Gentle enzyme-based DNA preparation methods preserve DNA quality but can bias the results by failing to open difficult-to-lyse bacteria. Mechanical methods like bead beating can also bias DNA recovery because the mechanical energy required to break tougher cell walls may shear the DNA of the more easily lysed microbes, and shearing can vary depending on the time and intensity of beating, influencing reproducibility. We introduce a non-mechanical, non-enzymatic, novel rapid microbial DNA extraction procedure suitable for 16S rRNA gene-based microbiome profiling applications that eliminates bead beating. The simultaneous application of alkaline, heat, and detergent ('Rapid' protocol) to milligram quantity samples provided consistent representation across the population of difficult and easily lysed bacteria equal to or better than existing protocols, producing sufficient high-quality DNA for full-length 16S rRNA gene PCR. The novel 'Rapid' method was evaluated using mock bacterial communities containing both difficult and easily lysed bacteria. Human fecal sample testing compared the novel Rapid method with a standard Human Microbiome Project (HMP) protocol for samples from lung cancer patients and controls. DNA recovered from both methods was analyzed using 16S rRNA gene sequencing of the V1V3 and V4 regions on the Illumina platform and the V1V9 region on the PacBio platform. Our findings indicate that the 'Rapid' protocol consistently yielded higher levels of Firmicutes species, which reflected the profile of the bacterial community structure more accurately, which was confirmed by mock community evaluation. The novel 'Rapid' DNA lysis protocol reduces population bias common to bead beating and enzymatic lysis methods, presenting opportunities for improved microbial community profiling, combined with the reduction in sample input to 10 milligrams or less, and it enables rapid transfer and simultaneous lysis of 96 samples in a standard plate format. This results in a 20-fold reduction in sample handling time and an overall 2-fold time advantage when compared to widely used commercial methods. We conclude that the novel 'Rapid' DNA extraction protocol offers a reliable alternative for preparing fecal specimens for 16S rRNA gene amplicon sequencing.

Longitudinal profiling of the microbiome at four body sites reveals core stability and individualized dynamics during health and disease.

To understand dynamic interplay between the human microbiome and host during health and disease, we analyzed the microbial composition, temporal dynamics, and associations with host multi-omics, immune and clinical markers of microbiomes from four body sites in 86 participants over six years. We found that microbiome stability and individuality are body-site-specific and heavily influenced by the host. The stool and oral microbiome were more stable than the skin and nasal microbiomes, possibly due to their interaction with the host and environment. Also, we identified individual-specific and commonly shared bacterial taxa, with individualized taxa showing greater stability. Interestingly, microbiome dynamics correlated across body sites, suggesting systemic coordination influenced by host-microbial-environment interactions. Notably, insulin-resistant individuals showed altered microbial stability and associations between microbiome, molecular markers, and clinical features, suggesting their disrupted interaction in metabolic disease. Our study offers comprehensive views of multi-site microbial dynamics and their relationship with host health and disease. Study Highlights: The stability of the human microbiome varies among individuals and body sites.Highly individualized microbial genera are more stable over time.At each of the four body sites, systematic interactions between the environment, the host and bacteria can be detected.Individuals with insulin resistance have lower microbiome stability, a more diversified skin microbiome, and significantly altered host-microbiome interactions.

Changes to physical activity behavior during the COVID-19 pandemic and their associated factors: a cross sectional survey of Mexican women.

