Food webs in food webs: the micro-macro interplay of multilayered networks.

Food webs are typically defined as being macro-organism-based (e.g., plants, mammals, birds) or microbial (e.g., bacteria, fungi, viruses). However, these characterizations have limits. We propose a multilayered food web conceptual model where microbial food webs are nested within food webs composed of macro-organisms. Nesting occurs through host-microbe interactions, which influence the health and behavior of host macro-organisms, such that host microbiomes likely alter population dynamics of interacting macro-organisms and vice versa. Here, we explore the theoretical underpinnings of multilayered food webs and the implications of this new conceptual model on food web ecology. Our framework opens avenues for new empirical investigations into complex ecological networks and provides a new lens through which to view a network's response to ecosystem changes.

Bioenergetic mapping of 'healthy microbiomes' via compound processing potential imprinted in gut and soil metagenomes.

Despite mounting evidence of their importance in human health and ecosystem functioning, the definition and measurement of 'healthy microbiomes' remain unclear. More advanced knowledge exists on health associations for compounds used or produced by microbes. Environmental microbiome exposures (especially via soils) also help shape, and may supplement, the functional capacity of human microbiomes. Given the synchronous interaction between microbes, their feedstocks, and micro-environments, with functional genes facilitating chemical transformations, our objective was to examine microbiomes in terms of their capacity to process compounds relevant to human health. Here we integrate functional genomics and biochemistry frameworks to derive new quantitative measures of in silico potential for human gut and environmental soil metagenomes to process a panel of major compound classes (e.g., lipids, carbohydrates) and selected biomolecules (e.g., vitamins, short-chain fatty acids) linked to human health. Metagenome functional potential profile data were translated into a universal compound mapping 'landscape' based on bioenergetic van Krevelen mapping of function-level meta-compounds and corresponding functional relative abundances, reflecting imprinted genetic capacity of microbiomes to metabolize an array of different compounds. We show that measures of 'compound processing potential' associated with human health and disease (examining atherosclerotic cardiovascular disease, colorectal cancer, type 2 diabetes and anxious-depressive behavior case studies), and displayed seemingly predictable shifts along gradients of ecological disturbance in plant-soil ecosystems (three case studies). Ecosystem quality explained 60-92 % of variation in soil metagenome compound processing potential measures in a post-mining restoration case study dataset. With growing knowledge of the varying proficiency of environmental microbiota to process human health associated compounds, we might design environmental interventions or nature prescriptions to modulate our exposures, thereby advancing microbiota-oriented approaches to human health. Compound processing potential offers a simplified, integrative approach for applying metagenomics in ongoing efforts to understand and quantify the role of microbiota in environmental- and human-health.

The macroecology of butyrate-producing bacteria via metagenomic assessment of butyrate production capacity.

Butyrate-producing bacteria are found in many outdoor ecosystems and host organisms, including humans, and are vital to ecosystem functionality and human health. These bacteria ferment organic matter, producing the short-chain fatty acid butyrate. However, the macroecological influences on their biogeographical distribution remain poorly resolved. Here we aimed to characterise their global distribution together with key explanatory climatic, geographical and physicochemical variables. We developed new normalised butyrate production capacity (BPC) indices derived from global metagenomic (n = 13,078) and Australia-wide soil 16S rRNA (n = 1331) data, using Geographic Information System (GIS) and modelling techniques to detail their ecological and biogeographical associations. The highest median BPC scores were found in anoxic and fermentative environments, including the human (BPC = 2.99) and non-human animal gut (BPC = 2.91), and in some plant-soil systems (BPC = 2.33). Within plant-soil systems, roots (BPC = 2.50) and rhizospheres (BPC = 2.34) had the highest median BPC scores. Among soil samples, geographical and climatic variables had the strongest overall effects on BPC scores (variable importance score range = 0.30-0.03), with human population density also making a notable contribution (variable importance score = 0.20). Higher BPC scores were in soils from seasonally productive sandy rangelands, temperate rural residential areas and sites with moderate-to-high soil iron concentrations. Abundances of butyrate-producing bacteria in outdoor soils followed complex ecological patterns influenced by geography, climate, soil chemistry and hydrological fluctuations. These new macroecological insights further our understanding of the ecological patterns of outdoor butyrate-producing bacteria, with implications for emerging microbially focused ecological and human health policies.

