Microbial transmission in the social microbiome and host health and disease.

Although social interactions are known to drive pathogen transmission, the contributions of socially transmissible host-associated mutualists and commensals to host health and disease remain poorly explored. We use the concept of the social microbiome-the microbial metacommunity of a social network of hosts-to analyze the implications of social microbial transmission for host health and disease. We investigate the contributions of socially transmissible microbes to both eco-evolutionary microbiome community processes (colonization resistance, the evolution of virulence, and reactions to ecological disturbance) and microbial transmission-based processes (transmission of microbes with metabolic and immune effects, inter-specific transmission, transmission of antibiotic-resistant microbes, and transmission of viruses). We consider the implications of social microbial transmission for communicable and non-communicable diseases and evaluate the importance of a socially transmissible component underlying canonically non-communicable diseases. The social transmission of mutualists and commensals may play a significant, under-appreciated role in the social determinants of health and may act as a hidden force in social evolution.

Female behavior drives the formation of distinct social structures in C57BL/6J versus wild-derived outbred mice in field enclosures.

BACKGROUND: Social behavior and social organization have major influences on individual health and fitness. Yet, biomedical research focuses on studying a few genotypes under impoverished social conditions. Understanding how lab conditions have modified social organizations of model organisms, such as lab mice, relative to natural populations is a missing link between socioecology and biomedical science. RESULTS: Using a common garden design, we describe the formation of social structure in the well-studied laboratory mouse strain, C57BL/6J, in replicated mixed-sex populations over 10-day trials compared to control trials with wild-derived outbred house mice in outdoor field enclosures. We focus on three key features of mouse social systems: (i) territory establishment in males, (ii) female social relationships, and (iii) the social networks formed by the populations. Male territorial behaviors were similar but muted in C57 compared to wild-derived mice. Female C57 sharply differed from wild-derived females, showing little social bias toward cage mates and exploring substantially more of the enclosures compared to all other groups. Female behavior consistently generated denser social networks in C57 than in wild-derived mice. CONCLUSIONS: C57 and wild-derived mice individually vary in their social and spatial behaviors which scale to shape overall social organization. The repeatable societies formed under field conditions highlights opportunities to experimentally study the interplay between society and individual biology using model organisms.

The microbiome: A heritable contributor to bone morphology?

Bone provides structure to the vertebrate body that allows for movement and mechanical stimuli that enable and the proper development of neighboring organs. Bone morphology and density is also highly heritable. In humans, heritability of bone mineral density has been estimated to be 50-80%. However, genome wide association studies have so far explained only 25% of the variation in bone mineral density, suggesting that a substantial portion of the heritability of bone mineral density may be due to environmental factors. Here we explore the idea that the gut microbiome is a heritable environmental factor that contributes to bone morphology and density. The vertebrae skeleton has evolved over the past ~500 million years in the presence of commensal microbial communities. The composition of the commensal microbial communities has co-evolved with the hosts resulting in species-specific microbial populations associated with vertebrate phylogeny. Furthermore, a substantial portion of the gut microbiome is acquired through familial transfer. Recent studies suggest that the gut microbiome also influences postnatal development. Here we review studies from the past decade in mice that have shown that the presence of the gut microbiome can influence postnatal bone growth regulating bone morphology and density. These studies indicate that the presence of the gut microbiome may increase longitudinal bone growth and appositional bone growth, resulting differences cortical bone morphology in long bones. More surprising, however are recent studies showing that transfer of the gut microbiota among inbred mouse strains with distinct bone phenotypes can alter postnatal development and adult bone morphology. Together these studies support the concept that the gut microbiome is a contributor to skeletal phenotype.

Removal of sequencing adapter contamination improves microbial genome databases.

Advances in assembling microbial genomes have led to growth of reference genome databases, which have been transformative for applied and basic microbiome research. Here we show that published microbial genome databases from humans, mice, cows, pigs, fish, honeybees, and marine environments contain significant sequencing-adapter contamination that systematically reduces assembly accuracy and contiguousness. By removing the adapter-contaminated ends of contiguous sequences and reassembling MGnify reference genomes, we improve the quality of assemblies in these databases.

Convergence of gut microbiota in myrmecophagous amphibians.

