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Purpose: To describe the emerging evidence concerning etiologic factors and pathophysiologic mechanisms involved in peri-implant inflammatory diseases. Materials and Methods: An electronic search for articles published until November 2022 was conducted in MEDLINE by three independent reviewers to identify the manuscripts' reporting data on etiologic factors and pathophysiologic mechanisms associated with peri-implant diseases. Results: Current evidence suggests that peri-implant mucositis and peri-implantitis are inflammatory conditions linked to a microbial challenge. However, in recent years there has been increasing evidence indicating that certain peri-implant inflammatory conditions may not be primarily related to biofilm-mediated infectious processes but rather to other biologic mechanisms, such as a foreign body response. Conclusions: Current evidence in the dental and medical literature opens new avenues for a more complex interpretation of the etiopathogenetic factors involved in peri-implant diseases. A better understanding of various factors related to the host response, including dysbiosis mechanisms associated with changes in microbiota composition, is necessary for a more precise physiopathologic characterization of these diseases. [ABSTRACT FROM AUTHOR]

The D-enantiomers of L-amino acids are non-proteinogenic but widely present in foods. This is due to spontaneous racemization or processing, such as heating or alkali treatment, leading to substantial dietary exposure. Additional exposure to D-amino acids (D-AAs) comes from the human microbiota; D-AAs are present in bacterial surface proteoglycans, essential for bacterial competition and growth. Humans and other mammals have a complex set of genes for D-AA transport and degradation, and capacity to synthesize several D-AAs. Free D-AAs are present at low levels in human tissues and body fluids, yet they are apparently of considerable physiological and pathological importance. Amino acid transport regulates their presence and favors specific D-AAs, e.g. D-serine, D-aspartate, D-cysteine, and D-glutamate, over many others. Some of these D-AAs interact with the ubiquitous glutamate-gated Ca2+ channels, affecting signaling functions in most organs, especially the intestine, kidney, and brain. Consequently, the exposures, synthesis, local and systemic transport of D-AAs could be much more biologically important in humans than previously assumed, likely playing a role in gut-organ signaling and in many degenerative diseases. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • Obelisks are a phylogenetically distinct group of microbiome-associated, viroid-like RNAs • Found globally in diverse niches, obelisks also occur in human stool and oral microbiomes • The human oral bacterium Streptococcus sanguinis SK36 harbors a distinct "obelisk- S.s " • Under replete growth conditions, obelisk- S.s appears to be disposable for SK36 growth Obelisks are widespread RNA-based agents found in diverse environmental and human-associated microbiomes. These apparently unbranched and circular RNAs represent a previously uncharacterized class of genetic elements. [ABSTRACT FROM AUTHOR]

Berries represent an important source of bioactive compounds, among which, (poly)phenols are the main constituents. (Poly)phenols have been shown to have important biological activities and in particular, to take a relevant role in mediating the modulation of gut microbiota and human health. Gut microbiota constitute significant players in the metabolism of ingested (poly)phenols and consequently in their biological effects. However, the evidence regarding the mutual contribution between (poly)phenol intake and gut microbiota activity in humans is still unclear. The aim of the current systematic review was to collect and assess results from randomized clinical trials addressing the role of berries in the modulation of the gut microbiota composition and how this can contribute to the metabolism of berry (poly)phenols. When information was available, the interaction of berry-gut microbiota on human health was evaluated. A total of 16 trials were included and analyzed. Overall, berries and their (poly)phenols could represent a driver for the modulation of intestinal microbes. The gut microbiota catabolize (poly)phenols by producing bioactive metabolites which can positively affect both the composition of commensal microbiota and also the host health. [ABSTRACT FROM AUTHOR]

The human gut microbiota plays numerous roles in regulating host growth, the immune system, and metabolism. Age-related changes in the gut environment lead to chronic inflammation, metabolic dysfunction, and illness, which in turn affect aging and increase the risk of neurodegenerative disorders. Local immunity is also affected by changes in the gut environment. Polyamines are crucial for cell development, proliferation, and tissue regeneration. They regulate enzyme activity, bind to and stabilize DNA and RNA, have antioxidative properties, and are necessary for the control of translation. All living organisms contain the natural polyamine spermidine, which has anti-inflammatory and antioxidant properties. It can regulate protein expression, prolong life, and improve mitochondrial metabolic activity and respiration. Spermidine levels experience an age-related decrease, and the development of age-related diseases is correlated with decreased endogenous spermidine concentrations. As more than just a consequence, this review explores the connection between polyamine metabolism and aging and identifies advantageous bacteria for anti-aging and metabolites they produce. Further research is being conducted on probiotics and prebiotics that support the uptake and ingestion of spermidine from food extracts or stimulate the production of polyamines by gut microbiota. This provides a successful strategy to increase spermidine levels. [ABSTRACT FROM AUTHOR]

