Human Microbiome Research Articles

12468 Loss Of Enterococcus And Faecalibacterium Associate With Polycystic Ovary Syndrome And Hirsutism In A Sample Of Hispanic Patients

Abstract Disclosure: L.A. Gonzalez-Rodriguez: Research Investigator; Self; Eli Lilly & Company. C.M. Casas Loyola: None. C.I. Martinez-Hernandez: None. L. El Musa Penna: None. J. Romaguera: None. F. Godoy-Vitorino: None. Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age. It is characterized by symptoms such as irregular menstrual periods, excess androgen levels and polycystic ovaries. Women with PCOS often display insulin resistance independent of fat and have been associated with an increased risk of diabetes mellitus, cardiovascular disease, and mood disorders. The gut microbiota, the community of microbes living in the human gastrointestinal tract, plays a crucial role in human health and has been implicated in various diseases, including metabolic and inflammatory conditions. We aimed to characterize the gut microbiota in a sample of Hispanic women living in Puerto Rico (n=50). Of these 38 had confirmed PCOS as per Rotterdam criteria and 12 were controls. A stool sample was collected for genomic DNA extractions followed by amplification and sequencing of 16S rRNA genes (V4 region) with Illumina MiSEQ. Data analyses were performed with standard pipelines with variables sample group (PCOS vs Controls), insulin resistance assessed using HOMA-IR and hirsutism status according to modified-Ferriman Gallwey (mFG) score and controlled for age and other clinical variables. Despite there were no changes in alpha or beta diversity among the microbiota of these groups, composition was significantly different. Women with PCOS had significantly lower levels of Enterococcus species as well as Hungatella, taxa that are part of a physiologically normal gut flora. Enterococcus species contribute to the balance of the microbial community and play roles in the metabolism and immune function and are very resilient. Hungatella species are a known source of catabolic enzymes that degrade glycosaminoglycans which are important in tissue repair. These dominant taxa in controls was substituted by other taxa in PCOS. Women with prominent hirsutism had significantly lower levels of Faecalibacterium while those with insulin resistance had increased levels of Clostridium. We found that higher levels Clostridium, and lower levels of protective anti-inflammatory taxa such as Faecalibacterium or Enterococci, which are important for gut health and metabolic regulation, are linked to this metabolic disturbance. Even though this is a preliminary report, it opens potential therapeutic strategies, such as the use probiotics, and dietary modifications to modulate the gut microbiome and improve PCOS outcomes. Presentation: 6/1/2024

12468 Loss Of Enterococcus And Faecalibacterium Associate With Polycystic Ovary Syndrome And Hirsutism In A Sample Of Hispanic Patients

Abstract Disclosure: L.A. Gonzalez-Rodriguez: Research Investigator; Self; Eli Lilly & Company. C.M. Casas Loyola: None. C.I. Martinez-Hernandez: None. L. El Musa Penna: None. J. Romaguera: None. F. Godoy-Vitorino: None. Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age. It is characterized by symptoms such as irregular menstrual periods, excess androgen levels and polycystic ovaries. Women with PCOS often display insulin resistance independent of fat and have been associated with an increased risk of diabetes mellitus, cardiovascular disease, and mood disorders. The gut microbiota, the community of microbes living in the human gastrointestinal tract, plays a crucial role in human health and has been implicated in various diseases, including metabolic and inflammatory conditions. We aimed to characterize the gut microbiota in a sample of Hispanic women living in Puerto Rico (n=50). Of these 38 had confirmed PCOS as per Rotterdam criteria and 12 were controls. A stool sample was collected for genomic DNA extractions followed by amplification and sequencing of 16S rRNA genes (V4 region) with Illumina MiSEQ. Data analyses were performed with standard pipelines with variables sample group (PCOS vs Controls), insulin resistance assessed using HOMA-IR and hirsutism status according to modified-Ferriman Gallwey (mFG) score and controlled for age and other clinical variables. Despite there were no changes in alpha or beta diversity among the microbiota of these groups, composition was significantly different. Women with PCOS had significantly lower levels of Enterococcus species as well as Hungatella, taxa that are part of a physiologically normal gut flora. Enterococcus species contribute to the balance of the microbial community and play roles in the metabolism and immune function and are very resilient. Hungatella species are a known source of catabolic enzymes that degrade glycosaminoglycans which are important in tissue repair. These dominant taxa in controls was substituted by other taxa in PCOS. Women with prominent hirsutism had significantly lower levels of Faecalibacterium while those with insulin resistance had increased levels of Clostridium. We found that higher levels Clostridium, and lower levels of protective anti-inflammatory taxa such as Faecalibacterium or Enterococci, which are important for gut health and metabolic regulation, are linked to this metabolic disturbance. Even though this is a preliminary report, it opens potential therapeutic strategies, such as the use probiotics, and dietary modifications to modulate the gut microbiome and improve PCOS outcomes. Presentation: 6/1/2024