The gut microbiome composition of terrestrial vertebrates is known to converge in response to common specialized dietary strategies, like leaf-eating (folivory) or ant- and termite-eating (myrmecophagy). To date, such convergence has been studied in mammals and birds, but has been neglected in amphibians. Here, we analysed 15 anuran species (frogs and toads) representing five Neotropical families and demonstrated the compositional convergence of the gut microbiomes of distantly related myrmecophagous species. Specifically, we found that the gut microbial communities of bufonids and microhylids, which have independently evolved myrmecophagy, were significantly more similar than expected based on their hosts' evolutionary divergence. Conversely, we found that gut microbiome composition was significantly associated with host evolutionary history in some cases. For instance, the microbiome composition of Xenohyla truncata, one of the few known amphibians that eat fruits, was not different from those of closely related tree frogs with an arthropod generalist diet. Bacterial taxa overrepresented in myrmecophagous species relative to other host families include Paludibacter, Treponema, and Rikenellaceae, suggesting diet-mediated selection and prey-to-predator transmission likely driving the observed compositional convergence. This study provides a basis for examining the roles of the gut microbiome in host tolerance and sequestration of toxic alkaloids from ants and termites.

Metagenomic signatures of balancing selection in the human gut.

Bacterial lineages that populate the human gut microbiota contend with spatial and temporal fluctuations in numerous environmental variables, including bouts of extreme selective agents such as antibiotics. Oscillations in the adaptive landscape can impose balancing selection on populations, leaving characteristic signatures in the sequence variation of functionally significant genomic loci. Despite their potential importance for gut bacterial adaptation, the metagenomic targets of balancing selection have not been identified. Here, I present population genetic evidence that balancing selection maintains allelic diversity in multidrug efflux pumps of multiple predominant gut bacterial species. Metagenome-wide scans of 566,958 genes from 287 bacterial species represented by 118,617 metagenome-assembled genomes indicated that most genes have been conserved by purifying selection. However, dozens of core open reading frames (CORFs) displayed positive Tajima's D values that deviated significantly from their species' genomic backgrounds, indicating the action of balancing selection. Multidrug efflux pumps (MEPs) from a diversity of bacterial species were significantly enriched among the CORFs with Tajima's D values >3 in industrialized, but not nonindustrialized, human populations. The AcrB subunit of an MEP from Bacteroides dorei displayed the highest Tajima's D of any CORF. Divergent haplotypes of this CORF displayed evidence of positive selection and homology to an Escherichia coli AcrB subunit that binds tetracycline and macrolide antibiotics, suggesting functional significance and implicating medical antibiotics as an agent of selection acting on this locus. Other proteins identified as targets of balancing selection included peptidoglycan/LPS O-acetylases and ion transporters. Intriguingly, the degree of balancing selection acting on gut bacterial species was associated with species abundance in the gut based on metagenomic data, further suggesting fitness benefits of the allelic variation identified.

Assessing co-diversification in host-associated microbiomes.

When lineages of hosts and microbial symbionts engage in intimate interactions over evolutionary timescales, they can diversify in parallel (i.e., co-diversify), producing associations between the lineages' phylogenetic histories. Tests for co-diversification of individual microbial lineages and their hosts have been developed previously, and these have been applied to discover ancient symbioses in diverse branches of the tree of life. However, most host-microbe relationships are not binary but multipartite, in that a single host-associated microbiota can contain many microbial lineages, generating challenges for assessing co-diversification. Here, we review recent evidence for co-diversification in complex microbiota, highlight the limitations of prior studies, and outline a hypothesis testing approach designed to overcome some of these limitations. We advocate for the use of microbiota-wide scans for co-diversifying symbiont lineages and discuss tools developed for this purpose. Tests for co-diversification for simple host symbiont systems can be extended to entire phylogenies of microbial lineages (e.g., metagenome-assembled or isolate genomes, amplicon sequence variants) sampled from host clades, thereby providing a means for identifying co-diversifying symbionts present within complex microbiota. The relative ages of symbiont clades can corroborate co-diversification, and multi-level permutation tests can account for multiple comparisons and phylogenetic non-independence introduced by repeated sampling of host species. Discovering co-diversifying lineages will generate powerful opportunities for interrogating the molecular evolution and lineage turnover of ancestral, host-species specific symbionts within host-associated microbiota.

Predictable and host-species specific humanization of the gut microbiota in captive primates.