Restoring soil biodiversity.

Soil health is crucial for all terrestrial life, supporting, among other processes, food production, water purification and carbon sequestration. Soil biodiversity - the variety of life within soils - is key to these processes and thus key to soil restoration. Human activities that degrade ecosystems threaten soil biodiversity and associated ecosystem processes. Indeed, 75% of the world's soils are affected by degradation - a figure that could rise to 90% by 2050 if deforestation, overgrazing, urbanisation and other harmful practices persist. Restoring soil biodiversity is a prerequisite for planetary health, and it comes with many challenges and opportunities. Soil directly supports around 60% of all species on Earth, and land degradation poses a major problem for this biodiversity and the ecosystem services that sustain human populations. Indeed, 98% of human calories come from soil, and earthworms alone underpin 6.5% of the world's grain production. Moreover, the total carbon in terrestrial ecosystems is around 3,170 gigatons (1 gigaton (Gt) = 1 billion metric tons), of which approximately 80% (2,500 Gt) is found in soil. Therefore, restoring soil biodiversity is not just a human need but an ecological and Earth-system imperative. It is pivotal for maintaining ecosystem resilience, sustaining agricultural productivity and mitigating climate change impacts.

Childcare centre soil microbiomes are influenced by substrate type and surrounding vegetation condition.

Urban development has profoundly reduced human exposure to biodiverse environments, which is linked to a rise in human disease. The 'biodiversity hypothesis' proposes that contact with diverse microbial communities (microbiota) benefits human health, as exposure to microbial diversity promotes immune training and regulates immune function. Soils and sandpits in urban childcare centres may provide exposure to diverse microbiota that support immunoregulation at a critical developmental stage in a child's life. However, the influence of outdoor substrate (i.e., sand vs. soil) and surrounding vegetation on these environmental microbiota in urban childcare centres remains poorly understood. Here, we used 16S rRNA amplicon sequencing to examine the variation in bacterial communities in sandpits and soils across 22 childcare centres in Adelaide, Australia, plus the impact of plant species richness and habitat condition on these bacterial communities. We show that sandpits had distinct bacterial communities and lower alpha diversity than soils. In addition, we found that plant species richness in the centres' yards and habitat condition surrounding the centres influenced the bacterial communities in soils but not sandpits. These results demonstrate that the diversity and composition of childcare centre sandpit and soil bacterial communities are shaped by substrate type, and that the soils are also shaped by the vegetation within and surrounding the centres. Accordingly, there is potential to modulate the exposure of children to health-associated bacterial communities by managing substrates and vegetation in and around childcare centres.

Probiotic Cities: microbiome-integrated design for healthy urban ecosystems.

Combining microbiome science and biointegrated design offers opportunities to help address the intertwined challenges of urban ecosystem degradation and human disease. Biointegrated materials have the potential to combat superbugs and remediate pollution while inoculating landscape materials with microbiota can promote human immunoregulation and biodiverse green infrastructure, contributing to 'probiotic cities'.

Light-dark cycles may influence in situ soil bacterial networks and diurnally-sensitive taxa.

Soil bacterial taxa have important functional roles in ecosystems (e.g. nutrient cycling, soil formation, plant health). Many factors influence their assembly and regulation, with land cover types (e.g. open woodlands, grasslands), land use types (e.g. nature reserves, urban green space) and plant-soil feedbacks being well-studied factors. However, changes in soil bacterial communities in situ over light-dark cycles have received little attention, despite many plants and some bacteria having endogenous circadian rhythms that could influence soil bacterial communities. We sampled surface soils in situ across 24-h light-dark cycles (at 00:00, 06:00, 12:00, 18:00) at two land cover types (remnant vegetation vs. cleared, grassy areas) and applied 16S rRNA amplicon sequencing to investigate changes in bacterial communities. We show that land cover type strongly affected soil bacterial diversity, with soils under native vegetation expressing 15.4%-16.4% lower alpha diversity but 4.9%-10.6% greater heterogeneity than soils under cleared vegetation. In addition, we report time-dependent and site-specific changes in bacterial network complexity and between 598-922 ASVs showing significant changes in relative abundance across times. Native site node degree (bacterial interactions) at the phylum level was 16.0% higher in the early morning than in the afternoon/evening. Our results demonstrate for the first time that light-dark cycles have subtle yet important effects on soil bacterial communities in situ and that land cover influences these dynamics. We provide a new view of soil microbial ecology and suggest that future studies should consider the time of day when sampling soil bacteria.