7013 An Inpatient Perspective: Hyperprolactinemia and Granulomatous Mastitis

Abstract Disclosure: A. Le: None. J. Wade: None. K. Martz: None. D. Girgis: None. M. Shahlapour: None. M.H. Horani: None. Introduction: Mastitis is a highly prevalent condition impacting thousands of women every year. Most commonly associated with lactation, mastitis is estimated to impact 2-20% of lactating women particularly in the first 4-6 weeks of breastfeeding (Wilson et al., 2020). The majority of cases are associated with bacterial infection with Staphylococcus aureus precipitated by nipple trauma and hyperlactation in the setting of genetic predispositions and disturbances to the human milk microbiota (Fernández et al., 2020). In rare cases, mastitis is seen outside of the context of lactation. One cause of non-lactational mastitis is idiopathic granulomatous mastitis (IGM). The pathogenesis of IGM is poorly understood, but there has been a rare association between IGM and hyperprolactinemia reported in the literature (Nikolaev et al., 2016). Case Presentation: In January 2022, A 20 year old female with past medical history of type 2 diabetes mellitus and hypertension, initially presented to the emergency department with complaints of headache. Patient’s history is notable for two years of amenorrhea and periodic nipple discharge. MRI scan of the head revealed a 1.6 cm pituitary macroadenoma which correlated with a markedly elevated prolactin level at 533.3. She was discharged with a prescription for Cabergoline 0.5 mg BID. In July 2022, the patient presented to the ED complaining of severe left breast pain with associated discharge for 4 days. She admitted to being non-adherent to Cabergoline treatment since April 2022 due to lack of endocrine follow-up. CT of the breast at that time showed a 3.8 cm subareolar abscess. Aspiration of the abscess revealed non-purulent fluid and cultures of the aspirate were negative. In February 2023, patient presented for right breast pain with a similar workup to previous hospitalization. MRI of the brain revealed a 1.6 cm sellar mass is unchanged since January 2022. Prolactin level was elevated at 652.4. Patient stated she has been off Cabergoline for the prior 5 months. She was subsequently seen for right and left mastitis 3 times over the next 12 months. Upon endocrine consultation, the patient was counseled on the importance of Cabergoline treatment in regression of future mastitis episodes, and the patient has subsequently not returned to our service. Conclusion: This case demonstrates the rare association between prolactin secreting pituitary adenomas and granulomatous mastitis that clinicians need to consider in order to avert delays in treatment and unnecessary hospitalizations. Specifically, when working up a patient with a history of IGM and prolactinemia, it is imperative to monitor prolactin levels periodically over an extended course of time with appropriate MRI imaging of the pituitary gland to assess for regression of prolactinoma and episodes of IGM. Presentation: 6/1/2024

Chronic Exposure to Petroleum-Derived Hydrocarbons Alters Human Skin Microbiome and Metabolome Profiles: A Pilot Study.

