Frontiers in microbiomes最新文献

A healthy vaginal microbiome (VMB) is dominated by Lactobacillus spp. and provides the first line of defense against invading pathogens. Vaginal dysbiosis, characterized by the loss of Lactobacillus dominance and increase of microbial diversity, has been linked to an increased risk of adverse genital tract diseases, including bacterial vaginosis, aerobic vaginitis, vulvovaginal candidiasis, sexually transmitted infections, and pregnancy complications such as preterm birth. Currently, antibiotics and antifungals are recommended first-line treatments with high cure rates, but they also can lead to high recurrence and resistance development. As an alternative, lactobacilli have been utilized to restore the vaginal microbiota. In this review article, we discuss vaginal dysbiosis in various gynecological infections and potential interventions based on Live Biotherapeutic Products (LBPs) with a focus on those that use intravaginal treatment modalities to modulate the VMB. Based on these, we provide insights on key factors to consider in designing phenotypic and genotypic screens for selecting bacterial strains for use as vaginally administered microbiome-directed therapeutics. Lastly, to highlight current progress within this field, we provide an overview of LBPs currently being developed with published clinical trial completion for recurrent BV, VVC, and UTI. We also discuss regulatory challenges in the drug development process to harmonize future research efforts in VMB therapy.

The average American spends 93% of their time in built environments, almost 70% of that is in their place of residence. Human health and well-being are intrinsically tied to the quality of our personal environments and the microbiomes that populate them. Conversely, the built environment microbiome is seeded, formed, and re-shaped by occupant behavior, cleaning, personal hygiene and food choices, as well as geographic location and variability in infrastructure. Here, we focus on the presence of viruses in household biofilms, specifically in showerheads and on toothbrushes. Bacteriophage, viruses that infect bacteria with high host specificity, have been shown to drive microbial community structure and function through host infection and horizontal gene transfer in environmental systems. Due to the dynamic environment, with extreme temperature changes, periods of wetting/drying and exposure to hygiene/cleaning products, in addition to low biomass and transient nature of indoor microbiomes, we hypothesize that phage host infection in these unique built environments are different from environmental biofilm interactions. We approach the hypothesis using metagenomics, querying 34 toothbrush and 92 showerhead metagenomes. Representative of biofilms in the built environment, these interfaces demonstrate distinct levels of occupant interaction. We identified 22 complete, 232 high quality, and 362 medium quality viral OTUs. Viral community richness correlated with bacterial richness but not Shannon or Simpson indices. Of quality viral OTUs with sufficient coverage (614), 532 were connected with 32 bacterial families, of which only Sphingomonadaceae, Burkholderiaceae, and Caulobacteraceae are found in both toothbrushes and showerheads. Low average nucleotide identity to reference sequences and a high proportion of open reading frames annotated as hypothetical or unknown indicate that these environments harbor many novel and uncharacterized phage. The results of this study reveal the paucity of information available on bacteriophage in indoor environments and indicate a need for more virus-focused methods for DNA extraction and specific sequencing aimed at understanding viral impact on the microbiome in the built environment.

The cattle production system focuses on maintaining an animal-based food supply with a lower number of cattle. However, the fecundity of dairy cows has declined worldwide. The reproductive tract microbiome is one of the important factors which can influence bovine fecundity. Therefore, reproductive tract microbiomes have been explored during the estrus cycle, artificial insemination, gestation, and postpartum to establish a link between the micro-communities and reproductive performance. These investigations suggested that microbial dysbiosis in the reproductive tract may be associated with declined fertility. However, there is a scarcity of comprehensive investigations to understand microbial diversity, abundance, shift, and host-microbiome interplay for bovine infertility cases such as repeat breeding syndrome (RBS). This review summarizes the occurrence and persistence of microbial taxa to gain a better understanding of reproductive performance and its implications. Further, we also discuss the possibilities of microbiome manipulation strategies to enhance bovine fecundity.

Introduction: Pathogen introduction and transmission at the farm, regional, or national level are associated with reduced animal welfare and negative impacts on herd economics. Ongoing infectious disease surveillance, active or passive, is therefore of high importance. For optimal resolution, each pig is sampled individually, for example by collecting blood or nasal swabs. In recent years, oral fluids have become very useful for population surveillance at the pen level. Another alternative is sampling the air to capture pathogens circulating across the entire barn via bioaerosols.