Contaminants, such as heavy metals (HMs), accumulate in the Arctic environment and the food web. The diet of the Indigenous Peoples of North Greenland includes locally sourced foods that are central to their nutritional, cultural, and societal health but these foods also contain high concentrations of heavy metals. While bacteria play an essential role in the metabolism of xenobiotics, there are limited studies on the impact of heavy metals on the human gut microbiome, and it is so far unknown if and how Arctic environmental contaminants impact the gut microbes of humans living in and off the Arctic environment. Using a multiomics approach including amplicon, metagenome, and metatranscriptome sequencing, we identified and assembled a near-complete (NC) genome of a mercury-resistant bacterial strain from the human gut microbiome, which expressed genes known to reduce mercury toxicity. At the overall ecological level studied through α- and β-diversity, there was no significant effect of heavy metals on the gut microbiota. Through the assembly of a high number of NC metagenome-assembled genomes (MAGs) of human gut microbes, we observed an almost complete overlap between heavy metal-resistant strains and antibiotic-resistant strains in which resistance genes were all located on the same genetic elements. [ABSTRACT FROM AUTHOR]

Bacteroides species are abundant, prevalent, and stable members of the human gut microbiota, making them a promising chassis for developing long-term interventions for chronic diseases. Engineering Bacteroides as in situ bio-factories, however, requires efficient protein secretion tools, which are currently lacking. Here, we systematically investigate methods to enable heterologous protein secretion in Bacteroides. We identify a collection of secretion carriers that can export functional proteins across multiple Bacteroides species at high titers. To understand the mechanistic drivers of Bacteroides secretion, we characterize signal peptide sequence features, post-secretion extracellular fate, and the size limit of protein cargo. To increase titers and enable flexible control of protein secretion, we develop a strong, self-contained, inducible expression circuit. Finally, we validate the functionality of our secretion carriers in vivo in a mouse model. This toolkit promises to enable expanded development of long-term living therapeutic interventions for chronic gastrointestinal disease. Bacteroides species are a promising chassis for developing living therapeutics, but this application is challenged by their poorly understood protein secretion abilities. Here, the authors report the discovery, characterization, and implementation of a molecular toolkit that enables efficient protein secretion in Bacteroides species. [ABSTRACT FROM AUTHOR]

Introduction: Reproductive endocrine disorders (RED), including polycystic ovary syndrome (PCOS), endometriosis (EMs), and female infertility (FI), significantly affect women's health globally, with varying prevalence across different regions. These conditions can be addressed through medication, surgical interventions, and lifestyle modifications. However, the limited understanding of RED's etiology and the substantial economic burden of its treatment highlight the importance of investigating its pathogenesis. Metabolites play a critical role in metabolic processes and are potentially linked to the development of RED. Despite existing studies suggesting correlations between metabolites and RED, conclusive evidence remains scarce, primarily due to the observational nature of these studies, which are prone to confounding factors. Methods: This study utilized Mendelian Randomization (MR) to explore the causal relationship between metabolites and RED, leveraging genetic variants associated with metabolite levels as instrumental variables to minimize confounding and reverse causality. Data were obtained from the Metabolomics GWAS Server and the IEU OpenGWAS project. Instrumental variables were selected based on their association with the human gut microbiota composition, and the GWAS summary statistics for metabolites, PCOS, EMs, and FI were analyzed. The MR-Egger regression and random-effects inverse-variance weighted (IVW) methods were employed to validate the causal relationship. Cochran's Q test was employed to evaluate heterogeneity, sensitivity analysis was performed using leave-one-out analysis, and for pleiotropy analysis, the intercept term of MR-Egger's method was investigated. Results: The MR analysis revealed significant associations between various metabolites and RED conditions. For instance, a positive association was found between 1-palmitoylglycerophosphocholine and PCOS, while a negative association was noted between phenylacetate and FI. The study identified several metabolites associated with an increased risk and others with protective effects against PCOS, EMs, and FI. These findings highlight the complex interplay between metabolites and RED, suggesting potential pathways through which these conditions could be influenced or treated. Conclusion: This MR study provides valuable insights into the causal relationship between metabolites and female reproductive endocrine disorders, suggesting that metabolic alterations play a significant role in the pathogenesis of PCOS, EMs, and FI, and offering a foundation for future research and therapeutic development. [ABSTRACT FROM AUTHOR]