Humans and nonhuman primates (NHPs) harbor complex gut microbial communities that affect phenotypes and fitness. The gut microbiotas of wild NHPs reflect their hosts' phylogenetic histories and are compositionally distinct from those of humans, but in captivity the endogenous gut microbial lineages of NHPs can be lost or replaced by lineages found in humans. Despite its potential contributions to gastrointestinal dysfunction, this humanization of the gut microbiota has not been investigated systematically across captive NHP species. Here, we show through comparisons of well-sampled wild and captive populations of apes and monkeys that the fraction of the gut microbiota humanized by captivity varies significantly between NHP species but is remarkably reproducible between captive populations of the same NHP species. Conspecific captive populations displayed significantly greater than expected overlap in the sets of bacterial 16S rRNA gene variants that were differentially abundant between captivity and the wild. This overlap was evident even between captive populations residing on different continents but was never observed between heterospecific captive populations. In addition, we developed an approach incorporating human gut microbiota data to rank NHPs' gut microbial clades based on the propensity of their lineages to be lost or replaced in captivity by lineages found in humans. Relatively few microbial genera displayed reproducible degrees of humanization in different captive host species, but most microbial genera were reproducibly humanized or retained from the wild in conspecific pairs of captive populations. These results demonstrate that the gut microbiotas of captive NHPs display predictable, host-species specific responses to captivity.

Clinical Conundrum: To Deliver or Not To Deliver a Patient With Pulmonary Edema and Preeclampsia.

While admitted for management of hyperemesis gravidarum and preeclampsia, a 29-year-old gravida 1 para 0 patient with type 1 diabetes mellitus developed acute shortness of breath at 24 weeks gestation. Physical examination and chest X-ray findings were consistent with pulmonary edema, which in pregnancy is most often a severe complication of preeclampsia warranting delivery. The case is discussed with respect to diagnosis and management of pulmonary edema and acquired pulmonary hypertension in pregnancy, including timing and mode of delivery. Many case studies and guidelines advise caution when embarking on pregnancy with primary pulmonary hypertension; however, there is little available to guide clinical management when pulmonary hypertension secondary to fluid overload and preeclampsia develops during pregnancy.

The Lizard Gut Microbiome Changes with Temperature and Is Associated with Heat Tolerance.

Vertebrates harbor trillions of microorganisms in the gut, collectively termed the gut microbiota, which affect a wide range of host functions. Recent experiments in lab-reared vertebrates have shown that changes in environmental temperature can induce shifts in the gut microbiota, and in some cases these shifts have been shown to affect host thermal physiology. However, there is a lack of information about the effects of temperature on the gut microbiota of wild-caught vertebrates. Moreover, in ectotherms, which are particularly vulnerable to changing temperature regimens, the extent to which microbiota composition is shaped by temperature and associated with host thermal tolerance has not been investigated. To address these issues, we monitored the gut microbiota composition of wild-caught western fence lizards (Sceloporus occidentalis) experimentally exposed to a cool-to-warm temperature transition. Comparing experimentally exposed and control lizards indicated that warm temperatures altered and destabilized the composition of the S. occidentalis gut microbiota. Warming drove a significant reduction in the relative abundances of a clade of Firmicutes, a significant increase in the rate of compositional turnover in the gut microbiota within individual lizards, and increases in the abundances of bacteria from predicted pathogenic clades. In addition, the composition of the microbiota was significantly associated with the thermal tolerance of lizards measured at the end of the experiment. These results suggest that temperature can alter the lizard gut microbiota, with potential implications for the physiological performance and fitness of natural populations.IMPORTANCE Gut microbial communities affect their animal hosts in numerous ways, motivating investigations of the factors that shape the gut microbiota and the consequences of gut microbiota variation for host traits. In this study, we tested the effects of increases in environmental temperatures on the gut microbiota of fence lizards, a vertebrate ectotherm threatened by warming climates. By monitoring lizards and their gut microbes during an experimental temperature treatment, we showed that the warming altered and destabilized the lizard gut microbiota. Moreover, measuring thermal performance of lizard hosts at the end of the experiment indicated that the composition of the gut microbiota was associated with host thermal tolerance. These results indicate that warming temperatures can alter the gut microbiota of vertebrate ectotherms and suggest relationships between variation in the gut microbiota and the thermal physiology of natural host populations.

Dispersal limitation promotes the diversification of the mammalian gut microbiota.