Biodiversity and human health: A scoping review and examples of underrepresented linkages.

Mounting evidence supports the connections between exposure to environmental typologies(such as green and blue spaces)and human health. However, the mechanistic links that connect biodiversity (the variety of life) and human health, and the extent of supporting evidence remain less clear. Here, we undertook a scoping review to map the links between biodiversity and human health and summarise the levels of associated evidence using an established weight of evidence framework. Distinct from other reviews, we provide additional context regarding the environment-microbiome-health axis, evaluate the environmental buffering pathway (e.g., biodiversity impacts on air pollution), and provide examples of three under- or minimally-represented linkages. The examples are (1) biodiversity and Indigenous Peoples' health, (2) biodiversity and urban social equity, and (3) biodiversity and COVID-19. We observed a moderate level of evidence to support the environmental microbiota-human health pathway and a moderate-high level of evidence to support broader nature pathways (e.g., greenspace) to various health outcomes, from stress reduction to enhanced wellbeing and improved social cohesion. However, studies of broader nature pathways did not typically include specific biodiversity metrics, indicating clear research gaps. Further research is required to understand the connections and causative pathways between biodiversity (e.g., using metrics such as taxonomy, diversity/richness, structure, and function) and health outcomes. There are well-established frameworks to assess the effects of broad classifications of nature on human health. These can assist future research in linking biodiversity metrics to human health outcomes. Our examples of underrepresented linkages highlight the roles of biodiversity and its loss on urban lived experiences, infectious diseases, and Indigenous Peoples' sovereignty and livelihoods. More research and awareness of these socioecological interconnections are needed.

Return to Play After Surgical Treatment for Acromioclavicular Joint Dislocation: A Systematic Review.

BACKGROUND: Acromioclavicular (AC) joint dislocation is a common clinical problem among young and athletic populations. Surgical management is widely used for high-grade dislocations (Rockwood III-VI) and in high-demand athletes at high risk of recurrence. PURPOSE: To systematically review the evidence in the literature to ascertain the rate and timing of return to play (RTP) and the availability of specific criteria for safe RTP after surgical treatment for AC joint dislocation. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic literature search based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was conducted in the PubMed database. Clinical studies were eligible for inclusion if they reported on RTP after surgical treatment for AC joint dislocation. Statistical analysis was performed with SPSS. RESULTS: We found 120 studies including 4327 cases meeting our inclusion criteria. The majority of patients were male (80.2%), with a mean age of 37.2 years (range, 15-85) and a mean follow-up of 34.5 months. Most were recreational athletes (79%), and the most common sport was cycling. The overall rate of RTP was 91.5%, with 85.6% returning to the same level of play. Among collision athletes, the rate of RTP was 97.3%, with 97.2% returning to the same level of play. In overhead athletes, the rate of RTP was 97.1%, with 79.2% returning to the same level of play. The mean time to RTP was 5.7 months (range, 1.5-15). Specific RTP criteria were reported in the majority of the studies (83.3%); time to return to play was the most commonly reported item (83.3%). Type III Rockwood injuries had the highest RTP rate at 98.7% and the earliest RTP at 4.9 months. Among the different surgical techniques, Kirschner wire fixation had the highest rate of RTP at 98.5%, while isolated graft reconstruction had the earliest RTP at 3.6 months. CONCLUSION: The overall rate of RTP was reportedly high after surgical treatment for AC joint dislocation, with the majority of patients returning to their preinjury levels of sport. There is a lack of consensus in the literature for what constitutes a safe RTP, with further focus on this topic required in future studies.

Policy implications of the microbiota-gut-brain axis.

The microbiota-gut-brain axis facilitates communication between the gut microbiota and the brain. It has implications for health and environmental policy. Microbiota are linked to neurological and metabolic disorders, and our exposure to health-promoting microbiota depends on environmental quality. Microbiota-gut-brain axis interventions could inform policy initiatives to address systemic health issues.