Petroleum-derived substances, like industrial oils and grease, are ubiquitous in our daily lives. Comprised of petroleum hydrocarbons (PH), these substances can come into contact with our skin, potentially causing molecular disruptions and contributing to the development of chronic disease. In this pilot study, we employed mass spectrometry-based untargeted metabolomics and 16S rRNA gene sequencing analyses to explore these effects. Superficial skin samples were collected from subjects with and without chronic dermal exposure to PH at two anatomical sites: the fingers (referred to as the hand) and arms (serving as an intersubject variability control). Exposed hands exhibited higher bacterial diversity (Shannon and Simpson indices) and an enrichment of oil-degrading bacteria (ODB), including Dietzia, Paracoccus, and Kocuria. Functional prediction suggested enriched pathways associated with PH degradation in exposed hands vs non-exposed hands, while no differences were observed when comparing the arms. Furthermore, carboxylic acids, glycerophospholipids, organooxygen compounds, phenol ethers, among others, were found to be more abundant in exposed hands. We observed positive correlations among multiple ODB and xenobiotics, suggesting a chemical remodeling of the skin favorable for ODB thriving. Overall, our study offers insights into the complex dysregulation of bacterial communities and the chemical milieu induced by chronic dermal exposure to PH.

Tailoring the natural rare sugars D-tagatose and L-sorbose to produce novel functional carbohydrates

This multidisciplinary study details the biosynthesis of novel non-digestible oligosaccharides derived from rare sugars, achieved through transfructosylation of D-tagatose and L-sorbose by levansucrase from Bacillus subtilis CECT 39 (SacB). The characterization of these carbohydrates using NMR and molecular docking was instrumental in elucidating the catalytic mechanism and substrate preference of SacB. Tagatose-based oligosaccharides were higher in abundance than L-sorbose-based oligosaccharides, with the most representative structures being: β-D-Fru-(2→6)-β-D-Fru-(2→1)-D-Tag and β-D-Fru-(2→1)-D-Tag. In vitro studies demonstrated the resistance of tagatose-based oligosaccharides to intestinal digestion and their prebiotic properties, providing insights into their structure-function relationship. β-D-Fru-(2→1)-D-Tag was the most resistant structure to small-intestinal digestion after three hours (99.8% remained unaltered). This disaccharide and the commercial FOS clustered in similar branches, indicating comparable modulatory properties on human fecal microbiota, and exerted a higher bifidogenic effect than unmodified tagatose. The bioconversion of selected rare sugars into β-fructosylated species with a higher degree of polymerization emerges as an efficient strategy to enhance the bioavailability of these carbohydrates and promote their interaction with the gut microbiota. These findings open up new opportunities for tailoring natural rare sugars, like D-tagatose and L-sorbose, to produce novel biosynthesized carbohydrates with functional and structural properties desirable for use as emerging prebiotics and low-calorie sweeteners.

Native intra-articular knee microbiome is a matter of facts: a systematic review of clinical evidence.

Growing interest surrounds the role of human gut microbiome in the development of degenerative pathologies such as osteoarthritis (OA), but microbes have recently been detected also in other sites previously considered to be sterile. Evidence emerged suggesting that even native and osteoarthritic knee joints may host several microbial species possibly involved in the osteoarthritic degeneration. This is the first systematic review critically collecting all the available evidence on the existence and composition of knee intra-articular microbiome. A systematic research on the PubMed, Cochrane and Google Scholar databases was performed. Human clinical studies investigating the presence of intra-articular microbiome in native osteoarthritic knee joints with next-generation sequencing techniques were collected. A total of eight studies were included reporting data on 255 knees. All the included studies reported evidence supporting the existence of an intra-articular microbiome in native knee joints, with detection rates varying from 5.8% to 100%. Bacteria from the Proteobacteria phylum were found to be among the most identified followed by the Actinobacteria, Firmicutes, Fusobacteria, and Bacteroideta phyla. Proteobacteria phylum were also found to be more common in osteoarthritic knees when compared to healthy joints. Furthermore, several pathways correlating those microbes to knee OA progression have been suggested and summarized in this review. Evidence collected in this systematic review suggests that the native knee joint, previously presumed to be a sterile environment, hosts a peculiar intra-articular microbiome with a unique composition. Furthermore, its alteration may have a link with the progression of knee osteoarthritis.