Objective: This study aimed to examine the potential utility of bioaerosol metagenomics for pathogen detection on pig farms.

Methods: Bioaerosols via automated air sampler, and oral fluid via pen-based ropes, were collected from each of two Scottish indoor pig farms. All samples were subjected to conventional routine bacterial isolation. Total genomic nucleic acids were extracted for PCR screening for three pig DNA viruses, three bacterial Mycoplasma species and an RNA virus. Illumina shotgun metagenomic sequencing was also conducted.

Results: Oral fluids contained more DNA compared to bioaerosol samples. DNA integrity exhibited limited impact on PCR or sequence yield. While Streptococcus suis could be cultured from a single oral fluid sample, reads mapped to S. suis were detectable in all metagenomic samples. Other bacterial pig pathogens, including Mycoplasma hyorhinis, M. hyopneumoniae and M. hyosynoviae, were detected in oral fluid and aerosols by PCR and metagenomics. One of the two farms was PRRSV positive, and the virus was detectable via PCR in oral fluids but not in bioaerosols. Antimicrobial resistance (AMR) gene profiles had less variation between bioaerosols and oral fluids. Some identified AMR genes had strikingly similar abundance overall.

Conclusion: Overall, these findings indicate that there is potential utility of bioaerosol metagenomics for pathogen surveillance on pig farms; however, more research is needed for technical and cost optimization to allow for routine pathogen detection on livestock farms.

The use of potentially beneficial microorganisms in agriculture (microbial inoculants) has rapidly accelerated in recent years. For microbial inoculants to be effective as agricultural tools, these organisms must be able to survive and persist in novel environments while not destabilizing the resident community or spilling over into adjacent natural ecosystems. Despite the importance of propagule pressure to species introductions, few tools exist in microbial ecology to predict the outcomes of agricultural microbial introductions. Here, we adapt a macroecological propagule pressure model to a microbial scale and present an experimental approach for testing the role of propagule pressure in microbial inoculant introductions. We experimentally determined the risk-release relationship for an IAA-expressing Pseudomonas simiae inoculant in a model monocot system. We then used this relationship to simulate establishment outcomes under a range of application frequencies (propagule number) and inoculant concentrations (propagule size). Our simulations show that repeated inoculant applications may increase establishment, even when increased inoculant concentration does not alter establishment probabilities. Applying ecological modeling approaches like those presented here to microbial inoculants may aid their sustainable use and provide a monitoring tool for microbial inoculants.

Introduction: Liquiritigenin (LQ), a natural flavonoid found in traditional Chinese medicine and often administered orally, holds potential to affect both the gut and its microbiota, that potentially mediating or influencing its biological and pharmacological effects. However, the effects of LQ on gut microbiota composition and intestinal function remain poorly understood. In this study, we aimed to explore the impact of LQ on gut microbiota and gene expression in both intestinal and extraintestinal tissues.

Methods: We orally inoculated six-week-old SPF C57BL/6 mice with either LQ (a concentration of 4 mg/ml diluted in dimethylsulfoxide, (DMSO)) or DMSO, and administered daily for a duration of 2 weeks. At the end of the experimental period, all mice were euthanized. Fresh fecal samples, as well as samples from the intestine, lung, and liver, were collected for subsequent microbiota analysis, RNA-seq, or histochemical and immunohistochemical (IHC) staining.

Results: Findings show that LQ alters gut microbiota composition, enhancing microbial correlations in the colon but causing some dysbiosis, evidenced by increased pathobionts, decreased beneficial bifidobacteria, and reduced microbiota diversity. Gene expression analysis reveals LQ upregulates mucosal immune response genes and antiinfection genes in both the intestine and lung, with histology confirming increased Paneth cells and antimicrobial peptides in the intestine. Additionally, LQ affects tissue-specific gene expression, triggering hypersensitivity genes in the colon, downregulating metabolic genes in the small intestine, and reducing cell motility and adhesion genes in the lung.

Discussion: These results suggest LQ's potential to modulate common mucosal immunity but also highlight possible risks of gut dysbiosis and hypersensitivity, particularly in vulnerable individuals. Our study, while informative about the effects of LQ on gut health, lacks direct evidence on whether changes in gut microbiota and gene expression caused by LQ impact inflammatory diseases or are causally linked. Future research should investigate this through fecal microbiota transplantation to explore the causal relationships and LQ's potential effects on immune responses and disease outcomes in relevant models.