The gut bacterial communities of mammals have profound effects on host fitness, but the processes that generate and maintain gut bacterial diversity remain poorly understood. We mapped compositional variation (i.e., ß-diversity) in the gut microbiotas of 136 pairs of wild mammalian species living throughout the Americas to assess how the distribution of mammals across geographic space influences the diversification of their gut bacteria. Comparing the gut microbiotas of sympatric and allopatric mammalian populations provided insights into the flow of gut bacteria within and between mammalian communities, revealing that spatial limits on bacterial dispersal promote ß-diversity between the gut microbiotas of mammalian species. Each geographic locale displayed a unique gut-microbiota composition that could not be fully explained by the diets and phylogenetic histories of the resident mammalian hosts, indicating that some gut bacteria are geographically restricted. Across the western hemisphere, the compositional overlap between the gut microbiotas of allopatric mammalian populations decayed exponentially with the geographic distance separating the hosts. The relationship between geographic distances among hosts and compositional differences among their gut microbiotas was independent of dietary and phylogenetic divergence among hosts. Within mammalian communities, we observed widespread sharing of gut bacteria between predator-prey host-species pairs, indicating horizontal transfer of gut bacteria through mammalian food chains. Collectively, these results indicate that compositional differences between the gut microbiotas of mammalian taxa are generated and maintained by limits to bacterial dispersal imposed by physical distance between hosts.

Where next for microbiome research?

The development of high-throughput sequencing technologies has transformed our capacity to investigate the composition and dynamics of the microbial communities that populate diverse habitats. Over the past decade, these advances have yielded an avalanche of metagenomic data. The current stage of "van Leeuwenhoek"-like cataloguing, as well as functional analyses, will likely accelerate as DNA and RNA sequencing, plus protein and metabolic profiling capacities and computational tools, continue to improve. However, it is time to consider: what's next for microbiome research? The short pieces included here briefly consider the challenges and opportunities awaiting microbiome research.

Destabilization of the gut microbiome marks the end-stage of simian immunodeficiency virus infection in wild chimpanzees.

Enteric dysbiosis is a characteristic feature of progressive human immunodeficiency virus type 1 (HIV-1) infection but has not been observed in simian immunodeficiency virus (SIVmac)-infected macaques, including in animals with end-stage disease. This has raised questions concerning the mechanisms underlying the HIV-1 associated enteropathy, with factors other than virus infection, such as lifestyle and antibiotic use, implicated as playing possible causal roles. Simian immunodeficiency virus of chimpanzees (SIVcpz) is also associated with increased mortality in wild-living communities, and like HIV-1 and SIVmac, can cause CD4+ T cell depletion and immunodeficiency in infected individuals. Given the central role of the intestinal microbiome in mammalian health, we asked whether gut microbial constituents could be identified that are indicative of SIVcpz status and/or disease progression. Here, we characterized the gut microbiome of SIVcpz-infected and -uninfected chimpanzees in Gombe National Park, Tanzania. Subjecting a small number of fecal samples (N = 9) to metagenomic (shotgun) sequencing, we found bacteria of the family Prevotellaceae to be enriched in SIVcpz-infected chimpanzees. However, 16S rRNA gene sequencing of a larger number of samples (N = 123) failed to show significant differences in both the composition and diversity (alpha and beta) of gut bacterial communities between infected (N = 24) and uninfected (N = 26) chimpanzees. Similarly, chimpanzee stool-associated circular virus (Chi-SCV) and chimpanzee adenovirus (ChAdV) identified by metagenomic sequencing were neither more prevalent nor more abundant in SIVcpz-infected individuals. However, fecal samples collected from SIVcpz-infected chimpanzees within 5 months before their AIDS-related death exhibited significant compositional changes in their gut bacteriome. These data indicate that SIVcpz-infected chimpanzees retain a stable gut microbiome throughout much of their natural infection course, with a significant destabilization of bacterial (but not viral) communities observed only in individuals with known immunodeficiency within the last several months before their death. Am. J. Primatol. 80:e22515, 2018. © 2015 Wiley Periodicals, Inc.

Rapid changes in the gut microbiome during human evolution.

Humans are ecosystems containing trillions of microorganisms, but the evolutionary history of this microbiome is obscured by a lack of knowledge about microbiomes of African apes. We sequenced the gut communities of hundreds of chimpanzees, bonobos, and gorillas and developed a phylogenetic approach to reconstruct how present-day human microbiomes have diverged from those of ancestral populations. Compositional change in the microbiome was slow and clock-like during African ape diversification, but human microbiomes have deviated from the ancestral state at an accelerated rate. Relative to the microbiomes of wild apes, human microbiomes have lost ancestral microbial diversity while becoming specialized for animal-based diets. Individual wild apes cultivate more phyla, classes, orders, families, genera, and species of bacteria than do individual humans across a range of societies. These results indicate that humanity has experienced a depletion of the gut flora since diverging from Pan.