Characterising and preventing the gut microbiota's inactivation of trifluridine, a colorectal cancer drug

The gut microbiome can metabolise hundreds of drugs, potentially affecting their bioavailability and pharmacological effect. As most gut bacteria reside in the colon, drugs that reach the colon in significant proportions may be most impacted by microbiome metabolism. In this study the anti-colorectal cancer drug trifluridine was used as a model drug for characterising metabolism by the colonic microbiota, identifying correlations between bacterial species and individuals’ rates of microbiome drug inactivation, and developing strategies to prevent drug inactivation following targeted colonic delivery. High performance liquid chromatography and ultra-high performance liquid chromatography coupled with high resolution tandem mass spectrometry demonstrated trifluridine's variable and multi-route metabolism by the faecal microbiota sourced from six healthy humans. Here, four drug metabolites were linked to the microbiome for the first time. Metagenomic sequencing of the human microbiota samples revealed their composition, which facilitated prediction of individual donors’ microbial trifluridine inactivation. Notably, the abundance of Clostridium perfringens strongly correlated with the extent of trifluridine inactivation by microbiota samples after 2 hours (R2 = 0.8966). Finally, several strategies were trialled for the prevention of microbial trifluridine metabolism. It was shown that uridine, a safe and well-tolerated molecule, significantly reduced the microbiota's metabolism of trifluridine by acting as a competitive enzyme inhibitor. Further, uridine was found to provide prebiotic effects. The findings in this study greatly expand knowledge on trifluridine's interactions with the gut microbiome and provide valuable insights for investigating the microbiome metabolism of other drugs. The results demonstrate how protection strategies could enhance the colonic stability of microbiome-sensitive drugs.

A single amplified genome catalog reveals the dynamics of mobilome and resistome in the human microbiome

BackgroundThe increase in metagenome-assembled genomes (MAGs) has advanced our understanding of the functional characterization and taxonomic assignment within the human microbiome. However, MAGs, as population consensus genomes, often aggregate heterogeneity among species and strains, thereby obfuscating the precise relationships between microbial hosts and mobile genetic elements (MGEs). In contrast, single amplified genomes (SAGs) derived via single-cell genome sequencing can capture individual genomic content, including MGEs.ResultsWe introduce the first substantial SAG dataset (bbsag20) from the human oral and gut microbiome, comprising 17,202 SAGs above medium-quality without co-assembly. This collection unveils a diversity of bacterial lineages across 312 oral and 647 gut species, demonstrating different taxonomic compositions from MAGs. Moreover, the SAGs showed cellular-level evidence of the translocation of oral bacteria to the gut. We also identified broad-host-range MGEs harboring antibiotic resistance genes (ARGs), which were not detected in the MAGs.ConclusionsThe difference in taxonomic composition between SAGs and MAGs indicates that combining both methods would be effective in expanding the genome catalog. By connecting mobilomes and resistomes in individual samples, SAGs could meticulously chart a dynamic network of ARGs on MGEs, pinpointing potential ARG reservoirs and their spreading patterns in the microbial community.DX-3H-wDoVG35Spx9tFU_UVideo

