Identification of amyloidogenic proteins in the microbiomes of a rat Parkinson's disease model and wild‐type rats

Cross seeding between amyloidogenic proteins in the gut is receiving increasing attention as a possible mechanism for initiation or acceleration of amyloid formation by aggregation‐prone proteins such as αSN, which is central in the development of Parkinson''s disease (PD). This is particularly pertinent in view of the growing number of functional (i.e., benign and useful) amyloid proteins discovered in bacteria. Here we identify two amyloidogenic proteins, Pr12 and Pr17, in fecal matter from PD transgenic rats and their wild type counterparts, based on their stability against dissolution by formic acid (FA). Both proteins show robust aggregation into ThT‐positive aggregates that contain higher‐order β‐sheets and have a fibrillar morphology, indicative of amyloid proteins. In addition, Pr17 aggregates formed in vitro showed significant resistance against FA, suggesting an ability to form highly stable amyloid. Treatment with proteinase K revealed a protected core of approx. 9 kDa. Neither Pr12 nor Pr17, however, affected αSN aggregation in vitro. Thus, amyloidogenicity does not per se lead to an ability to cross‐seed fibrillation of αSN. Our results support the use of proteomics and FA to identify amyloidogenic protein in complex mixtures and suggests that there may be numerous functional amyloid proteins in microbiomes.     

The intersection of social determinants of health,the microbiome,and health outcomes in immigrants: A scoping review

In the present scoping review, we explore whether existing evidence supports the premise that social determinants of health (SDoH) affect immigrant health outcomes through their effects on the microbiome. We adapt the National Institute on Minority Health and Health Disparities' research framework to propose a conceptual model that considers the intersection of SDoH, the microbiome, and health outcomes in immigrants. We use this conceptual model as a lens through which to explore recent research about SDoH, biological factors associated with changes to immigrants' microbiomes, and long-term health outcomes. In the 17 articles reviewed, dietary acculturation, physical activity, ethnicity, birthplace, age at migration and length of time in the host country, socioeconomic status, and social/linguistic acculturation were important determinants of postmigration microbiome-related transformations. These factors are associated with progressive shifts in microbiome profile with time in host country, increasing the risks for cardiometabolic, mental, immune, and inflammatory disorders and antibiotic resistance. The evidence thus supports the premise that SDoH influence immigrants' health postmigration, at least in part, through their effects on the microbiome. Omission of important postmigration social-ecological variables (e.g., stress, racism, social/family relationships, and environment), limited research among minoritized subgroups of immigrants, complexity and inter- and intra-individual differences in the microbiome, and limited interdisciplinary and biosocial collaboration restrict our understanding of this area of study. To identify potential microbiome-based interventions and promote immigrants' well-being, more research is necessary to understand the intersections of immigrant health with factors from the biological, behavioral/psychosocial, physical/built environment, and sociocultural environment domains at all social-ecological levels.     

Impaired daily glucocorticoid rhythm in Per1 Brd mice

Biological clocks have evolved in all kinds of organisms in order to anticipate and adjust to the daily light–dark cycle. Within the last decade, the molecular machinery underlying the circadian system was unraveled. In the present study, the impact of the loss of the Per1 or Per2 genes, key components of the core clock oscillator, on body mass, food and water intake, glucose metabolism, and hypothalamic-pituitary-adrenal axis, was investigated in the Per1 ^Brd and Per2 ^Brd mouse models. The results reveal that the lack of Per1 but not Per2 has severe consequences for the regulation of these parameters. Specifically, in Per1 ^Brd animals, we found an impaired daily glucocorticoid rhythm, with markedly elevated levels during the day compared to control animals. In addition, Per1 ^Brd mice showed significant differences in body mass as well as food and water intake. Although the Per1 ^Brd are lighter than wildtype mice, food and water intake per gram body mass is elevated. In addition, the Per1 ^Brd mice exhibit an increased glucose metabolism after i.p. injection with glucose. In conclusion, our study presents first evidence for a link between an altered metabolism in Per1 and Per2 deficient mice, which in the case of the Per1 ^Brd animals might be due to an impaired corticosterone rhythm.     