BACKGROUND: On March 24, 2020, the Mexican Government established social distancing measures to address the outbreak of the COVID-19 pandemic. The resulting home confinement affected daily lifestyle habits such as eating, sleeping, and physical activity (PA). The objectives of this study were to determine changes in PA behaviors among Mexican women due to the COVID-19 pandemic and to assess potential factors associated with these changes. METHODS: This was a cross-sectional study based on an anonymous online questionnaire developed by the Task Force on Physical Activity for Persons with Disabilities (PAPD) within the International Society of Physical and Rehabilitation Medicine (ISPRM). Descriptive, quantitative statistics were used for data analysis. A Chi-squared (χ²) test was used to explore associations between dependent and independent variables. RESULTS: A total of 1882 surveys were completed. Among the respondents, 53.3% declared that their PA was reduced during the pandemic, 26.6% reported similar PA behavior, and 20.1% declared that their PA had increased during the pandemic. Lower PA behavior during the pandemic was associated with lower education levels, stricter pandemic constraints, obesity, and lower self-perceived functioning levels. A statistically significant association between poorer self-perceived mental health and decreased PA behaviors was also found. Respondents who were younger, self-perceived as unimpaired, not overweight, and whose income was not impacted by COVID-19 were associated with higher levels of reported physical and mental health. CONCLUSIONS: The study results identify disparities experienced in PA behavior during the COVID-19 pandemic among Mexican women and highlights the need for social support for PA participation.

Impact of the COVID-19 Pandemic on the Perceived Physical and Mental Health and Healthy Lifestyle Behaviors of People With Disabilities: A Quantitative Analysis of the International Community Survey.

OBJECTIVE: This study aims to determine the perceived impact of the coronavirus pandemic on physical and mental health and healthy lifestyle behaviors in community-dwelling persons with disabilities, as compared with those without disabilities. DESIGN: A prospective cross-sectional study was conducted with a web-based global survey. RESULTS: Over 3 mos, 3550 responses were collected from 65 countries. The study included 2689 responses without skipped questions as full data for analysis. Most respondents were women (82.82%), and approximately half (52.81%) were between the ages of 25 and 39 yrs, followed by those between the ages of 40 and 60 yrs (38.6%). Among the participants, 52% indicated physical activity levels decreased and 20% reported eating less fruit and vegetables than before. Furthermore, 45% noted that they slept less than before. Perceived physical and mental health and changes to eating habits during the pandemic showed a significant difference in people with and without disabilities. Furthermore, perceived effects on physical health had a significant effect on the reported degree of disability. CONCLUSIONS: This study indicates that the pandemic had a larger impact on perceived physical and mental health and changes in eating habits and tobacco use among people with disabilities than people without disabilities.

Changes in Trunk Muscle Activity during Unilateral Weight Bearing and Abnormal Postural Gait in Healthy Individuals.

Background and Objectives: Many people tend to carry their bags or baggage on only one side of their body. Due to smartphone use, people also tend to walk bent forward in a kyphotic posture. In this study, we aimed to assess trunk muscle activity changes due to weight-bearing, carried in the left or right hand, and using three different gait postures. Materials and Methods: We recruited 27 healthy participants (aged 19−75 years) with no history of LBP within the last 6 months before study participation. Electromyographic activities of the lower back and the abdominal muscles of the participants were evaluated using four-channel surface electromyography (EMG). Surface EMG recordings were obtained from four trunk muscles, including the flexor (rectus abdominis (RA), external oblique (EO)) and extensor muscles (lumbar erector spinae (LE), and the superficial lumbar multifidus (LM)), during unilateral weight-bearing tasks and with different gait postures (normal gait, with a sway back, and thoracic kyphosis). Results: In the "unilateral weight-bearing task", there was a significant difference in the activity of all the trunk muscles between the weight-bearing limb side and the opposite side (p < 0.05). The activation of the left trunk muscle was greater than that of the right trunk muscle when the dumbbell was lifted using the right hand. The other side showed the same result. In the "gait posture task" performed by the participants using a sway-back posture, the RA and EO had a higher level of activity in the stance and swing phases compared with that in a neutral gait (p < 0.05). Moreover, in the participants with a thoracic kyphosis posture, the LE and LM had a higher level of activity compared with that in a neutral gait (p < 0.05). Conclusions: Our results indicate that abnormal gait posture and unilateral weight-bearing tasks may impair the balance of trunk muscles, increasing the incidence of LBP. However, further large-scale, prospective, controlled studies are warranted to corroborate our results.

The Impact of the COVID-19 Pandemic on Healthy Lifestyle Behaviors and Perceived Mental and Physical Health of People Living with Non-Communicable Diseases: An International Cross-Sectional Survey.