Quercetin microgels alter gut metabolome and reverse oxidative damage invitro

Colonic delivery of quercetin using encapsulation techniques is an effective approach in maximizing quercetin efficacy against oxidative-stress related diseases such as inflammatory bowel disease. We hypothesized that colon-targeted delivery of quercetin with quercetin loaded alginate-chitosan microgels (ALQ) could alter colonic microbial metabolism regulating microbial metabolites production that may exert biological effects at the cellular level. To demonstrate this, ALQ were subjected to colonic fermentation using human fecal microbiota with empty microgels (AL) as control, and fermented fecal samples were collected at 0, 8, and 24 h. Short chain fatty acid analysis using gas chromatography showed that ALQ increased productions of acetic acid, while decreased isobutyric and isovaleric acid production. Semi-targeted metabolome scanning using Orbitrap mass spectrometer showed that the overall metabolome profile was remarkably different between AL and ALQ treatments at both 8 h and 24 h of fermentation. There were 9 metabolites at 8 h, and 54 metabolites at 24 h that were significantly regulated with more than 2-fold changes between AL and ALQ treatments. The metabolites included quercetin derived metabolites, amino acids and their derivatives, nucleotide derivatives, and organic acids. ALQ significantly modulated tyrosine metabolism, amino acids metabolic pathways, and the tricarboxylic acid cycle. These ALQ modulated metabolites in turn protected the Caco-2 cells from lipopolysaccharides induced injury, increased cellular antioxidant activities, and alleviated lipid oxidation induced by H2O2. Conclusively, ALQ could alter human fecal metabolome in vitro with significant shifts in key metabolites and exert antioxidant effects on cellular level, exhibiting potentials in colonic disease management.

Viroid-like colonists of human microbiomes.

Here, we describe "obelisks," a class of heritable RNA elements sharing several properties: (1) apparently circular RNA ∼1 kb genome assemblies, (2) predicted rod-like genome-wide secondary structures, and (3) open reading frames encoding a novel "Oblin" protein superfamily. A subset of obelisks includes a variant hammerhead self-cleaving ribozyme. Obelisks form their own phylogenetic group without detectable similarity to known biological agents. Surveying globally, we identified 29,959 distinct obelisks (clustered at 90% sequence identity) from diverse ecological niches. Obelisks are prevalent in human microbiomes, with detection in ∼7% (29/440) and ∼50% (17/32) of queried stool and oral metatranscriptomes, respectively. We establish Streptococcus sanguinis as a cellular host of a specific obelisk and find that this obelisk's maintenance is not essential for bacterial growth. Our observations identify obelisks as a class of diverse RNAs of yet-to-be-determined impact that have colonized and gone unnoticed in human and global microbiomes.

The human microbiome proofed by the Anthropocene: from correlation to causality and intervention

The deleterious effects of human activities on biodiversity in the vegetal and animal world, and on climate changes are now well-established facts. However, little is yet known on the impact of human activities on microbial diversity on the planet and more specifically on the human microbiota Large implementation of metagenomics allows exaustive microbial cataloguing with broad spatio-temporal resolution of human microbiota. A reduction in bacterial richness and diversity in the human microbiota, particularly in the intestinal tract, is now established and particularly obvious in the most industrialized regions of the planet. Massive, uncontrolled use of antibiotics, drastic changes in traditional food habits and some elements of the "global exposome" that remain to identify are usually considered as stressors accounting for this situation of "missing microbes". As a consequence, a dysbiotic situation develops, a "dysbiosis" being characterized by the erosion of the central core of shared bacterial species across individuals and the development of opportunistic "pathobionts" in response to a weaker barrier capacity of these impoverished microbiota. The current challenge is to establish a causality link between the extension of these dysbiotic situations and the steady emergence of epidemic, non-communicable diseases such as asthma, allergy, obesity, diabetes, autoimmune diseases and some cancers. Experimental animal models combined with controlled, prospective clinical interventions are in demand to consolidate causality links, with the understanding that in the deciphering of the mechanisms of alteration of the human-microbiome symbiosis resides a novel exciting chapter of medicine: "microbial medicine".

Comprehensive data optimization and risk prediction framework: machine learning methods for inflammatory bowel disease prediction based on the human gut microbiome data.