Objective: Chronic migraine (CM) patients with medication overuse headache (MOH) were recently shown to be associated with leaky gut and inflammation. We aimed to investigate gut microbiota profiles of CM patients with MOH, and their correlations with inflammatory serum parameters, migraine food triggers, and comorbid anxiety and depression. Materials and methods: The study included women participants (32 CM patients with NSAID overuse headache, and 16 healthy non-headache sufferers). Migraine duration, monthly migraine headache days, presence of irritable bowel syndrome symptoms, and HADS-D and HADS-A scores were recorded. Serum samples were collected to measure circulating LPS, HMGB1, HIF-1α, and IL-6. The gut microbiota profiles of the patients were evaluated using fecal samples. Results: Serum LPS, HMGB1, HIF-1α, and IL-6 levels were significantly higher in the CM + MOH group compared to the healthy controls. HADS-A and HADS-D scores were considerably higher in the CM + MOH group compared to the healthy controls. In the microbiota analysis, alpha and beta diversities were similar between the two groups. The class Clostridia, the order Eubacteriales, and the genus Ruminococcus were less abundant in the CM + NSAID overuse headache group compared to the control group. At the genus level Desulfovibrio, Gemmiger, and Dialister and at the species level, Clostridium fessum, Blautia luti, Dorea longicatena, Eubacterium coprostanoligenes, and Gemmiger formicilis were more abundant in the CM + NSAID overuse headache group compared to the control group. Desulfovibrio, Gemmiger, Dialister, Ethanoligenens harbinense, Eubacterium coprostanoligenes, Dorea longicatena, and Thermoclostridium stercorarium showed positive correlations and Clostridia bacteria showed negative correlations with migraine food triggers. Positive correlations were found between LPS and Hapalosiphonaceae, HMGB1 and Melghirimyces, HIF1-α and Rouxeilla and Blautia luti, IL-6 and Melghirimyces and Ruminococcus. Conclusion: In CM patients with MOH, we have revealed the presence of dysbiosis towards an inflammatory state, and positive correlations were shown between altered gut microbiota and inflammatory serum parameters and migraine food triggers. [ABSTRACT FROM AUTHOR]

The human body is colonized by a diverse community of microorganisms that are crucial for human health, while microbiota homeostasis is modulated by both environmental and host-derived cues. Specific microbial species form surface-attached microcolonies surrounded by their self-generated extracellular polymeric substances called biofilms. These complex assemblies may protect commensal bacteria, serving as a barrier against pathogenic microorganisms as well as hostile conditions, thus creating structuralized microbial communities for complex microbial interactions. However, biofilms formed by pathogenic bacteria will lead to invasion and perturbance of microbiota homeostasis, potentially leading to dysbiosis and diseases. In this review, we provide an in-depth analysis of the multiple-species biofilms on microbiota homeostasis within the human body. We describe the nature of biofilms in various anatomical regions, emphasizing their protective role against pathogenic invasions and their potential roles in causing disease under certain conditions. We also explore the microbial interactions between biofilms and microbial communities, emphasizing the significant potential of biofilms to alter the structure and composition of microbial assemblages. Finally, we suggest the directions for future biofilm research to enhance our understanding of the pathogenesis of diseases related to microbial dysbiosis and human health. [ABSTRACT FROM AUTHOR]

The Tri-Service Microbiome Consortium (TSMC) was founded to enhance collaboration, coordination, and communication of microbiome research among DoD organizations and to facilitate resource, material and information sharing among consortium members, which includes collaborators in academia and industry. The 2023 annual symposium was a hybrid meeting held in Washington DC on 26–27 September 2023 concurrent with the virtual attendance, with oral and poster presentations and discussions centered on microbiome-related topics within five broad thematic areas: 1) Environmental Microbiome Characterization; 2) Microbiome Analysis; 3) Human Microbiome Characterization; 4) Microbiome Engineering; and 5) In Vitro and In Vivo Microbiome Models. Collectively, the symposium provided an update on the scope of current DoD and DoD-affiliated microbiome research efforts and fostered collaborative opportunities. This report summarizes the presentations and outcomes of the 7th annual TSMC symposium. [ABSTRACT FROM AUTHOR]