Neuroinflammation in the Dorsal Root Ganglia and Dorsal Horn Contributes to Persistence of Nociceptor Sensitization in SIV-Infected Antiretroviral Therapy-Treated Macaques.

Despite the development of antiretroviral therapy (ART), HIV-associated distal sensory polyneuropathy remains prevalent. Using SIV-infected rhesus macaques, this study examined molecular mechanisms of peripheral and central sensitization to infer chronic pain from HIV infection. Previous studies identified atrophy in nociceptive neurons during SIV infection, which was associated with monocyte infiltration into the dorsal root ganglia (DRG). However, the sensory signaling mechanism connecting this pathology to symptoms remains unclear, especially because pain persists after resolution of high viremia and inflammation with ART. We hypothesized that residual DRG and dorsal horn neuroinflammation contributes to nociceptive sensitization. Using three cohorts of macaques [uninfected (SIV-), SIV-infected (SIV+), and SIV infected with ART (SIV+/ART)], this study showed an increase in the cellular and cytokine inflammatory profiles in the DRG of SIV+/ART macaques compared with uninfected animals. It found significant increase in the expression of nociceptive ion channels, TRPV1, and TRPA1 among DRG neurons in SIV+/ART compared with uninfected animals. SIV-infected and SIV+/ART animals showed reduced innervation of the nonpeptidergic nociceptors into the dorsal horn compared with uninfected animals. Finally, there were a significantly higher number of CD68+ cells in the dorsal horn of SIV+/ART macaques compared with uninfected animals. In summary, these data demonstrate that neuroinflammation, characteristics of nociceptor sensitization, and central terminal atrophy persists in SIV+/ART animals.

Opportunities and challenges for microbiomics in ecosystem restoration.

Microbiomics is the science of characterizing microbial community structure, function, and dynamics. It has great potential to advance our understanding of plant-soil-microbe processes and interaction networks which can be applied to improve ecosystem restoration. However, microbiomics may be perceived as complex and the technology is not accessible to all. The opportunities of microbiomics in restoration ecology are considerable, but so are the practical challenges. Applying microbiomics in restoration must move beyond compositional assessments to incorporate tools to study the complexity of ecosystem recovery. Advances in metaomic tools provide unprecedented possibilities to aid restoration interventions. Moreover, complementary non-omic applications, such as microbial inoculants and biopriming, have the potential to improve restoration objectives by enhancing the establishment and health of vegetation communities.

Transmitted/founder SHIV.D replicates in the brain, causes neuropathogenesis, and persists on combination antiretroviral therapy in rhesus macaques.

A biologically relevant non-human primate (NHP) model of HIV persistence in the central nervous system (CNS) is necessary. Most current NHP/SIV models of HIV infection fail to recapitulate viral persistence in the CNS without encephalitis or fail to employ viruses that authentically represent the ongoing HIV-1 pandemic. Here, we demonstrate viral replication in the brain and neuropathogenesis after combination antiretroviral therapy (ART) in rhesus macaques (RMs) using novel macrophage-tropic transmitted/founder (TF) simian-human immunodeficiency virus SHIV.D.191,859 (SHIV.D). Quantitative immunohistochemistry (IHC) and DNA/RNAscope in situ hybridization (ISH) were performed on three brain regions from six SHIV.D-infected RMs; two necropsied while viremic, two during analytical treatment interruptions, and two on suppressive ART. We demonstrated myeloid-mediated neuroinflammation, viral replication, and proviral DNA in the brain in all animals. These results demonstrate that TF SHIV.D models native HIV-1 CNS replication, pathogenesis, and persistence on ART in rhesus macaques.

Increased Peripheral Inflammation Is Associated With Structural Brain Changes and Reduced Blood Flow in People With Virologically Controlled HIV.