Over the past decade, the prevalence of inflammatory bowel disease (IBD) has significantly increased, making early detection crucial for improving patient survival rates. Medical research suggests that changes in the human gut microbiome are closely linked to IBD onset, playing a critical role in its prediction. However, the current gut microbiome data often exhibit missing values and high dimensionality, posing challenges to the accuracy of predictive algorithms. To address these issues, we proposed the comprehensive data optimization and risk prediction framework (CDORPF), an ensemble learning framework designed to predict IBD risk based on the human gut microbiome, aiding early diagnosis. The framework comprised two main components: data optimization and risk prediction. The data optimization module first employed triple optimization imputation (TOI) to impute missing data while preserving the biological characteristics of the microbiome. It then utilized importance-weighted variational autoencoder (IWVAE) to reduce redundant information from the high-dimensional microbiome data. This process resulted in a complete, low-dimensional representation of the data, laying the foundation for improved algorithm efficiency and accuracy. In the risk prediction module, the optimized data was classified using a random forest (RF) model, and hyperparameters were globally optimized using improved aquila optimizer (IAO), which incorporated multiple strategies. Experimental results on IBD-related gut microbiome datasets showed that the proposed framework achieved classification accuracy, recall, and F1 scores exceeding 0.9, outperforming comparison models and serving as a valuable tool for predicting IBD onset risk.

Rational treatment of acute rhinosinusitis in the context of increasing antibiotic resistance.

Acute rhinosinusitis is one of the most common diseases in the population, both in primary and specialist otolaryngological care. It is also responsible for a disturbingly high percentage of prescribed antibiotic therapy, regardless of the etiology of the disease. Despite the fact that acute viral and acute postviral rhinosinusitis dominate among the phenotypes of acute rhinosinusitis, and the development of acute bacterial rhinosinusitis occurs in only 0.5-2% of all cases in adults and 5-10% in children, antibiotics still remain an important element of treatment, despite alarming data on the growing antibiotic resistance and the adverse effect of antibiotics on the human microbiome, leading to dysbiosis. The discovery of antibiotics was one of the greatest achievements of modern medicine, but their inappropriate use leads to the gradual increase in the phenomenon of antibiotic resistance, considered one of the most serious public health problems, recognized by the WHO as one of the 10 greatest threats to human health in the 21<sup>st</sup> century. The unjustified use of antibiotics in outpatient care is the key to the growth of this problem, in parallel with the lack of patient compliance. The COVID pandemic has intensified this unfavourable trend. That is why the knowledge of antibiotic stewardship is so important. According to the guidelines, in the therapy of acute rhinosinusitis, symptomatic and anti-inflammatory treatment dominates, and antibiotic therapy has very strictly defined and limited indications. The latest guidelines also recommend herbal medicines, including BNO 1016, in the treatment of acute viral and postviral rhinosinusitis. Available studies indicate that it has a beneficial effect not only on shortening the duration of the disease and reducing symptoms, but also reduces the need for antibiotic treatment in acute rhinosinusitis. Complications of acute rhinosinusitis are relatively rare and are not related to taking antibiotics.

MVP: a modular viromics pipeline to identify, filter, cluster, annotate, and bin viruses from metagenomes.

While numerous computational frameworks and workflows are available for recovering prokaryote and eukaryote genomes from metagenome data, only a limited number of pipelines are designed specifically for viromics analysis. With many viromics tools developed in the last few years alone, it can be challenging for scientists with limited bioinformatics experience to easily recover, evaluate quality, annotate genes, dereplicate, assign taxonomy, and calculate relative abundance and coverage of viral genomes using state-of-the-art methods and standards. Here, we describe Modular Viromics Pipeline (MVP) v.1.0, a user-friendly pipeline written in Python and providing a simple framework to perform standard viromics analyses. MVP combines multiple tools to enable viral genome identification, characterization of genome quality, filtering, clustering, taxonomic and functional annotation, genome binning, and comprehensive summaries of results that can be used for downstream ecological analyses. Overall, MVP provides a standardized and reproducible pipeline for both extensive and robust characterization of viruses from large-scale sequencing data including metagenomes, metatranscriptomes, viromes, and isolate genomes. As a typical use case, we show how the entire MVP pipeline can be applied to a set of 20 metagenomes from wetland sediments using only 10 modules executed via command lines, leading to the identification of 11,656 viral contigs and 8,145 viral operational taxonomic units (vOTUs) displaying a clear beta-diversity pattern. Further, acting as a dynamic wrapper, MVP is designed to continuously incorporate updates and integrate new tools, ensuring its ongoing relevance in the rapidly evolving field of viromics. MVP is available at https://gitlab.com/ccoclet/mvp and as versioned packages in PyPi and Conda.IMPORTANCEThe significance of our work lies in the development of Modular Viromics Pipeline (MVP), an integrated and user-friendly pipeline tailored exclusively for viromics analyses. MVP stands out due to its modular design, which ensures easy installation, execution, and integration of new tools and databases. By combining state-of-the-art tools such as geNomad and CheckV, MVP provides high-quality viral genome recovery and taxonomy and host assignment, and functional annotation, addressing the limitations of existing pipelines. MVP's ability to handle diverse sample types, including environmental, human microbiome, and plant-associated samples, makes it a versatile tool for the broader microbiome research community. By standardizing the analysis process and providing easily interpretable results, MVP enables researchers to perform comprehensive studies of viral communities, significantly advancing our understanding of viral ecology and its impact on various ecosystems.