Introduction: Although the oral cavity and the gut are anatomically continuous regions of the gastrointestinal tract, research on the relationship between oral and gut microbiota remains sparse. Oral-gut bacterial translocation is mostly studied in pathological contexts, thus evidence of translocation in healthy conditions is still scarce. Studying the oral-gut microbiota relationship in humans in different life stages is necessary in order to understand how these microbial communities might relate throughout life. Methods: In this study, saliva and fecal samples were collected from healthy participants (39 children, 97 adults). Microbiota analysis was carried out by sequencing the V4 region of the 16S ribosomal RNA gene, followed by amplicon sequence variant (ASV) analysis. Results and discussion: Although the oral and gut microbiota are vastly different, a subset of 61 ASVs were present in both the oral cavity and gut of the same individual, and represented 1.6% of all ASVs detected. From these, 26 ASVs (classified into 18 genera: Actinomyces , Rothia , Bacteroides , Porphyromonas , Prevotella , Alistipes , Fusobacterium , Neisseria , Haemophilus , Akkermansia , Solobacterium , Granulicatella , Streptococcus , Gemella , Mogibacterium , Dialister , Veillonella , Christensenellaceae R-7 group) were present in both children and adults, suggesting the possibility of persistent colonization of both habitats by these microorganisms, initiating in childhood. Additionally, 62% of shared ASVs were more abundant in the oral cavity, indicating that oral-to-gut translocation may be the main route of translocation between environments, and highlighting that this phenomenon might be more common than previously thought in healthy individuals of all ages. [ABSTRACT FROM AUTHOR]

Background: Existing studies predominantly focused on the relationship between periodontitis and type 2 diabetes mellitus (T2DM), with limited data on the association between periodontitis and type 1 diabetes mellitus (T1DM). This study aimed to examine the impact of T1DM and periodontitis on the subgingival microbiome and levels of advanced glycation end-products (AGEs). Methods: Samples were collected from four groups: T1DM, periodontitis (P), T1DM with periodontitis (DP), and periodontally and systemically healthy controls (Control). Subgingival microbiome composition and AGE levels were assessed using 16S rRNA gene sequencing and enzyme-linked immunosorbent assay (ELISA), respectively. Correlations between clinical indexes, microbiome composition, and AGEs were analyzed using Spearman correlation coefficient. Results: Alpha and beta diversity analyses revealed significant differences in bacterial diversity between the DP group and other groups. Linear discriminant analysis effect size (LEfSe) analysis identified specific bacteria influencing each group: Acinetobacter, Leptotrichia, Raoultibacter, and Veillonella in the Control group; Tannerella, Porphyromonas, Filifactor, and Treponema in the P group; and Lactobacillales in T1DM individuals. Prevotella and Selenomonas were notably influential in the DP group. PICRUSt2 analysis showed pathways alterations were concentrated in cell motility, translation, cell growth and death and metabolism in the DP and P groups. Spearman correlation analysis indicated a positive correlation between AGEs and periodontitis or diabetes-related parameters and AGEs were positively correlated with Haemophilus and Arachnia. Conclusions: The findings suggested that the composition and function of the subgingival microbiome in the P group with or without T1DM were significantly different. Additionally, AGEs were involved in the development of periodontitis even in absence of hyperglycemia. [ABSTRACT FROM AUTHOR]

The work presented is a comprehensive review of the role of the human microbiota in the context of the COVID-19 pandemic. A diverse microbial community heavily colonizes the human body called the microbiota, with the gut microbiota being the most diverse. The composition of the microbiota varies in different parts of the body and changes with age, diet, and other environmental factors. Emerging evidence suggests that the gut microbiota plays a critical role in modulating the host immune response and may influence the severity of COVID-19. Patients with COVID-19 have significant alterations in their gut and respiratory microbiota, characterized by a depletion of beneficial commensal bacteria and an enrichment of opportunistic pathogens. These changes in microbiota composition are associated with elevated inflammatory markers, a dysregulated immune response, and more severe disease outcomes. In addition, changes in the gut microbiota can affect lung and brain function, influencing the severity of COVID-19 cases and neurological symptoms, as well as long-term neurological complications associated with the disease. Due to the importance of the microbiota in COVID-19, several therapeutic approaches targeting the microbiota have been proposed to improve outcomes in this disease, including fecal microbiota transplantation, probiotic and prebiotic supplementation, postbiotic or microbiota-derived metabolite supplementation, dietary interventions, and lifestyle strategies. Overall, the review highlights the critical role of the human microbiota in the pathogenesis and progression of COVID-19 and the potential of microbiota-targeted interventions to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Understanding the complex link between inflammation, gut health, and dietary amino acids is becoming increasingly important in the pathophysiology of inflammatory bowel disease (IBD). This study tested the hypothesis that a leucine-rich diet could attenuate inflammation and improve gut health in a mouse model of IBD. Specifically, we investigated the effects of a leucine-rich diet on dextran sulfate sodium (DSS)-induced colitis in germ-free (GF) SAMP1/YitFC (SAMP) mice colonized with human gut microbiota (hGF-SAMP). hGF-SAMP mice were fed one of four different diets: standard mouse diet (CHOW), American diet (AD), leucine-rich AD (AD + AA), or leucine-rich CHOW diet (CH + AA). Body weight, myeloperoxidase (MPO) activity, gut permeability, colonoscopy scores, and histological analysis were measured. Mice on a leucine-rich CHOW diet showed a decrease in fecal MPO prior to DSS treatment as compared to those on a regular diet (p > 0.05); however, after week five, prior to DSS, this effect had diminished. Following DSS treatment, there was no significant difference in gut permeability, fecal MPO activity, or body weight changes between the leucine-supplemented and control groups. These findings suggest that while a leucine-rich diet may transiently affect fecal MPO levels in hGF-SAMP mice, it does not confer protection against DSS-induced colitis symptoms or mitigate inflammation in the long term. [ABSTRACT FROM AUTHOR]