The huge burden and vulnerability imposed by non-communicable diseases (NCDs) during the COVID-19 pandemic highlighted how healthy lifestyle behaviors and the well-being of people living with NCDs need to be prioritized. The aim of our study is to better understand the impact of the COVID-19 pandemic on healthy lifestyle behaviors and perceived mental and physical health among adults living with NCDs, as compared to people without NCDs. We conducted a cross-sectional study using a global online survey through Qualtrics. Over four months, 3550 participants from 65 countries worldwide responded to the survey. The study included 3079 surveys with no missing data (complete survey responses) that were used for analysis. People with NCDs were more likely to report statistically significant worsening physical health (p = 0.001) and statistically insignificant worsening mental health (p = 0.354) when compared to pre-pandemic levels. They reported lower rates of smoking during the pandemic than those without NCDs, and a statistically significant (p < 0.001) relationship was found between weight gain and NCDs. Therefore, the perceived physical and mental health, including changes in body weight and tobacco consumption, of people with NCDs were significantly impacted during the pandemic. In conclusion, this study indicates that the pandemic had a significant impact on perceived physical and mental health, changes in body weight, and tobacco consumption among people with NCDs.

Examining the Efficacy of Antimicrobial Therapy in Preventing the Development of Postinfectious Glomerulonephritis: A Systematic Review and Meta-Analysis.

Postinfectious glomerulonephritis (PIGN) is an immune-mediated acute glomerulonephritis classically seen weeks after infection with Streptococcus pyogenes, although other infectious etiologies have emerged. While it has become increasingly rare in industrialized regions, it continues to affect children in developing countries. There has been debate as to why incidence rates are declining, including the possibility of improved initial treatment of bacterial infections. The ability of antimicrobial therapy in preventing PIGN as infectious sequelae, however, has not been comprehensively assessed. As varying evidence from published studies exists, the objective of this meta-analysis is to determine if antimicrobial therapy utilized to treat an initial infection has an effect in reducing the development of PIGN in humans. EMBASE, MEDLINE, and CENTRAL were searched using a comprehensive terminology strategy. From an initial search that returned 337 publications, 9 articles were included for analysis. Eight studies showed an incidence of PIGN after antimicrobial use ranging from 0.05% to 10% with a mean standardized difference (MSD) of 0.03 (0.01-0.06). Three studies showed an occurrence of PIGN without antibiotic use ranging from 1% to 13% with an MSD of 0.06 (-0.09-0.21). Our findings suggest that antimicrobial treatment for the initial infection may help diminish the development of PIGN. Although Streptococcus pyogenes infections are generally treated aggressively to prevent rheumatic fever, these findings may help further support the early treatment of bacterial infections to prevent postinfectious sequelae, especially as we consider other infectious etiologies of PIGN antimicrobial resistance.

Factors Influencing the Progression and Direction of Scoliosis in Children with Neurological Disorders.

(1) Background: scoliosis is highly prevalent in children with neurological disorders, however, studies predicting the progression and affecting the direction of scoliosis have been insufficient. We investigated the factors associated with the progression and direction of scoliosis in children with neurological disorders. (2) Method: retrospectively, 518 whole spine radiographs from 116 patients were used for analysis. Factors affecting the progression of scoliosis over time were analyzed using linear mixed-effects model. Factors associated with the apex direction of the scoliosis were analyzed. (3) Results: pelvic obliquity (PO) ≥ 2.5°, gross motor function classification system level V, vertebral rotation, and female sex significantly affect the progression of scoliosis (p = 0.04, <0.001, <0.001, 0.005, respectively). The higher side of PO and the apex side of scoliosis were interrelated (χ² = 14.58, p < 0.001), but the asymmetrical neurological upper extremity involvement was not. (4) Conclusions: severely impaired gross motor function, PO, vertebral rotation, and female sex were significantly related to the progression of scoliosis. The higher side of PO was opposite to the apex side of scoliosis. By identifying the factors that influence the progression of scoliosis, patients at high risk could be more actively intervened to minimize the severe complications.