Understanding the role of the human gut microbiome in overweight and obesity.

The gut microbiome may be related to the prevalence of overweight and obesity, but high interindividual variability of the human microbiome complicates our understanding. Obesity often occurs concomitantly with micronutrient deficiencies that impair energy metabolism. Microbiota composition is affected by diet. Host-microbiota interactions are bidirectional. We propose three pathways whereby these interactions may modulate the gut microbiome and obesity: (1) ingested compounds or derivatives affecting small intestinal transit, endogenous secretions, digestion, absorption, microbiome balance, and gut barrier function directly affect host metabolism; (2) substrate availability affecting colonic microbial composition and contact with the gut barrier; and (3) microbial end products affecting host metabolism. The quantity/concentration, duration, and/or frequency (circadian rhythm) of changes in these pathways can alter the gut microbiome, disrupt the gut barrier, alter host immunity, and increase the risk of and progression to overweight and obesity. Host-specific characteristics (e.g., genetic variations) may further affect individual sensitivity and/or resilience to diet- and microbiome-associated perturbations in the colonic environment. In this narrative review, the effects of selected interventions, including fecal microbiota transplantation, dietary calorie restriction, dietary fibers and prebiotics, probiotics and synbiotics, vitamins, minerals, and fatty acids, on the gut microbiome, body weight, and/or adiposity are summarized to help identify mechanisms of action and research opportunities.

Gut microbiota plays pivotal roles in benign and malignant hematopoiesis.

Accumulated evidence emerges that dynamic changes in human gut microbiota and microbial metabolites can alter the ecological balance of symbiotic hosts. The gut microbiota plays a role in various diseases through different mechanisms. More and more attention has been paid to the effects that human microbiota extends beyond the gut. This review summarized the current understanding of the roles that gut microbiota plays in hematopoietic regulation and the occurrence and development of benign and malignant hematologic diseases. The progress of the application of microbiota in treatment was discussed in order to provide new insights into clinical diagnosis and treatment in the future.

Rodent models for oral microbiome research: considerations and challenges- a mini review.

Rodent models have been commonly employed in oral microbiota research to investigate the relationship between bacteria and oral disease. Nevertheless, to apply the knowledge acquired from studies conducted on rodents to a human context, it is crucial to consider the significant spatial and temporal parallels and differences between the oral microbiota of mice and humans. Initially, we outline the comparative physiology and microbiology of the oral cavity of rodents and humans. Additionally, we highlight the strong correlation between the oral microbiome of rodents and genetic makeup, which is influenced by factors including vendor, husbandry practices, and environmental conditions. All of these factors potentially impact the replicability of studies on rodent microbiota and the resulting conclusions. Next, we direct our attention toward the diversity in the microbiome within mice models of disease and highlight the diversity that may potentially affect the characteristics of diseases and, in turn, alter the ability to replicate research findings and apply them to real-world situations. Furthermore, we explore the practicality of oral microbial models for complex oral microbial diseases in future investigations by examining the concept of gnotobiotic and germ-free mouse models. Finally, we stress the importance of investigating suitable techniques for characterizing and managing genetically modified organisms. Future research should consider these aspects to improve oral microbiome research's translational potential.