The symbiotic relationship between the gut microbiome and the human body is a concept that has grown in popularity in recent years. Bacteriophages (phages) are components of the gut microbiota and their imbalance plays a role in the pathogenesis of numerous intestinal disorders. Meanwhile, as a new antimicrobial agent, phage therapy (PT) offers unique advantages when compared with antibiotics and brings a new dawn for treatment of multidrug-resistant bacteria in intestinal and extraintestinal disorders. In this review, we provide a brief introduction to the characterization of phages, particularly focusing on newly discovered phages. Additionally, we outline the involvement of gut phages in disease pathogenesis and discuss the status and challenges of utilizing phages as therapeutic targets for treatment of enteric infection.

Introduction: Sequelae from traumatic brain injuries (TBIs) and post-traumatic stress disorder (PTSD) are major career-limiting factors for combat soldiers. Overlap between TBI and PTSD symptoms alongside other common comorbidities complicate the diagnosis and treatment. Systems-level and high-throughput approaches are key in understanding the underlying biomolecular mechanisms and differentiating these conditions.

Methods: The present study identifies dietary factors and proposes mechanisms behind psychological stress and TBI, using established preclinical animal models and a multi-omics approach. Here, we used microbiome characterizations of rats exposed to simulations of blast-induced TBI and underwater trauma (UWT)-induced psychological stress. We further studied the effect of dietary omega-6 versus omega-3 polyunsaturated fatty acid (n-6, n-3 PUFA) enrichment on the insult responses. The use of excess n-6 PUFA was chosen due to its high prevalence in the Western diet and pro-inflammatory nature. Prior to TBI or UWT, animals were maintained for 6 weeks and continued thereafter on either a standard diet or two customized chows imbalanced and diminished in omega-3 content. Corresponding shams were carried out for all groups. Fecal bacterial microbiome populations were assessed using 16S rRNA gene sequencing.

Results: Physiologic outcome modeling identified that dietary status affected post-TBI lactate dehydrogenase (LDH) and triglyceride levels, with n-3 PUFA having a large attenuating influence. The UWT model showed similar trends, with diet significantly altering LDH, terminal corticosterone (14 days post-exposure), and a fear behavior susceptibility. Fecal microbiome alpha diversity was significantly reduced by high levels of n-3 PUFA. Likewise, beta diversity of the microbiome was significantly affected by both diet and time but not exposure to TBI or UWT. Compositionally, temporal effects on the microbiome were more likely to be observed with the diets. The most affected features fell within the Proteobacteria phyla, in which n-3 PUFA enrichment significantly reduced Alphaproteobacteria in the TBI model and increased Gammaproteobacteria in the UWT group.

Discussion: All these observations can influence the vulnerability or resilience of the warfighter to blast-induced TBI and acute psychological stress. The microbiome mechanisms facilitate and provide a knowledge-driven unbiased panel of signatures to discriminate between the two insults and is an essential tool for designing precise care management.

[This corrects the article DOI: 10.3389/frmbi.2024.1359580.].

Metagenomic studies have revolutionized the study of novel phages. However these studies trade depth of coverage for breadth. We show that the targeted sequencing of a small region of a phage terminase family can provide sufficient sequence diversity to serve as an individual-specific barcode or a "phageprint'', defined as the relative abundance profile of the variants within a terminase family. By collecting ~700 oral samples from ~100 individuals living on multiple continents, we found a consistent trend wherein each individual harbors one or two dominant variants that coexist with numerous low-abundance variants. By tracking phageprints over the span of a month across ten individuals, we observed that phageprints were generally stable, and found instances of concordant temporal fluctuations of variants shared between partners. To quantify these patterns further, we built machine learning models that, with high precision and recall, distinguished individuals even when we eliminated the most abundant variants and further downsampled phageprints to 2% of the remaining variants. Except between partners, phageprints are dissimilar between individuals, and neither country-of-residence, genetics, diet nor cohabitation seem to play a role in the relatedness of phageprints across individuals. By sampling from six different oral sites, we were able to study the impact of millimeters to a few centimeters of separation on an individual's phageprint and found that such limited spatial separation results in site-specific phageprints.