Investigating the impact of condomless vaginal intercourse and lubricant use on the vaginal metabolome: a pre-post observational study.

OBJECTIVE: The vaginal metabolome is a significant factor in the vaginal microenvironment, and data are emerging on its independent role in urogenital health. Condomless vaginal intercourse and personal lubricant use are common practices that may affect the vaginal metabolome. The aim of the present study is to describe the associations between condomless intercourse and lubricant use on the vaginal metabolome. METHODS: This study used archived mid-vaginal swabs from a 10-week observational cohort of reproductive age women who self-collected samples and recorded behavioural diaries daily. Cases and controls were defined as participants who self-reported condomless vaginal intercourse with or without lubricant use, respectively. Samples were drawn prior to and following condomless vaginal intercourse. Twenty-two case participants were race/ethnicity matched to 22 control participants. Mid-vaginal swabs were subjected to 16S rRNA gene amplicon sequencing and untargeted ultrahigh performance liquid chromatography tandem mass spectroscopy metabolomics. Bayesian mixed-effects regression (unadjusted and adjusted for the vaginal microbiota) was used to evaluate differences in metabolite concentration associated with vaginal intercourse and lubricant use. RESULTS: Both condomless penile-vaginal intercourse and lubricant use were independently associated with higher (up to 8.3-fold) concentrations of metabolites indicative of epithelial damage (eg, sarcosine) and many host-produced antioxidants. Lubricant use was significantly associated with increases in lipids related to cellular damage, host-produced sphingolipids (antimicrobials), antioxidants and salicylate, a cooling agent common to lubricants, in a study design which controls for the independent effect of intercourse. Metabolites involved in oxidative stress and salicylate were strongly correlated with several molecular bacterial vaginosis-associated bacteria. CONCLUSIONS: This study provides important foundational data on how condomless vaginal-penile intercourse and lubricant use affect the vaginal metabolome and may affect the protective mechanisms in the vaginal microenvironment.

Bacterial Vaginosis Monitoring with Carbon Nanotube Field-Effect Transistors.

The ability to rapidly and reliably screen for bacterial vaginosis (BV) during pregnancy is of great significance for maternal health and pregnancy outcomes. In this proof-of-concept study, we demonstrated the potential of carbon nanotube field-effect transistors (NTFET) in the rapid diagnostics of BV with the sensing of BV-related factors such as pH and biogenic amines. The fabricated sensors showed good linearity to pH changes with a linear correlation coefficient of 0.99. The pH sensing performance was stable after more than one month of sensor storage. In addition, the sensor was able to classify BV-related biogenic amine-negative/positive samples with machine learning, utilizing different test strategies and algorithms, including linear discriminant analysis (LDA), support vector machine (SVM), and principal component analysis (PCA). The biogenic amine sample status could be well classified using a soft-margin SVM model with a validation accuracy of 87.5%. The accuracy could be further improved using a gold gate electrode for measurement, with accuracy higher than 90% in both LDA and SVM models. We also explored the sensing mechanisms and found that the change in NTFET off current was crucial for classification. The fabricated sensors successfully detect BV-related factors, demonstrating the competitive advantage of NTFET for point-of-care diagnostics of BV.

Perceived Stress and Molecular Bacterial Vaginosis in the National Institutes of Health Longitudinal Study of Vaginal Flora.