Social environment and genetics underlie body site‐specific microbiomes of Yellowstone National Park gray wolves (Canis lupus)

The host‐associated microbiome is an important player in the ecology and evolution of species. Despite growing interest in the medical, veterinary, and conservation communities, there remain numerous questions about the primary factors underlying microbiota, particularly in wildlife. We bridged this knowledge gap by leveraging microbial, genetic, and observational data collected in a wild, pedigreed population of gray wolves (Canis lupus) inhabiting Yellowstone National Park. We characterized body site‐specific microbes across six haired and mucosal body sites (and two fecal samples) using 16S rRNA amplicon sequencing. At the phylum level, we found that the microbiome of gray wolves primarily consists of Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, and Proteobacteria, consistent with previous studies within Mammalia and Canidae. At the genus level, we documented body site‐specific microbiota with functions relevant to microenvironment and local physiological processes. We additionally employed observational and RAD sequencing data to examine genetic, demographic, and environmental correlates of skin and gut microbiota. We surveyed individuals across several levels of pedigree relationships, generations, and social groups, and found that social environment (i.e., pack) and genetic relatedness were two primary factors associated with microbial community composition to differing degrees between body sites. We additionally reported body condition and coat color as secondary factors underlying gut and skin microbiomes, respectively. We concluded that gray wolf microbiota resemble similar host species, differ between body sites, and are shaped by numerous endogenous and exogenous factors. These results provide baseline information for this long‐term study population and yield important insights into the evolutionary history, ecology, and conservation of wild wolves and their associated microbes.     

Effects of the GnRH analogue deslorelin implants on reproduction in female domestic cats

The aim of the present study was to investigate the safety and efficacy of deslorelin, a GnRH agonist, implants in suppressing estrus behavior and matings in a controlled ambient environment in feline queens in the presence of a tomcat. Local and utero-ovarian side effects of deslorelin implants were also investigated. The queens were housed in groups and assigned to one of three treatments: group 1 received 9.5 mg deslorelin implants (N = 14), group 2 received 5 mg megestrol acetate tablets and 9.5 mg deslorelin implants (N = 7), and group 3 were given placebo implants (N = 7). All implants were placed subcutaneously cranial to the interscapular region under xylazine hydrochloride sedation. Ovarian activity was monitored by fecal estradiol (E₂) analyses. The animals were observed daily and checked individually at three-day intervals for behavioral signs of estrus. After 18.5 mo of trial, queens were ovariohysterectomized, and ovaries and uteri were weighed and evaluated histologically. E₂ levels were significantly lower in group 1 and 2 than in group 3 with an average of 128.48 ± 19.97 ng/g, 90.44 ± 7.16 ng/g and 283.26 ± 39.21 ng/g, respectively, excepting the first week of treatment. After inserting implants an initial estrus-like increase in fecal E₂ concentrations occurred in all treated queens except one female in group 2. Ovarian and uterine weights were significantly different among the groups (P < 0.01), and were lowest in groups 1 and 2. Primordial and primary follicle numbers were significantly higher in groups 1 and 2 than in group 3 (P < 0.001). Endometrial gland, antral follicle, and corpus luteum (CL) numbers were highest in group 3 (P < 0.01, 0.001, and 0.001, respectively) compared with groups 1 and 2. Deslorelin implants successfully suppressed estrus behavior and E₂ secretion in queens for 18.5 mo of the study period. Further investigations are needed to demonstrate the effects of GnRH agonists on ovarian interstitial tissue.     

Gut microbiota instead of host genotype drive the specificity in the interaction of a natural host-parasite system

Specific interactions between parasite genotypes and host genotypes (G_p × G_h) are commonly found in invertebrate systems, but are largely lacking a mechanistic explanation. The genotype of invertebrate hosts can be complemented by the genomes of microorganisms living on or within the host (‘microbiota’). We investigated whether the bacterial gut microbiota of bumble bees (Bombus terrestris) can account for the specificity of interactions between individuals from different colonies (previously taken as host genotype proxy) and genotypes of the parasite Crithidia bombi. For this, we transplanted the microbiota between individuals of six colonies. Both the general infection load and the specific success of different C. bombi genotypes were mostly driven by the microbiota, rather than by worker genotype. Variation in gut microbiota can therefore be responsible for specific immune phenotypes and the evolution of gut parasites may be driven by interactions with ‘microbiota types’ as well as with host genotypes.     

Architectural design influences the diversity and structure of the built environment microbiome

Buildings are complex ecosystems that house trillions of microorganisms interacting with each other, with humans and with their environment. Understanding the ecological and evolutionary processes that determine the diversity and composition of the built environment microbiome—the community of microorganisms that live indoors—is important for understanding the relationship between building design, biodiversity and human health. In this study, we used high-throughput sequencing of the bacterial 16S rRNA gene to quantify relationships between building attributes and airborne bacterial communities at a health-care facility. We quantified airborne bacterial community structure and environmental conditions in patient rooms exposed to mechanical or window ventilation and in outdoor air. The phylogenetic diversity of airborne bacterial communities was lower indoors than outdoors, and mechanically ventilated rooms contained less diverse microbial communities than did window-ventilated rooms. Bacterial communities in indoor environments contained many taxa that are absent or rare outdoors, including taxa closely related to potential human pathogens. Building attributes, specifically the source of ventilation air, airflow rates, relative humidity and temperature, were correlated with the diversity and composition of indoor bacterial communities. The relative abundance of bacteria closely related to human pathogens was higher indoors than outdoors, and higher in rooms with lower airflow rates and lower relative humidity. The observed relationship between building design and airborne bacterial diversity suggests that we can manage indoor environments, altering through building design and operation the community of microbial species that potentially colonize the human microbiome during our time indoors.     