Sympatric chimpanzees and gorillas harbor convergent gut microbial communities.

The gut microbial communities within great apes have been shown to reflect the phylogenetic history of their hosts, indicating codiversification between great apes and their gut microbiota over evolutionary timescales. But because the great apes examined to date represent geographically isolated populations whose diets derive from different sources, it is unclear whether this pattern of codiversification has resulted from a long history of coadaptation between microbes and hosts (heritable factors) or from the ecological and geographic separation among host species (environmental factors). To evaluate the relative influences of heritable and environmental factors on the evolution of the great ape gut microbiota, we assayed the gut communities of sympatric and allopatric populations of chimpanzees, bonobos, and gorillas residing throughout equatorial Africa. Comparisons of these populations revealed that the gut communities of different host species can always be distinguished from one another but that the gut communities of sympatric chimpanzees and gorillas have converged in terms of community composition, sharing on average 53% more bacterial phylotypes than the gut communities of allopatric hosts. Host environment, independent of host genetics and evolutionary history, shaped the distribution of bacterial phylotypes across the Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria, the four most common phyla of gut bacteria. Moreover, the specific patterns of phylotype sharing among hosts suggest that chimpanzees living in sympatry with gorillas have acquired bacteria from gorillas. These results indicate that geographic isolation between host species has promoted the evolutionary differentiation of great ape gut bacterial communities.

Resident duty hour modification affects perceptions in medical education, general wellness, and ability to provide patient care.

BACKGROUND: Resident duty hours have recently been under criticism, with concerns for resident and patient well-being. Historically, call shifts have been long, and some residency training programs have now restricted shift lengths. Data and opinions about the effects of such restrictions are conflicting. The Internal Medicine Residency Program at Dalhousie University recently moved from a traditional call structure to a day float/night float system. This study evaluated how this change in duty hours affected resident perceptions in several key domains. METHODS: Senior residents from an internal medicine training program in Canada responded to an anonymous online survey immediately before and 6 months after the implementation of duty hour reform. The survey contained questions relating to three major domains: resident wellness, ability to deliver quality health care, and medical education experience. Mean pre- and post-intervention scores were compared using the t-test for paired samples. RESULTS: Twenty-three of 27 (85 %) senior residents completed both pre- and post-reform surveys. Residents perceived significant changes in many domains with duty hour reform. These included improved general wellness, less exposure to personal harm, fewer feelings of isolation, less potential for error, improvement in clinical skills expertise, increased work efficiency, more successful teaching, increased proficiency in medical skills, more successful learning, and fewer rotation disruptions. CONCLUSIONS: Senior residents in a Canadian internal medicine training program perceived significant benefits in medical education experience, ability to deliver healthcare, and resident wellness after implementation of duty hour reform.

Pregnancy-induced remodeling of heart valves.

Recent studies have demonstrated remodeling of aortic and mitral valves leaflets under the volume loading and cardiac expansion of pregnancy. Those valves' leaflets enlarge with altered collagen fiber architecture, content, and cross-linking and biphasic changes (decreases, then increases) in extensibility during gestation. This study extends our analyses to right-sided valves, with additional compositional measurements for all valves. Valve leaflets were harvested from nonpregnant heifers and pregnant cows. Leaflet structure was characterized by leaflet dimensions, and ECM composition was determined using standard biochemical assays. Histological studies assessed changes in cellular and ECM components. Leaflet mechanical properties were assessed using equibiaxial mechanical testing. Collagen thermal stability and cross-linking were assessed using denaturation and hydrothermal isometric tension tests. Pulmonary and tricuspid leaflet areas increased during pregnancy by 35 and 55%, respectively. Leaflet thickness increased by 20% only in the pulmonary valve and largely in the fibrosa (30% thickening). Collagen crimp length was reduced in both the tricuspid (61%) and pulmonary (42%) valves, with loss of crimped area in the pulmonary valve. Thermomechanics showed decreased collagen thermal stability with surprisingly maintained cross-link maturity. The pulmonary leaflet exhibited the biphasic change in extensibility seen in left side valves, whereas the tricuspid leaflet mechanics remained largely unchanged throughout pregnancy. The tricuspid valve exhibits a remodeling response during pregnancy that is significantly diminished from the other three valves. All valves of the heart remodel in pregnancy in a manner distinct from cardiac pathology, with much similarity valve to valve, but with interesting valve-specific responses in the aortic and tricuspid valves.