Vaginal microbiota provide the first line of defense against urogenital infections primarily through protective actions of Lactobacillus species Perceived stress increases susceptibility to infection through several mechanisms, including suppression of immune function. We investigated whether stress was associated with deleterious changes to vaginal bacterial composition in a subsample of 572 women in the Longitudinal Study of Vaginal Flora, sampled from 1999 through 2002. Using Cox proportional hazards models, both unadjusted and adjusted for sociodemographic factors and sexual behaviors, we found that participants who exhibited a 5-unit-increase in Cohen's Perceived Stress Scale had greater risk (adjusted hazard ratio (HR) = 1.40, 95% confidence interval (CI): 1.13, 1.74) of developing molecular bacterial vaginosis (BV), a state with low Lactobacillus abundance and diverse anaerobic bacteria. A 5-unit increase in stress score was also associated with greater risks of transitioning from the L. iners-dominated community state type (26% higher) to molecular-BV (adjusted HR = 1.26, 95% CI: 1.01, 1.56) or maintaining molecular-BV from baseline (adjusted HR = 1.23, 95% CI: 1.01, 1.47). Inversely, women with baseline molecular-BV reporting a 5-unit stress increase were less likely to transition to microbiota dominated by L. crispatus, L. gasseri, or L. jensenii (adjusted HR = 0.81, 95% CI: 0.68, 0.99). These findings suggest that psychosocial stress is associated with vaginal microbiota composition, inviting a more mechanistic exploration of the relationship between psychosocial stress and molecular-BV.

Biogenic Amines Increase the Odds of Bacterial Vaginosis and Affect the Growth of and Lactic Acid Production by Vaginal Lactobacillus spp.

Bacterial vaginosis (BV) is the most common vaginal disorder of reproductive-aged women, yet its etiology remains enigmatic. One clinical symptom of BV, malodor, is linked to the microbial production of biogenic amines (BA). Using targeted liquid chromatography mass spectrometry, we analyzed 149 longitudinally collected vaginal samples to determine the in vivo concentrations of the most common BAs and then assessed their relationship to BV and effect upon the growth kinetics of axenically cultured vaginal Lactobacillus species. Increases in cadaverine, putrescine, and tyramine were associated with greater odds of women transitioning from L. crispatus-dominated vaginal microbiota to microbiota that have a paucity of Lactobacillus spp. and from Nugent scores of 0 to 3 to Nugent scores of 7 to 10, consistent with BV. Exposure to putrescine lengthened the lag time and/or slowed the growth of all vaginal Lactobacillus spp. except L. jensenii 62G. L. iners AB107's lag time was lengthened by cadaverine but reduced in the presence of spermidine and spermine. The growth rate of L. crispatus VPI 3199 was slowed by cadaverine and tyramine, and strain-specific responses to spermine and spermidine were observed. BAs were associated with reduced production of d- and l-lactic acid by vaginal Lactobacillus spp., and this effect was independent of their effect upon Lactobacillus species growth. The exceptions were higher levels of d- and l-lactic acid by two strains of L. crispatus when grown in the presence of spermine. Results of this study provide evidence of a direct impact of common biogenic amines on vaginal Lactobacillus spp.IMPORTANCELactobacillus spp. are credited with providing the primary defense against gynecological conditions, including BV, most notably through the acidification of the vaginal microenvironment, which results from their production of lactic acid. The microbial production of BAs has been hypothesized to play a mechanistic role in diminishing Lactobacillus species-mediated protection, enabling the colonization and outgrowth of diverse anaerobic bacterial species associated with BV. Here, we demonstrate that in vivo increases in the most commonly observed BAs are associated with a loss of Lactobacillus spp. and the development of BV, measured by Nugent score. Further, we show that BAs formed by amino acid decarboxylase enzymes negatively affect the growth of type strains of the most common vaginal Lactobacillus spp. and separately alter their production of lactic acid. These results suggest that BAs destabilize vaginal Lactobacillus spp. and play an important and direct role in diminishing their protection of the vaginal microenvironment.

Determinants of the postprandial triglyceride response to a high-fat meal in healthy overweight and obese adults.