Impact of microplastics pollution on ciprofloxacin bioaccumulation in the edible mussel (Perna viridis): implications for human gut health risks

Antibiotics and microplastics are prevalent pollutants in mariculture. Consuming contaminated bivalves can potentially endanger human health, but the impact of microplastics on antibiotics bioaccumulation in bivalves and the related health risks to consumer health risks is not fully understood. We obtained bivalves from a mariculture farm and set up exposure scenarios with ciprofloxacin (1μg/L) alone, microplastics (0.6mg/L) alone, or their combination on mussels for 2-weeks. We investigated ciprofloxacin accumulation and analyzed the effects of these pollutants on detoxification and intestinal microbiome changes. Furthermore, potential food safety hazards related to ingestion of antibiotic-tainted bivalves were also assessed. We found that the accumulation of the ciprofloxacin in bivalves was significantly aggravated by the presence of microplastics. There was a significant increase in the production of antioxidant substances in the host's haemolymph, and an enhanced synthesis of antioxidants by the predicted metabolic functions of the intestinal microbiome. Concomitantly, microplastics exacerbated intestinal dysfunction, with a reduction in beneficial Spirochaetes and an increase in pathogenic bacteria Treponema, which may lead to deterioration of detoxification in the host. Additionally, an assessment of human gut health risks was conducted on the residual ciprofloxacin in bivalves combined with human consumption habits. The estimated target hazard quotients and cancer risk were below safety thresholds, directly consuming contaminated bivalves poses little toxicity. However, with raw mussels consumption, the dietary exposure doses of ciprofloxacin to human gut microbiome exceeded minimal selective concentrations for resistance. This could promote the growth of potentially resistant bacteria, indicating a risk of antibiotic resistance.

Metatranscriptomics-guided discovery and characterization of a polyphenol-metabolizing gut microbial enzyme

Gut microbial catechol dehydroxylases are a largely uncharacterized family of metalloenzymes that potentially impact human health by metabolizing dietary polyphenols. Here, we use metatranscriptomics (MTX) to identify highly transcribed catechol-dehydroxylase-encoding genes in human gut microbiomes. We discover a prevalent, previously uncharacterized catechol dehydroxylase (Gp Hcdh) from Gordonibacter pamelaeae that dehydroxylates hydrocaffeic acid (HCA), an anti-inflammatory gut microbial metabolite derived from plant-based foods. Further analyses suggest that the activity of Gp Hcdh may reduce anti-inflammatory benefits of polyphenol-rich foods. Together, these results show the utility of combining MTX analysis and biochemical characterization for gut microbial enzyme discovery and reveal a potential link between host inflammation and a specific polyphenol-metabolizing gut microbial enzyme.

Metabolic adaptations of Escherichia coli to extended zinc exposure: insights into tricarboxylic acid cycle and trehalose synthesis

Balanced bacterial metabolism is essential for cell homeostasis and growth and can be impacted by various stress factors. In particular, bacteria exposed to metals, including the nanoparticle form, can significantly alter their metabolic processes. It is known that the extensive and intensive use of food and feed supplements, including zinc, in human and animal nutrition alters the intestinal microbiota and this may negatively impact the health of the host. This study examines the effects of zinc (zinc oxide and zinc oxide nanoparticles) on key metabolic pathways of Escherichia coli. Transcriptomic and proteomic analyses along with quantification of intermediates of tricarboxylic acid (TCA) were employed to monitor and study the bacterial responses. Multi-omics analysis revealed that extended zinc exposure induced mainly oxidative stress and elevated expression/production of enzymes of carbohydrate metabolism, especially enzymes for synthesis of trehalose. After the zinc withdrawal, E. coli metabolism returned to a baseline state. These findings shed light on the alteration of TCA and on importance of trehalose synthesis in metal-induced stress and its broader implications for bacterial metabolism and defense and consequently for the balance and health of the human and animal microbiome.