The salivary microbiota of Italian and sub-Saharan African individuals was investigated using Nanopore sequencing technology (ONT: Oxford Nanopore Technologies). We detected variations in community composition in relation to endogenous (ethnicity, sex, and diplotypic variants of the TRPV1 gene) and exogenous (sensitivity to capsaicin) factors. The results showed that Prevotella, Haemophilus, Neisseria, Streptococcus, Veillonella, and Rothia are the most abundant genera, in accordance with the literature. However, alpha diversity and frequency spectra differed significantly between DNA pools. The microbiota in African, male TRPV1 bb/ab diplotype and capsaicin low-sensitive DNA pools was more diverse than Italian, female TRPV1 aa diplotype and capsaicin high-sensitive DNA pools. Relative abundance differed at the phylum, genus, and species level. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of the study was to prospectively assess the microbiome and its influence on radiotherapy toxicity in patients with laryngeal cancer. Statistically significant risk factors for complications after radiotherapy were the percentage of Porphyromonas of at least 6.7%, the percentage of Fusobacterium of at least 2.6% and the percentage of Catonella of at least 2.6%. The importance of the microbiome in oncology has been confirmed in many studies. Effective radiotherapy treatment and the prevention of radiation-induced oral mucositis is a challenge in oncology. The microbiome may be an important part of personalized cancer treatment. The assessment of the microbiome of patients diagnosed with cancer may provide the opportunity to predict the response to treatment and its effectiveness. The influence of the microbiome may be important in predicting the risk group for radiotherapy treatment failure. The possibility of modifying the microbiome may become a goal to improve the prognosis of patients with laryngeal cancer. Fusobacterium, Porphyromonas and Catonella are important risk factors for radiation-induced oral mucositis in patients with laryngeal cancer. Introduction: Radiotherapy is an effective method of treating cancer and affects 50% of patients. Intensity-modulated radiotherapy (IMRT) is a modernized method of classical radiation used in the treatment of laryngeal cancer. Treatment with intent to preserve the larynx is not always safe or complication-free. The microbiome may significantly influence the effectiveness of oncological treatment, especially radiotherapy, and may also be modified by the toxic response to radiation. Objective: The aim of the study was to prospectively assess the microbiome and its influence on radiotherapy toxicity in patients with laryngeal cancer. Results: Statistically significant risk factors for complications after radiotherapy were the percentage of Porphyromonas of at least 6.7%, the percentage of Fusobacterium of at least 2.6% and the percentage of Catonella of at least 2.6%. Conclusions: The importance of the microbiome in oncology has been confirmed in many studies. Effective radiotherapy treatment and the prevention of radiation-induced oral mucositis is a challenge in oncology. The microbiome may be an important part of personalized cancer treatment. The assessment of the microbiome of patients diagnosed with cancer may provide the opportunity to predict the response to treatment and its effectiveness. The influence of the microbiome may be important in predicting the risk group for radiotherapy treatment failure. The possibility of modifying the microbiome may become a goal to improve the prognosis of patients with laryngeal cancer. Fusobacterium, Porphyromonas and Catonella are important risk factors for radiation-induced oral mucositis in patients with laryngeal cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is the most common cancer type and the leading cause of mortality for women worldwide. The microbiome influences various cancer therapies, including radiotherapy. Thus, radiotherapy-derived metabolites and microbiome composition may affect cancer progression and treatment response, and vice versa. This review explores this bidirectional relationship as well as providing current evidence and future perspectives in this field. The gut microbiome has emerged as a crucial player in modulating cancer therapies, including radiotherapy. In the case of breast cancer, the interplay between the microbiome and radiotherapy-derived metabolites may enhance therapeutic outcomes and minimize adverse effects. In this review, we explore the bidirectional relationship between the gut microbiome and breast cancer. We explain how gut microbiome composition influences cancer progression and treatment response, and how breast cancer and its treatments influence microbiome composition. A dual role for radiotherapy-derived metabolites is explored in this article, highlighting both their therapeutic benefits and potential hazards. By integrating genomics, metabolomics, and bioinformatics tools, we present a comprehensive overview of these interactions. The study provides real-world insight through case studies and clinical trials, while therapeutic innovations such as probiotics, and dietary interventions are examined for their potential to modulate the microbiome and enhance treatment effectiveness. Moreover, ethical considerations and patient perspectives are discussed, ensuring a comprehensive understanding of the subject. Towards revolutionizing treatment strategies and improving patient outcomes, the review concludes with future research directions. It also envisions integrating microbiome and metabolite research into personalized breast cancer therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the fecal and tumor microbiome as potential biomarkers of tumor response to neoadjuvant immunotherapy in combination with chemoradiation. We performed 16S rRNA amplicon sequencing on fecal and tumor samples, as well as fecal metabolomics, on biosamples collected from patients with resectable esophageal or gastroesophageal junction carcinoma before and during treatment. The fecal microbiome of patients whose tumors achieved a pathologic complete response revealed enrichment in sphingolipid and primary bile acids, with corresponding elevated abundance of several bacterial species: Roseburis inulinivorans, Ruminococcus callidus, and Fusicantenibacter saccharivorans. While these results provide initial insight, further study is necessary to validate these data and determine how microbes alter the immune response with neoadjuvant immunotherapy. Background: Preclinical and clinical data indicate that chemoradiotherapy (CRT) in combination with checkpoint inhibitors may prime an anti-tumor immunological response in esophageal cancer. However, responses to neoadjuvant therapy can vary widely and the key biomarkers to determine response remain poorly understood. The fecal microbiome is a novel and potentially modifiable biomarker of immunotherapy response, and both fecal and tumor microbes have been found to associate with outcomes in esophageal cancer. Methods: Fecal and tumor samples were collected from patients with stage II–III resectable esophageal or gastroesophageal junction carcinoma treated with neoadjuvant immune checkpoint inhibitors (ICIs) plus CRT prior to surgical resection. Microbiome profiles were analyzed by 16S rRNA amplicon sequencing and taxonomic data were integrated with fecal metabolite analysis to assess microbial function. Results: The fecal microbiome of patients with pathological complete response (PCR) grouped in distinct clusters compared to patients with residual viable tumor (RVT) by Bray–Curtis diversity metric. Integrated taxonomic and metabolomic analysis of fecal samples identified a sphingolipid and primary bile acid as enriched in the PCR, the levels of which correlated with several bacterial species: Roseburis inulinivorans, Ruminococcus callidus, and Fusicantenibacter saccharivorans. Analysis of the tumor microbiome profiles identified several bacterial genera previously associated with esophageal tumors, including Streptococcus and Veillonella. Conclusions: These results further characterize the fecal and tumor microbiome of patients with operable esophageal cancer and identify specific microbes and metabolites that may help elucidate how microbes contribute to tumor response with neoadjuvant CRT combined with ICI. [ABSTRACT FROM AUTHOR]