Access denied: the shortage of digitized fitness resources for people with disabilities.

PURPOSE: The COVID-19 pandemic has drastically impacted every aspect of life, including how people exercise and access fitness resources. Prior to COVID-19, the global burden of disease attributable to sedentary behavior disproportionately affected the health of people with disabilities (PWD). This pre-existing gap has only widened during COVID-19 due to limited disability-friendly digital exercise resources. The purpose of this work is to examine this gap in accessibility to digital fitness resources, and re-frame the notion of accessibility to suit the contemporary context. MATERIALS AND METHODS: Using machine learning, video titles/descriptions about home exercise ordered by relevance populated on YouTube between 1 January 2020 and 30 June 2020 were examined. RESULTS: Using the search terms, "home exercise," "home-based exercise," "exercise no equipment," "workout no equipment," "exercise at home," or "at-home exercise," 700 videos ordered by relevance included 28 (4%) that were inclusive of participants with disabilities. Unfortunately, most digital fitness resources are therefore inaccessible to PWD. The global pause the pandemic has induced may be the right moment to construct a comprehensive, indexed digital library of home-based fitness video content for the disabled. There is a further need for more nuanced understandings of accessibility as technological advancements continue.Implications for RehabilitationPhysical activity is incredibly important to the quality of life and health of all people.Physical activity levels, however, remain lower among persons with disabilities.Access to disability-friendly resources remains a challenge and worsened by the circumstances of COVID-19 due to an apparent lack of digital fitness resources for persons with disabilities.A broader and comprehensive definition of accessibility must recognize digital advances and access to physical activity for persons with disabilities must feature digital resources.

Human macrophage polarization in the response to Mycobacterium leprae genomic DNA.

Infection with Mycobacterium leprae, the causative organism of leprosy, is still endemic in numerous parts of the world including the southwestern United States. The broad variation of symptoms in the leprosy disease spectrum range from the milder tuberculoid leprosy (paucibacillary) to the more severe and disfiguring lepromatous leprosy (multibacillary). The established thinking in the health community is that host response, rather than M. leprae strain variation, is the reason for the range of disease severity. More recent discoveries suggest that macrophage polarization also plays a significant role in the spectrum of leprosy disease but to what degree it contributes is not fully established. In this study, we aimed to analyze if different strains of M. leprae elicit different transcription responses in human macrophages, and to examine the role of macrophage polarization in these responses. Genomic DNA from three different strains of M. leprae DNA (Strains NHDP, Br4923, and Thai-53) were used to stimulate human macrophages under three polarization conditions (M1, M1-activated, and M2). Transcriptome analysis revealed a large number of differentially expressed (DE) genes upon stimulation with DNA from M. leprae strain Thai-53 compared to strains NHDP and Br4923, independent of the macrophage polarization condition. We also found that macrophage polarization affects the responses to M. leprae DNA, with up-regulation of numerous interferon stimulated genes. These findings provide a deeper understanding of the role of macrophage polarization in the recognition of M. leprae DNA, with the potential to improve leprosy treatment strategies.

The Impact of Experiential Learning in Host-Pathogen Research on Medical Students' Interests and Attitudes towards Microbiology and Immunology.

There is a shortage of residents in the infectious diseases (IDs) specialty due to a lack of interest in this field. If the choice of an ID subspecialty is linked to medical school experiences, then how we teach microbiology and immunology could be a factor in the declining interest in the field. We sought to determine whether experiential learning activities on host-pathogen research might improve students' interests and attitudes toward medical microbiology and immunology. Experiential learning of medical students undertaking research project on microbiology/immunology leads to subjective attitude changes (i.e., increased science motivation, confidence, and knowledge) and the development of a new social niche. It also lets students learn new scientific techniques and use novel technological devices, which have an impact in the experiential learning of basic sciences such as microbiology and immunology. The results of this study support the idea of a beneficial effect of experiential learning, which may rekindle interest of medical students in the field of infectious diseases.