BACKGROUND: Dyslipidemia is a feature of impaired metabolic health in conjunction with impaired glucose metabolism and central obesity. However, the contribution of factors to postprandial lipemia in healthy but metabolically at-risk adults is not well understood. We investigated the collective contribution of several physiologic and lifestyle factors to postprandial triglyceride (TG) response to a high-fat meal in healthy, overweight and obese adults. METHODS: Overweight and obese adults (n = 35) underwent a high-fat meal challenge with blood sampled at fasting and hourly in the 4-hour postprandial period after a breakfast containing 50 g fat. Incremental area under the curve (iAUC) and postprandial magnitude for TG were calculated and data analyzed using a linear model with physiologic and lifestyle characteristics as explanatory variables. Model reduction was used to assess which explanatory variables contributed most to the postprandial TG response. RESULTS: TG responses to a high-fat meal were variable between individuals, with approximately 57 % of participants exceeded the nonfasting threshold for hypertriglyceridemia. Visceral adiposity was the strongest predictor of TG iAUC (ß = 0.53, p = 0.01), followed by aerobic exercise frequency (ß = 0.31, p = 0.05), insulin resistance based on HOMA-IR (ß = 0.30, p = 0.04), and relative exercise intensity at which substrate utilization crossover occurred (ß = 0.05, p = 0.04). For postprandial TG magnitude, visceral adiposity was a strong predictor (ß = 0.43, p < 0.001) followed by aerobic exercise frequency (ß = 0.23, p = 0.01), and exercise intensity for substrate utilization crossover (ß = 0.53, p = 0.01). CONCLUSIONS: Postprandial TG responses to a high-fat meal was partially explained by several physiologic and lifestyle characteristics, including visceral adiposity, insulin resistance, aerobic exercise frequency, and relative substrate utilization crossover during exercise. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04128839 , Registered 16 October 2019 - Retrospectively registered.

Investigating the relationship between vaginal microbiota and host genetics and their impact on immune response and farrowing traits in commercial gilts.

Our objectives were to evaluate the interaction between host genetics and vaginal microbiota and their relationships with antibody (Ab) response to porcine reproductive and respiratory syndrome virus (PRRSV) vaccination and farrowing performance in commercial gilts. The farrowing performance traits were number born alive, number weaning (NW), total number born, number born dead, stillborn, mummies and preweaning mortality (PWM). The vaginal microbiota was collected on days 4 (D4) and 52 (D52) after vaccination for PRRSV. Blood samples were collected on D52 for Ab measurement. Actinobacteria, Bacterioidetes, Firmicutes, Proteobacteria and Tenericutes were the most abundant Phyla identified in the vaginal microbiota. Heritability ranged from ~0 to 0.60 (Fusobacterium) on D4 and from ~0 to 0.63 (Terrisporobacter) on D52, with 43 operational taxonomic units (OTUs) presenting moderate to high heritability. One major QTL on chromosome 12 was identified for 5 OTUs (Clostridiales, Acinetobacter, Ruminococcaceae, Campylobacter and Anaerococcus), among other 19 QTL. The microbiability for Ab response to PRRSV vaccination was low for both days (<0.07). For farrowing performance, microbiability varied from <0.001 to 0.15 (NW on D4). For NW and PWM, the microbiability was greater than the heritability estimates. Actinobacillus, Streptococcus, Campylobacter, Anaerococcus, Mollicutes, Peptostreptococcus, Treponema and Fusobacterium showed different abundance between low and high Ab responders. Finally, canonical discriminant analyses revealed that vaginal microbiota was able to classify gilts in high and low Ab responders to PRRSV vaccination with a misclassification rate of <0.02. Although the microbiota explained limited variation in Ab response and farrowing performance traits, there is still potential to explore the use of vaginal microbiota to explain variation in traits such as NW and PWM. In addition, these results revealed that there is a partial control of host genetic over vaginal microbiota, suggesting a possibility for genetic selection on the vaginal microbiota.

Gut microbiome composition of wild western lowland gorillas is associated with individual age and sex factors.