In numerous countries, the utilization of plants for both nutritional and therapeutic purposes is a common practice. However, the inadvertent use of these plants can pose risks due to their active molecules or microbiota. The traditional use of Herniaria glabra L. (H. glabra) plant in treating various diseases is well-known; however, its application in yogurt production raises concerns. In this study, Bacillus pumilus isolated from H. glabra was identified through 16s rRNA sequencing and MALDI-TOF MS (Matriks Assisted Lazer Desorption Ionization Time of Flight Massspectrometry). The bacterium's resistance under simulated gastrointestinal tract (GIT) conditions was assessed, followed by investigations into its aggregation ability, antibiotic resistance, hemolytic activity, and antagonistic potential through in vitro tests. The study revealed that B. pumilus exhibited 100% resistance to GIT conditions. Notably, the bacterium demonstrated strong autoaggregation (34.48%) and coaggregation abilities (49.82% for Escherichia coli, 49.13% for Listeria monocytogenes), signifying a potent aggregative potential. Sensitivity to most tested antibiotics was observed, while no antagonistic activity against tested bacteria was evident. Furthermore, the bacterium exhibited β-hemolytic activity, indicative of potential virulence. The findings suggest that this resistant yet virulent bacterium, with its hemolytic activity, could disrupt the GIT balance, posing serious health risks. The study underscores the need for caution and awareness regarding the potential dangers posed by bacteria in plant microbiota in herbal therapies. [ABSTRACT FROM AUTHOR]