Does Motor Tract Integrity at 1 Month Predict Gait and Balance Outcomes at 6 Months in Stroke Patients?

Recovery of balance and gait ability is important in stroke patients. Several studies have examined the role of white matter tracts in the recovery of gait and balance, but the results have been inconclusive. Therefore, we examined whether the integrity of the corticospinal tract (CST), corticoreticular pathway (CRP), and cortico-ponto-cerebellar tract (CPCT) at 1 month predicted balance and gait function 6 months after stroke onset. This retrospective longitudinal observational clinical study assessed 27 patients with first-ever unilateral supratentorial stroke. The subjects underwent diffusion tensor imaging 1 month after the stroke, and the Functional Ambulation Categories (FAC) and Berg Balance Scale (BBS) scores were assessed after 6 months. The normalized fiber number (FN) and fractional anisotropy (FA) results for the CST, CRP and CPCT were also obtained. The FN and FA results for the CST, CRP, or CPCT at 1 month were not related to the gait or balance at 6 months. There was also no difference in FAC values at 1 month after stoke onset among three groups differing in degree of independence of ambulation. The integrity of the CST, CRP, and CPCT on 1 month after stroke onset was not associated with gait or balance after 6 months. The white matter integrity did not predict the clinical outcome.

Could DOAC Be a Better Choice Than Warfarin in Low Compliance Patients with Fontan Procedure?

Background and Objectives: After the Fontan procedure, thromboembolic events need to be prevented. We present a young patient with a history of Fontan procedure and poor adherence to warfarin who developed systemic thromboembolism. He was changed to maintenance dabigatran, which is one of the available direct oral anticoagulants (DOACs). Case presentation: A 20-year-old man was diagnosed with cerebral infarct, pulmonary thromboembolism (PTE), and renal infarcts. He was prescribed warfarin to prevent thromboembolic events after the Fontan procedure. Based on his poor adherence to warfarin, we decided to change the anticoagulant therapy from warfarin to dabigatran 150 mg bid. One month later, his pulmonary thromboembolism regressed. Conclusion: Our case report showed a young adult with low compliance to warfarin who developed cerebral, pulmonary, and renal thromboembolic events. Thus, in our opinion, the change from warfarin to a DOAC was necessary for further prevention and treatment of PTE. A change from warfarin to a DOAC should be considered in patients with poor compliance who are at high risk of thromboembolic events, for example, after the Fontan procedure.

The Long-Term Functional Effect of Thrombectomy on Patients with Middle Cerebral Artery Occlusion Who Exhibit Moderate to Severe Disability.

Background and Objectives: Endovascular thrombectomy (EVT is an emerging gold standard treatment for acute cerebral infarction and may allow functional improvement after subacute cerebral infarction. However, the long-term functional benefits of EVT in patients with moderate to severe disability remain unclear. We investigated the effects of EVT on the activities of daily living (ADL), handicap, gait, and eating in patients with middle cerebral artery (MCA) occlusion who exhibited moderate to severe disability (score of 3-5 on the modified Rankin scale (mRS)) due to stroke, up to six months after onset. Materials and Methods: This retrospective longitudinal case-control study assessed 45 patients with MCA occlusion who exhibited moderate to severe disability (mRS score ≥ 3): 15 underwent EVT and 30 served as controls. Clinical assessments were conducted at two weeks (12-16 days), four weeks (26-30 days), and six months (180-210 days) after stroke onset. Functional assessments comprised the Korean version of the modified Barthel index (MBI), mRS, functional ambulation category (FAC), and dysphagia outcome severity scale (DOSS) to assess disability, handicap, gait, and eating. Results: The MBI, mRS, FAC, and DOSS scores all improved significantly (all p < 0.05) in the EVT group, compared to the controls. Conclusions: EVT has favorable effects on performing routine ADL, the handicap itself, walking, and eating. Therefore, EVT is recommended for patients with acute MCA occlusion, including those with severe disability at the initial assessment.