OBJECTIVES: Environmental and ecological factors, such as geographic range, anthropogenic pressure, group identity, and feeding behavior are known to influence the gastrointestinal microbiomes of great apes. However, the influence of individual host traits such as age and sex, given specific dietary and social constraints, has been less studied. The objective of this investigation was to determine the associations between an individual's age and sex on the diversity and composition of the gut microbiome in wild western lowland gorillas. MATERIALS AND METHODS: Publicly available 16S rRNA data generated from fecal samples of different groups of Gorilla gorilla gorilla in the Central African Republic were downloaded and bioinformatically processed. The groups analyzed included habituated, partially habituated and unhabituated gorillas, sampled during low fruit (dry, n = 28) and high fruit (wet, n = 82) seasons. Microbial community analyses (alpha and beta diversity and analyses of discriminant taxa), in tandem with network-wide approaches, were used to (a) mine for specific age and sex based differences in gut bacterial community composition and to (b) asses for gut community modularity and bacterial taxa with potential functional roles, in the context of seasonal food variation, and social group affiliation. RESULTS: Both age and sex significantly influenced gut microbiome diversity and composition in wild western lowland gorillas. However, the largest differences were observed between infants and adults in habituated groups and between adults and immature gorillas within all groups, and across dry and wet seasons. Specifically, although adults always showed greater bacterial richness than infants and immature gorillas, network-wide analyses showed higher microbial community complexity and modularity in the infant gorilla gut. Sex-based microbiome differences were not evident among adults, being only detected among immature gorillas. CONCLUSIONS: The results presented point to a dynamic gut microbiome in Gorilla spp., associated with ontogeny and individual development. Of note, the gut microbiomes of breastfeeding infants seemed to reflect early exposure to complex, herbaceous vegetation. Whether increased compositional complexity of the infant gorilla gut microbiome is an adaptive response to an energy-limited diet and an underdeveloped gut needs to be further tested. Overall, age and sex based gut microbiome differences, as shown here, maybe mainly attributed to access to specific feeding sources, and social interactions between individuals within groups.

Impact of Cropping Systems, Soil Inoculum, and Plant Species Identity on Soil Bacterial Community Structure.

Farming practices affect the soil microbial community, which in turn impacts crop growth and crop-weed interactions. This study assessed the modification of soil bacterial community structure by organic or conventional cropping systems, weed species identity [Amaranthus retroflexus L. (redroot pigweed) or Avena fatua L. (wild oat)], and living or sterilized inoculum. Soil from eight paired USDA-certified organic and conventional farms in north-central Montana was used as living or autoclave-sterilized inoculant into steam-pasteurized potting soil, planted with Am. retroflexus or Av. fatua and grown for two consecutive 8-week periods to condition soil nutrients and biota. Subsequently, the V3-V4 regions of the microbial 16S rRNA gene were sequenced by Illumina MiSeq. Treatments clustered significantly, with living or sterilized inoculum being the strongest delineating factor, followed by organic or conventional cropping system, then individual farm. Living inoculum-treated soil had greater species richness and was more diverse than sterile inoculum-treated soil (observed OTUs, Chao, inverse Simpson, Shannon, P < 0.001) and had more discriminant taxa delineating groups (linear discriminant analysis). Living inoculum soil contained more Chloroflexi and Acidobacteria, while the sterile inoculum soil had more Bacteroidetes, Firmicutes, Gemmatimonadetes, and Verrucomicrobia. Organically farmed inoculum-treated soil had greater species richness, more diversity (observed OTUs, Chao, Shannon, P < 0.05), and more discriminant taxa than conventionally farmed inoculum-treated soil. Cyanobacteria were higher in pots growing Am. retroflexus, regardless of inoculum type, for three of the four organic farms. Results highlight the potential of cropping systems and species identity to modify soil bacterial communities, subsequently modifying plant growth and crop-weed competition.

Unraveling the pectinolytic function of Bacteroides xylanisolvens using a RNA-seq approach and mutagenesis.