BACKGROUND: While antiretroviral therapy (ART) has improved outcomes for people with HIV (PWH), brain dysfunction is still evident. Immune activation and inflammation remain elevated in PWH receiving ART, thereby contributing to morbidity and mortality. Previous studies demonstrated reduced functional and structural changes in PWH; however, underlying mechanisms remain elusive. METHODS: Our cohort consisted of PWH with ART adherence and viral suppression ( < 50 copies/mL; N = 173). Measurements included immune cell markers of overall immune health (CD4/CD8 T-cell ratio) and myeloid inflammation (CD16+ monocytes), plasma markers of inflammatory status (soluble CD163 and CD14), and structural and functional neuroimaging (volume and cerebral blood flow [CBF], respectively). RESULTS: Decreased CD4/CD8 ratios correlated with reduced brain volume, and higher levels of inflammatory CD16+ monocytes were associated with reduced brain volume in total cortex and gray matter. An increase in plasma soluble CD14-a marker of acute peripheral inflammation attributed to circulating microbial products-was associated with reduced CBF within the frontal, parietal, temporal, and occipital cortices and total gray matter. CONCLUSIONS: CD4/CD8 ratio and number of CD16+ monocytes, which are chronic immune cell markers, are associated with volumetric loss in the brain. Additionally, this study shows a potential new association between plasma soluble CD14 and CBF.

The aerobiome-health axis: a paradigm shift in bioaerosol thinking.

Historically, a primary aim of bioaerosol research has been to understand and prevent 'unhealthy' human exposures to pathogens and allergens. However, there has been a recent paradigm shift in thinking about bioaerosols. Exposure to a diverse aerobiome - the microbiome of the air - is now considered necessary to be healthy.

Osteopontin Is an Integral Mediator of Cardiac Interstitial Fibrosis in Models of Human Immunodeficiency Virus Infection.

BACKGROUND: People with human immunodeficiency virus (HIV) have heightened incidence/risk of diastolic dysfunction and heart failure. Women with HIV have elevated cardiac fibrosis, and plasma osteopontin (Opn) is correlated to cardiac pathology. Therefore, this study provides mechanistic insight into the relationship between osteopontin and cardiac fibrosis during HIV infection. METHODS: Mouse embryonic fibroblasts (MEFs) modeled cardiac fibroblasts in vitro. Simian immunodeficiency virus (SIV)-infected macaques with or without antiretroviral therapy and HIV-infected humanized mice modeled HIV-associated cardiac fibrosis. RESULTS: Lipopolysaccharide-stimulated MEFs were myofibroblast-like, secreted cytokines, and produced Opn transcripts. SIV-infected animals had elevated plasma Opn at necropsy, full-length Opn in the ventricle, and ventricular interstitial fibrosis. Regression modeling identified growth differentiation factor 15, CD14+CD16+ monocytes, and CD163 expression on CD14+CD16+ monocytes as independent predictors of plasma Opn during SIV infection. HIV-infected humanized mice showed increased interstitial fibrosis compared to uninfected/untreated animals, and systemic inhibition of osteopontin by RNA aptamer reduced left ventricle fibrosis in HIV-infected humanized mice. CONCLUSIONS: Since Opn is elevated in the plasma and left ventricle during SIV infection and systemic inhibition of Opn reduced cardiac fibrosis in HIV-infected mice, Opn may be a potential target for adjunctive therapies to reduce cardiac fibrosis in people with HIV.

Antiretroviral Therapy Ameliorates Simian Immunodeficiency Virus-Associated Myocardial Inflammation by Dampening Interferon Signaling and Pathogen Response in the Heart.

People with human immunodeficiency virus have an increased risk of developing cardiovascular disease. RNA-Seq was performed on hearts from simian immunodeficiency virus (SIV)-infected rhesus macaques with or without antiretroviral therapy (ART). SIV infection led to high plasma viral load with very little myocardial viral RNA. SIV infection promoted an inflammatory environment in the heart through interferon and pathogen signaling, in the absence of myocardial viral RNA. While ART dampened interferon and cytokine response in the heart, SIV-infected animals receiving ART had deficits in the expression of genes directly involved in fatty acid metabolism relative to SIV-uninfected animals.

Treatment options for acute Rockwood type III-V acromioclavicular dislocations: a network meta-analysis of randomized controlled trials.