Microbial signatures of health, gingivitis, and periodontitis.

The subgingival crevice harbors diverse microbial communities. Shifts in the composition of these communities occur with the development of gingivitis and periodontitis, which are considered as successive stages of periodontal health deterioration. It is not clear, however, to what extent health- and gingivitis-associated microbiota are protective, or whether these communities facilitate the successive growth of periodontitis-associated taxa. To further our understanding of the dynamics of the microbial stimuli that trigger disruptions in periodontal homeostasis, we reviewed the available literature with the aim of defining specific microbial signatures associated with different stages of periodontal dysbiosis. Although several studies have evaluated the subgingival communities present in different periodontal conditions, we found limited evidence for the direct comparison of communities in health, gingivitis, and periodontitis. Therefore, we aimed to better define subgingival microbiome shifts by merging and reanalyzing, using unified bioinformatic processing strategies, publicly available 16S ribosomal RNA gene amplicon datasets of periodontal health, gingivitis, and periodontitis. Despite inherent methodological differences across studies, distinct community structures were found for health, gingivitis, and periodontitis, demonstrating the specific associations between gingival tissue status and the subgingival microbiome. Consistent with the concept that periodontal dysbiosis is the result of a process of microbial succession without replacement, more species were detected in disease than in health. However, gingivitis-associated communities were more diverse than those from subjects with periodontitis, suggesting that certain species ultimately become dominant as dysbiosis progresses. We identified the bacterial species associated with each periodontal condition and prevalent species that do not change in abundance from one state to another (core species), and we also outlined species co-occurrence patterns via network analysis. Most periodontitis-associated species were rarely detected in health but were frequently detected, albeit in low abundance, in gingivitis, which suggests that gingivitis and periodontitis are a continuum. Overall, we provide a framework of subgingival microbiome shifts, which can be used to generate hypotheses with respect to community assembly processes and the emergence of periodontal dysbiosis.

A cross-species interaction with a symbiotic commensal enables cell-density-dependent growth and in vivo virulence of an oral pathogen.

Recent studies describe in detail the shifts in composition of human-associated polymicrobial communities from health to disease. However, the specific processes that drive the colonization and overgrowth of pathogens within these communities remain incompletely understood. We used in vitro culture systems and a disease-relevant mouse model to show that population size, which determines the availability of an endogenous diffusible small molecule, limits the growth, colonization, and in vivo virulence of the human oral pathogen Porphyromonas gingivalis. This bacterial pathogen overcomes the requirement for an endogenous cue by utilizing a cell-density dependent, growth-promoting, soluble molecule provided by the symbiotic early colonizer Veillonella parvula, but not produced by other commensals tested. Our work shows that exchange of cell-density-dependent diffusible cues between specific early and late colonizing species in a polymicrobial community drives microbial successions, pathogen colonization and disease development, representing a target process for manipulation of the microbiome towards the healthy state.

Gut commensals, dysbiosis, and immune response imbalance in the pathogenesis of multiple sclerosis.

Intestinal microbiota alterations have been found to be directly related to a wide range of disease states in humans, including multiple sclerosis (MS). The etiology of MS is highly debated and subsequently, there is no cure. Research dedicated to MS and its murine model, experimental autoimmune encephalomyelitis (EAE), have found that dysbiosis of the gut microbiota may play a role in the disease state and severity. In this review, we discuss the characteristic dysbiosis in MS, the role commensal-derived ligands may have in the pathogenesis of the disease, and the possibility of targeting the microbiota as a future therapy.

Homeostasis and Defense at the Surface of the Eye. The Conjunctival Microbiota.

The literature on ocular microbiome has grown tremendously over the past decade, and our knowledge of the different aspects and roles in homeostasis and protection is continuously growing. The development of 16 S rRNA sequencing has allowed the field to characterize communities of bacteria in health and ocular disease. Efforts should continue to further elucidate the interplay between microbiome and key players, such as age, comorbidities, and contact lens usage in order to have better control of the sight-threatening complications.