BACKGROUND: Diet and particularly dietary fibres have an impact on the gut microbiome and play an important role in human health and disease. Pectin is a highly consumed dietary fibre found in fruits and vegetables and is also a widely used additive in the food industry. Yet there is no information on the effect of pectin on the human gut microbiome. Likewise, little is known on gut pectinolytic bacteria and their enzyme systems. This study was undertaken to investigate the mechanisms of pectin degradation by the prominent human gut symbiont Bacteroides xylanisolvens. RESULTS: Transcriptomic analyses of B. xylanisolvens XB1A grown on citrus and apple pectins at mid- and late-log phases highlighted six polysaccharide utilization loci (PUL) that were overexpressed on pectin relative to glucose. The PUL numbers used in this report are those given by Terrapon et al. (Bioinformatics 31(5):647-55, 2015) and found in the PUL database: http://www.cazy.org/PULDB/. Based on their CAZyme composition, we propose that PUL 49 and 50, the most overexpressed PULs on both pectins and at both growth phases, are involved in homogalacturonan (HG) and type I rhamnogalacturonan (RGI) degradation, respectively. PUL 13 and PUL 2 could be involved in the degradation of arabinose-containing side chains and of type II rhamnogalacturonan (RGII), respectively. Considering that HG is the most abundant moiety (>70%) within pectin, the importance of PUL 49 was further investigated by insertion mutagenesis into the susC-like gene. The insertion blocked transcription of the susC-like and the two downstream genes (susD-like/FnIII). The mutant showed strong growth reduction, thus confirming that PUL 49 plays a major role in pectin degradation. CONCLUSION: This study shows the existence of six PULs devoted to pectin degradation by B. xylanisolvens, one of them being particularly important in this function. Hence, this species deploys a very complex enzymatic machinery that probably reflects the structural complexity of pectin. Our findings also highlight the metabolic plasticity of B. xylanisolvens towards dietary fibres that contributes to its competitive fitness within the human gut ecosystem. Wider functional and ecological studies are needed to understand how dietary fibers and especially plant cell wall polysaccharides drive the composition and metabolism of the fibrolytic and non-fibrolytic community within the gut microbial ecosystem.

Xylan degradation by the human gut Bacteroides xylanisolvens XB1A(T) involves two distinct gene clusters that are linked at the transcriptional level.

BACKGROUND: Plant cell wall (PCW) polysaccharides and especially xylans constitute an important part of human diet. Xylans are not degraded by human digestive enzymes in the upper digestive tract and therefore reach the colon where they are subjected to extensive degradation by some members of the symbiotic microbiota. Xylanolytic bacteria are the first degraders of these complex polysaccharides and they release breakdown products that can have beneficial effects on human health. In order to understand better how these bacteria metabolize xylans in the colon, this study was undertaken to investigate xylan breakdown by the prominent human gut symbiont Bacteroides xylanisolvens XB1A(T). RESULTS: Transcriptomic analyses of B. xylanisolvens XB1A(T) grown on insoluble oat-spelt xylan (OSX) at mid- and late-log phases highlighted genes in a polysaccharide utilization locus (PUL), hereafter called PUL 43, and genes in a fragmentary remnant of another PUL, hereafter referred to as rPUL 70, which were highly overexpressed on OSX relative to glucose. Proteomic analyses supported the up-regulation of several genes belonging to PUL 43 and showed the important over-production of a CBM4-containing GH10 endo-xylanase. We also show that PUL 43 is organized in two operons and that the knockout of the PUL 43 sensor/regulator HTCS gene blocked the growth of the mutant on insoluble OSX and soluble wheat arabinoxylan (WAX). The mutation not only repressed gene expression in the PUL 43 operons but also repressed gene expression in rPUL 70. CONCLUSION: This study shows that xylan degradation by B. xylanisolvens XB1A(T) is orchestrated by one PUL and one PUL remnant that are linked at the transcriptional level. Coupled to studies on other xylanolytic Bacteroides species, our data emphasize the importance of one peculiar CBM4-containing GH10 endo-xylanase in xylan breakdown and that this modular enzyme may be used as a functional marker of xylan degradation in the human gut. Our results also suggest that B. xylanisolvens XB1A(T) has specialized in the degradation of xylans of low complexity. This functional feature may provide a niche to all xylanolytic bacteria harboring similar PULs. Further functional and ecological studies on fibrolytic Bacteroides species are needed to better understand their role in dietary fiber degradation and their impact on intestinal health.