Host‐associated microbiomes are thought to play a key role in host physiology and fitness, but this conclusion mainly derives from systems biased towards animal models and humans.While many studies on non‐model and wild animals have characterised the taxonomic diversity of their microbiomes, few have investigated the functional potential of these microbial communities.Functional 'omics' approaches, such as metagenomics, metatranscriptomics and metabolomics, represent promising techniques to probe the significance of host‐associated microbiomes in the wild.In this review, we propose to (1) briefly define the main available functional omics tools along with their strengths and limitations, (2) summarise the key advances enabled by omics tools to understand microbiome function in human and animal models, (3) showcase examples of how these methods have already brought invaluable insights into wild host microbiomes and (4) provide guidelines on how to implement these tools to address outstanding questions in the field of wild animal microbiomes.To conclude, we suggest that, building on knowledge derived from cheaper, more traditional approaches (e.g. 16S metabarcoding and qPCR), functional omics tools represent a promising approach to test hypotheses regarding the ecological and evolutionary significance of the resident microbiota in wild animals. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Background: Cervical ripening is a multifactorial outcome, and the association between cervical ripening and vaginal microbiota remains unexplored in term primiparous women. A new sequencing technology, microbiome 2bRAD sequencing (2bRAD-M) that provides a higher level of species discrimination compared to amplicon sequencing. We applied 2bRAD-M to analyze the vaginal microbiota in a population with variations in cervical ripeness and to explore potential microbiota factors influencing cervical ripening. Methods: A total of 30 full-term primigravid women participated in this study, with 15 belonging to the low scoring group of cervical ripeness and 15 to the high scoring group. Clinical information was collected from the participants, and the vaginal microbiota and community structure of both groups were analyzed using 2bRAD-M sequencing. Microbiota diversity and differential analyses were conducted to explore potential factors influencing cervical ripening. Results: A total of 605 species were detected. There was no difference in vaginal microbiota diversity between the two groups, and the vaginal microbial composition was structurally similar. In the two groups, Lactobacillus crispatus and Lactobacillus iners were identified as the two pivotal species through random forest analysis. Concurrent, extensive and close connections between species within the two groups were observed in the correlation analysis, influencing the aforementioned two species. Pairwise comparisons showed that Sphingomonas (P = 0.0017) and three others were abundant in high scoring group, while Alloprevotella (P = 0.0014), Tannerella (P = 0.0033), Bacteroides (P = 0.0132), Malassezia (P = 0.0296), Catonella (P = 0.0353) and Pseudomonas (P = 0.0353) and so on showed higher abundance in low scoring group. Linear discriminant analysis effect size identified 29 discriminative feature taxa. Conclusion: For the first time, vaginal microbiota was sequenced using 2bRAD-M. With a relatively simple structure, a more stable vaginal microbiota is associated with higher cervical ripeness, and certain microorganisms, such as Sphingomonas, may play a beneficial role in cervical ripening. [ABSTRACT FROM AUTHOR]

There is a growing focus on understanding the role of the male microbiome in fertility issues. Although research on the bacterial communities within the male reproductive system is in its initial phases, recent discoveries highlight notable variations in the microbiome's composition and abundance across distinct anatomical regions like the skin, foreskin, urethra, and coronary sulcus. To assess the relationship between male genitourinary microbiome and reproduction, we queried various databases, including MEDLINE (available via PubMed), SCOPUS, and Web of Science to obtain evidence-based data. The literature search was conducted using the following terms "gut/intestines microbiome," "genitourinary system microbiome," "microbiome and female/male infertility," "external genital tract microbiome," "internal genital tract microbiome," and "semen microbiome." Fifty-one relevant papers were analyzed, and eleven were strictly semen quality or male fertility related. The male microbiome, especially in the accessory glands like the prostate, seminal vesicles, and bulbourethral glands, has garnered significant interest because of its potential link to male fertility and reproduction. Studies have also found differences in bacterial diversity present in the testicular tissue of normozoospermic men compared to azoospermic suggesting a possible role of bacterial dysbiosis and reproduction. Correlation between the bacterial taxa in the genital microbiota of sexual partners has also been found, and sexual activity can influence the composition of the urogenital microbiota. Exploring the microbial world within the male reproductive system and its influence on fertility opens doors to developing ways to prevent, diagnose, and treat infertility. The present work emphasizes the importance of using consistent methods, conducting long-term studies, and deepening our understanding of how the reproductive tract microbiome works. This helps make research comparable, pinpoint potential interventions, and smoothly apply microbiome insights to real-world clinical practices. [ABSTRACT FROM AUTHOR]