Host genetic and environmental effects on mouse intestinal microbiota

The mammalian gut harbors complex and variable microbial communities, across both host phylogenetic space and conspecific individuals. A synergy of host genetic and environmental factors shape these communities and account for their variability, but their individual contributions and the selective pressures involved are still not well understood. We employed barcoded pyrosequencing of V1-2 and V4 regions of bacterial small subunit ribosomal RNA genes to characterize the effects of host genetics and environment on cecum assemblages in 10 genetically distinct, inbred mouse strains. Eight of these strains are the foundation of the Collaborative Cross (CC), a panel of mice derived from a genetically diverse set of inbred founder strains, designed specifically for complex trait analysis. Diversity of gut microbiota was characterized by complementing phylogenetic and distance-based, sequence-clustering approaches. Significant correlations were found between the mouse strains and their gut microbiota, reflected by distinct bacterial communities. Cohabitation and litter had a reduced, although detectable effect, and the microbiota response to these factors varied by strain. We identified bacterial phylotypes that appear to be discriminative and strain-specific to each mouse line used. Cohabitation of different strains of mice revealed an interaction of host genetic and environmental factors in shaping gut bacterial consortia, in which bacterial communities became more similar but retained strain specificity. This study provides a baseline analysis of intestinal bacterial communities in the eight CC progenitor strains and will be linked to integrated host genotype, phenotype and microbiota research on the resulting CC panel.     

Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome

Viruses are the most abundant known infectious agents on the planet and are significant drivers of diversity in a variety of ecosystems. Although there have been numerous studies of viral communities, few have focused on viruses within the indigenous human microbiota. We analyzed 2 267 695 virome reads from viral particles and compared them with 263 516 bacterial 16S rRNA gene sequences from the saliva of five healthy human subjects over a 2- to 3-month period, in order to improve our understanding of the role viruses have in the complex oral ecosystem. Our data reveal viral communities in human saliva dominated by bacteriophages whose constituents are temporally distinct. The preponderance of shared homologs between the salivary viral communities in two unrelated subjects in the same household suggests that environmental factors are determinants of community membership. When comparing salivary viromes to those from human stool and the respiratory tract, each group was distinct, further indicating that habitat is of substantial importance in shaping human viromes. Compared with coexisting bacteria, there was concordance among certain predicted host–virus pairings such as Veillonella and Streptococcus, whereas there was discordance among others such as Actinomyces. We identified 122 728 virulence factor homologs, suggesting that salivary viruses may serve as reservoirs for pathogenic gene function in the oral environment. That the vast majority of human oral viruses are bacteriophages whose putative gene function signifies some have a prominent role in lysogeny, suggests these viruses may have an important role in helping shape the microbial diversity in the human oral cavity.     

Co-habiting amphibian species harbor unique skin bacterial communities in wild populations

Although all plant and animal species harbor microbial symbionts, we know surprisingly little about the specificity of microbial communities to their hosts. Few studies have compared the microbiomes of different species of animals, and fewer still have examined animals in the wild. We sampled four pond habitats in Colorado, USA, where multiple amphibian species were present. In total, 32 amphibian individuals were sampled from three different species including northern leopard frogs (Lithobates pipiens), western chorus frogs (Pseudacris triseriata) and tiger salamanders (Ambystoma tigrinum). We compared the diversity and composition of the bacterial communities on the skin of the collected individuals via barcoded pyrosequencing of the 16S rRNA gene. Dominant bacterial phyla included Acidobacteria, Actinobacteria, Bacteriodetes, Cyanobacteria, Firmicutes and Proteobacteria. In total, we found members of 18 bacterial phyla, comparable to the taxonomic diversity typically found on human skin. Levels of bacterial diversity varied strongly across species: L. pipiens had the highest diversity; A. tigrinum the lowest. Host species was a highly significant predictor of bacterial community similarity, and co-habitation within the same pond was not significant, highlighting that the skin-associated bacterial communities do not simply reflect those bacterial communities found in their surrounding environments. Innate species differences thus appear to regulate the structure of skin bacterial communities on amphibians. In light of recent discoveries that some bacteria on amphibian skin have antifungal activity, our finding suggests that host-specific bacteria may have a role in the species-specific resistance to fungal pathogens.