Effect of Antibiotic Treatment on the Gastrointestinal Microbiome of Free-Ranging Western Lowland Gorillas (Gorilla g. gorilla).

The mammalian gastrointestinal (GI) microbiome, which plays indispensable roles in host nutrition and health, is affected by numerous intrinsic and extrinsic factors. Among them, antibiotic (ATB) treatment is reported to have a significant effect on GI microbiome composition in humans and other animals. However, the impact of ATBs on the GI microbiome of free-ranging or even captive great apes remains poorly characterized. Here, we investigated the effect of cephalosporin treatment (delivered by intramuscular dart injection during a serious respiratory outbreak) on the GI microbiome of a wild habituated group of western lowland gorillas (Gorilla gorilla gorilla) in the Dzanga Sangha Protected Areas, Central African Republic. We examined 36 fecal samples from eight individuals, including samples before and after ATB treatment, and characterized the GI microbiome composition using Illumina-MiSeq sequencing of the bacterial 16S rRNA gene. The GI microbial profiles of samples from the same individuals before and after ATB administration indicate that the ATB treatment impacts GI microbiome stability and the relative abundance of particular bacterial taxa within the colonic ecosystem of wild gorillas. We observed a statistically significant increase in Firmicutes and a decrease in Bacteroidetes levels after ATB treatment. We found disruption of the fibrolytic community linked with a decrease of Ruminoccocus levels as a result of ATB treatment. Nevertheless, the nature of the changes observed after ATB treatment differs among gorillas and thus is dependent on the individual host. This study has important implications for ecology, management, and conservation of wild primates.

Gut microbiome composition and metabolomic profiles of wild western lowland gorillas (Gorilla gorilla gorilla) reflect host ecology.

The metabolic activities of gut microbes significantly influence host physiology; thus, characterizing the forces that modulate this micro-ecosystem is key to understanding mammalian biology and fitness. To investigate the gut microbiome of wild primates and determine how these microbial communities respond to the host's external environment, we characterized faecal bacterial communities and, for the first time, gut metabolomes of four wild lowland gorilla groups in the Dzanga-Sangha Protected Areas, Central African Republic. Results show that geographical range may be an important modulator of the gut microbiomes and metabolomes of these gorilla groups. Distinctions seemed to relate to feeding behaviour, implying energy harvest through increased fruit consumption or fermentation of highly fibrous foods. These observations were supported by differential abundance of metabolites and bacterial taxa associated with the metabolism of cellulose, phenolics, organic acids, simple sugars, lipids and sterols between gorillas occupying different geographical ranges. Additionally, the gut microbiomes of a gorilla group under increased anthropogenic pressure could always be distinguished from that of all other groups. By characterizing the interplay between environment, behaviour, diet and symbiotic gut microbes, we present an alternative perspective on primate ecology and on the forces that shape the gut microbiomes of wild primates from an evolutionary context.

The gut microbiota appears to compensate for seasonal diet variation in the wild black howler monkey (Alouatta pigra).