BACKGROUND: Acute Rockwood type III-V acromioclavicular (AC) dislocations have been treated with numerous surgical techniques over the years. The purpose of this study was to perform a network meta-analysis (NMA) of randomized controlled trials to quantitatively define the optimal treatment for AC dislocations requiring operative treatment. METHODS: A literature search of 3 databases was performed based on Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Randomized controlled trials comparing 1 of 10 treatments for acute Rockwood type III-V AC dislocations-nonoperative treatment, Kirschner wire fixation (KW), coracoclavicular screw fixation (Scr), hook plate (HP), open coracoclavicular cortical button (CBO), arthroscopic coracoclavicular cortical button (CBA), ≥2 coracoclavicular cortical buttons (CB2), isolated graft reconstruction (GR), cortical button with graft augmentation (CB-GR), and coracoclavicular and acromioclavicular fixation (AC)-were included. Clinical outcomes were compared using a frequentist approach to NMA, with statistical analysis performed using the R program. Treatment options were ranked using the P-score, which estimates the likelihood that the investigated treatment is the ideal method for an optimal result in each outcome measure on a scale from 0 to 1. RESULTS: Of 5362 reviewed studies, 26 met the inclusion criteria, with a total of 1581 patients included in the NMA. AC, CB-GR, GR, CB2, CBA, and CBO demonstrated superiority over HP, Scr, KW, and nonoperative treatment at final follow-up for the Constant-Murley score and Disabilities of the Arm, Shoulder and Hand score, with AC and CB-GR showing the highest P-scores for the Constant-Murley score (0.957 and 0.781, respectively) and GR and CBO showing the highest P-scores for the Disabilities of the Arm, Shoulder and Hand score (0.896 and 0.750, respectively). GR had the highest P-score for the visual analog scale score (0.986). HP, CB2, CB-GR, AC, CBA, and CBO demonstrated superiority in the coracoclavicular distance (CCD) and recurrence at final follow-up, with HP and CB2 having the highest P-scores for the CCD (0.798 and 0.757, respectively) and with GR and CB-GR having the highest P-scores for recurrence (0.880 and 0.855, respectively). KW and Scr showed the shortest operative times (P-scores of 0.917 and 0.810, respectively), whereas GR and CBA showed the longest operative times (P-scores of 0.120 and 0.097, respectively). CONCLUSIONS: Although there are multiple fixation options for acute Rockwood type III-V AC dislocations, adding AC fixation or graft augmentation likely improves functional outcomes and decreases the CCD and recurrence rate at final follow-up-at the expense of longer operative times.

Plasma osteopontin relates to myocardial fibrosis and steatosis and to immune activation among women with HIV.

OBJECTIVE: Women with HIV (WWH) have heightened heart failure risk. Plasma OPN (osteopontin) is a powerful predictor of heart failure outcomes in the general population. Limited data exist on relationships between plasma OPN and surrogates of HIV-associated heart failure risk. DESIGN: Prospective, cross-sectional. METHODS: We analyzed relationships between plasma OPN and cardiac structure/function (assessed using cardiovascular magnetic resonance imaging) and immune activation (biomarkers and flow cytometry) among 20 WWH and 14 women without HIV (WWOH). RESULTS: Plasma OPN did not differ between groups. Among WWH, plasma OPN related directly to the markers of cardiac fibrosis, growth differentiation factor-15 (ρ = 0.51, P = 0.02) and soluble interleukin 1 receptor-like 1 (ρ = 0.45, P = 0.0459). Among WWH (but not among WWOH or the whole group), plasma OPN related directly to both myocardial fibrosis (ρ = 0.49, P = 0.03) and myocardial steatosis (ρ = 0.46, P = 0.0487). Among the whole group and WWH (and not among WWOH), plasma OPN related directly to the surface expression of C-X3-C motif chemokine receptor 1 (CX3CR1) on nonclassical (CD14-CD16+) monocytes (whole group: ρ = 0.36, P = 0.04; WWH: ρ = 0.46, P = 0.04). Further, among WWH and WWOH (and not among the whole group), plasma OPN related directly to the surface expression of CC motif chemokine receptor 2 (CCR2) on inflammatory (CD14+CD16+) monocytes (WWH: ρ = 0.54, P = 0.01; WWOH: ρ = 0.60, P = 0.03), and in WWH, this held even after controlling for HIV-specific parameters. CONCLUSION: Among WWH, plasma OPN, a powerful predictor of heart failure outcomes, related to myocardial fibrosis and steatosis and the expression of CCR2 and CX3CR1 on select monocyte subpopulations. OPN may play a role in heart failure pathogenesis among WWH. CLINICALTRIALSGOV REGISTRATION: NCT02874703.