For most mammals, including nonhuman primates, diet composition varies temporally in response to differences in food availability. Because diet influences gut microbiota composition, it is likely that the gut microbiota of wild mammals varies in response to seasonal changes in feeding patterns. Such variation may affect host digestive efficiency and, ultimately, host nutrition. In this study, we investigate the temporal variation in diet and gut microbiota composition and function in two groups (N = 13 individuals) of wild Mexican black howler monkeys (Alouatta pigra) over a 10-month period in Palenque National Park, Mexico. Temporal changes in the relative abundances of individual bacterial taxa were strongly correlated with changes in host diet. For example, the relative abundance of Ruminococcaceae was highest during periods when energy intake was lowest, and the relative abundance of Butyricicoccus was highest when young leaves and unripe fruit accounted for 68 % of the diet. Additionally, the howlers exhibited increased microbial production of energy during periods of reduced energy intake from food sources. Because we observed few changes in howler activity and ranging patterns during the course of our study, we propose that shifts in the composition and activity of the gut microbiota provided additional energy and nutrients to compensate for changes in diet. Energy and nutrient production by the gut microbiota appears to provide an effective buffer against seasonal fluctuations in energy and nutrient intake for these primates and is likely to have a similar function in other mammal species.

The role of gut microbes in satisfying the nutritional demands of adult and juvenile wild, black howler monkeys (Alouatta pigra).

In all mammals, growth, development, pregnancy, and lactation increase nutritional demands. Although primate field studies tend to focus on shifts in activity and diet as mechanisms to compensate for these demands, differences in digestive efficiency also are likely to be important. Because the gut microbiota can impact host digestive efficiency, we examined differences in activity budget, diet, and the gut microbial community among adult male (N = 4), adult female (N = 4), and juvenile (N = 5) wild black howler monkeys (Alouatta pigra) across a ten-month period in Palenque National Park, Mexico to determine how adult females and juveniles compensate for increased nutritional demands. Results indicate that adult females and juveniles consumed more protein and energy than adult males. Adult males, adult females, and juveniles also possessed distinct gut microbial communities, unrelated to diet. Juveniles exhibited a gut microbiota characterized by bacteria from the phylum Firmicutes, such as Roseburia and Ruminococcus, and demonstrated high fecal volatile fatty acid content, suggesting increased microbial contributions to host energy balances. Adult females possessed a higher Firmicutes to Bacteroidetes ratio, also suggesting increased energy production, and their gut microbiota was characterized by Lactococcus, which has been associated with folate biosynthesis. On the basis of these patterns, it appears that the gut microbiota differentially contributes to howler monkey nutrition during reproduction and growth. Determining the nutritional and energetic importance of shifts in activity, diet, and the gut microbiota in other nonhuman primate taxa, as well as humans, will transform our understanding of these life history processes and the role of host-microbe relationships in primate evolution.

The primate vaginal microbiome: comparative context and implications for human health and disease.

The primate body hosts trillions of microbes. Interactions between primate hosts and these microbes profoundly affect primate physiology, reproduction, health, survival, and ultimately, evolution. It is increasingly clear that primate health cannot be understood fully without knowledge of host-microbial interactions. Our goals here are to review what is known about microbiomes of the female reproductive tract and to explore several factors that influence variation within individuals, as well as within and between primate species. Much of our knowledge of microbial variation derives from studies of humans, and from microbes located in nonreproductive regions (e.g., the gut). We review work suggesting that the vaginal microbiota affects female health, fecundity, and pregnancy outcomes, demonstrating the selective potential for these agents. We explore the factors that correlate with microbial variation within species. Initial colonization by microbes depends on the manner of birth; most microbial variation is structured by estrogen levels that change with age (i.e., at puberty and menopause) and through the menstrual cycle. Microbial communities vary by location within the vagina and can depend on the sampling methods used (e.g., swab, lavage, or pap smear). Interindividual differences also exist, and while this variation is not completely understood, evidence points more to differences in estrogen levels, rather than differences in external physical environment. When comparing across species, reproductive-age humans show distinct microbial communities, generally dominated by Lactobacillus, unlike other primates. We develop evolutionary hypotheses to explain the marked differences in microbial communities. While much remains to be done to test these hypotheses, we argue that the ample variation in primate mating and reproductive behavior offers excellent opportunities to evaluate host-microbe coevolution and adaptation.

Metabolic impact of polyphenol-rich aronia fruit juice mediated by inflammation status of gut microbiome donors in humanized mouse model.

Background: The Aronia melanocarpa fruit is emerging as a health food owing to its high polyphenolic content and associated antioxidant activity. Antioxidant-rich foods, such as Aronia fruit, may counter inflammatory stimuli and positively modulate the gut microbiome. However, a comprehensive study characterizing the impact of Aronia fruit supplementation has not been completed. Therefore, we completed analyses measuring the metabolic, microbial, and inflammatory effects of a diet supplemented with Aronia fruit juice. Method: Humanized mice were generated by colonizing gnotobiotic mice with microbiomes from human donors presenting disparate inflammation levels. Blood and fecal samples were collected throughout the course of an 8-week dietary intervention with either Aronia juice or a carbohydrate-matched beverage alone (2 weeks) or in combination with a high-fat diet to induce inflammation (6 weeks). Samples were analyzed using 16S rRNA gene sequencing (stool) and liquid chromatography-mass spectrometry (serum). Results: We demonstrated transfer of microbiome composition and diversity and metabolic characteristics from humans with low and high inflammation levels to second-generation humanized mice. Aronia supplementation provided robust protection against high-fat diet induced metabolic and microbiome changes that were dependent in part on microbiome donor. Aronia induced increases in bacteria of the Eggerthellaceae genus (7-fold) which aligns with its known ability to metabolize (poly)phenols and in phosphatidylcholine metabolites which are consistent with improved gut barrier function. The gut microbiome from a low inflammation phenotype donor provided protection against high-fat diet induced loss of microbiome ß-diversity and global metabolomic shifts compared to that from the high inflammation donor. Conclusion: These metabolic changes elucidate pathway-specific drivers of reduced inflammation stemming from both Aronia and the gut microbiota.

Phage-bacteria relationships and CRISPR elements revealed by a metagenomic survey of the rumen microbiome.

Viruses are the most abundant biological entities on the planet and play an important role in balancing microbes within an ecosystem and facilitating horizontal gene transfer. Although bacteriophages are abundant in rumen environments, little is known about the types of viruses present or their interaction with the rumen microbiome. We undertook random pyrosequencing of virus-enriched metagenomes (viromes) isolated from bovine rumen fluid and analysed the resulting data using comparative metagenomics. A high level of diversity was observed with up to 28,000 different viral genotypes obtained from each environment. The majority (~78%) of sequences did not match any previously described virus. Prophages outnumbered lytic phages approximately 2:1 with the most abundant bacteriophage and prophage types being associated with members of the dominant rumen phyla (Firmicutes and Proteobacteria). Metabolic profiling based on SEED subsystems revealed an enrichment of sequences with putative functional roles in DNA and protein metabolism, but a surprisingly low proportion of sequences assigned to carbohydrate and amino acid metabolism. We expanded our analysis to include previously described metagenomic data and 14 reference genomes. Clustered regularly interspaced short palindromic repeats (CRISPR) were detected in most of the microbial genomes, suggesting previous interactions between viral and microbial communities.

Do gastrointestinal microbiomes play a role in bats' unique viral hosting capacity?

Bats are reservoirs for zoonotic viruses, which they tolerate without experiencing disease. Research focused on deciphering mechanisms of virus tolerance in bats has rarely considered the influence of their gastrointestinal tract (GIT) microbiome. In mammals, GIT microbiomes influence infections through their effect on host physiology, immunity, nutrition, and behavior. Bat GIT microbiomes more closely resemble the Proteobacteria-dominated GIT microbiomes of birds than those of other mammals. As an adaptation to flight, bats have rapid GIT transit times which may reduce the stability of their microbiome, constrain nutrient uptake, and affect pathogen exposure and evolution of tolerance mechanisms. Experimental and longitudinal studies are needed to understand the function of bats' GIT microbiomes and their role in modulating viral infection dynamics.