[Display omitted] • Natural material manufactured using soil and plant has the potential to mimic exposure to diverse environmental microbiota. • The natural material retains a high diversity of microbiota found in the natural environment. • Sterilized natural material is safe for use in immune-mediated disease-prone mice. It has been suggested that reduced contact with microbiota from the natural environment contributes to the rising incidence of immune-mediated inflammatory disorders (IMIDs) in western, highly urbanized societies. In line with this, we have previously shown that exposure to environmental microbiota in the form of a blend comprising of soil and plant-based material (biodiversity blend; BDB) enhances the diversity of human commensal microbiota and promotes immunoregulation that may be associated with a reduced risk for IMIDs. To provide a framework for future preclinical studies and clinical trials, this study describes how the preparation of BDB was standardized, its microbial content analysed and safety assessments performed. Multiple batches of BDB were manufactured and microbial composition analysed using 16S rRNA gene sequencing. We observed a consistently high alpha diversity and relative abundance of bacteria normally found in soil and vegetation. We also found that inactivation of BDB by autoclaving effectively inactivates human and murine bacteria, viruses and parasites. Finally, we demonstrate that experimental mice prone to develop IMIDs (non-obese diabetic, NOD, mouse model) can be exposed to BDB without causing adverse effects on animal health and welfare. Our study provides insights into a potentially safe, sustainable, and cost-effective approach for simulating exposure to natural microbiota, which could have substantial impacts on health and socio-economic factors. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a genetically predisposed allergic inflammatory dermatosis with chronic, pruritic, and recurrent features. Patients with AD have dry and itchy skin, often accompanied by chronic eczematous lesions, allergic rhinitis, or asthma, which has a considerable impact on their daily lives. With advances in genome sequencing technology, it has been demonstrated that microorganisms are involved in this disease, and the microorganisms associated with AD are attracting considerable research attention. An increasing number of studies conducted in recent years have demonstrated that an imbalanced microbiome in AD patients has substantial impact on disease prognosis, and the causes are closely tied to various immune mechanisms. However, the involvement of microorganisms in the pathogenesis of AD remains poorly understood. In this paper, we review the advances in research on the immunological mechanisms of the skin microbiome, intestinal microbiome, and lung microbiome that are related to AD prognosis and immunotherapy protocols. It is hoped that this approach will lay the foundation for exploring the pathogenesis of and emerging treatments for AD. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether oral microbiome diversity is associated with all‐cause mortality in the general US population and in individuals with chronic diseases. Materials and Methods: We included 8224 individuals with oral microbiome diversity data from the National Health and Nutrition Examination Survey (2009–2012), representing 164,000,205 US adults, using a survey‐weighted analysis method. Cox regression analyses were performed to identify the association between oral microbiome diversity and all‐cause mortality. Results: During a survey‐weighted mean follow‐up period of 8.86 years, 429 all‐cause deaths (survey‐weighted number: 7,124,920) occurred in 8224 participants. Cox regression analysis revealed that higher oral microbiome diversity was significantly associated with a lower all‐cause mortality risk. Significant differences in all‐cause mortality risk were observed among the different clusters based on oral microbiome β‐diversity (log‐rank p < 0.001). Subgroup analyses revealed that the oral microbiome diversity was independently associated with all‐cause mortality in individuals with diabetes mellitus and hypertension. A multivariate logistic regression model showed that current smoking and antibiotic use were significantly associated with lower oral microbiome α diversity. Conclusions: Higher oral microbiome diversity was significantly associated with a lower all‐cause mortality risk in the general US population and in individuals with diabetes mellitus and hypertension. [ABSTRACT FROM AUTHOR]

Aim: To examine the independent and joint associations of oral microbiome diversity and diet quality with risks of all‐cause and cause‐specific mortality. Materials and Methods: We included 7,055 eligible adults from the U.S. National Health and Nutrition Examination Survey (NHANES). Oral microbiome diversity was measured with α‐diversity, including the Simpson Index, observed amplicon sequence variants (ASVs), Faith's phylogenetic diversity, and Shannon–Weiner index. Dietary quality was assessed using the Healthy Eating Index‐2015 (HEI‐2015). Cox proportional hazard models were used to assess the corresponding associations. Results: During a mean follow‐up of 9.0 years, we documented 382 all‐cause deaths. We observed independent associations of oral microbiome diversity indices and dietary quality with all‐cause mortality (hazard ratio [HR] = 0.63; 95% confidence interval [CI]: 0.49–0.82 for observed ASVs; HR = 0.68, 95% CI: 0.52–0.89 for HEI‐2015). Jointly, participants with the highest tertiles of both oral microbiome diversity (in Simpson index) and HEI‐2015 had the lowest hazard of mortality (HR = 0.37, 95% CI: 0.23–0.60). In addition, higher oral microbiome diversity was associated with lower risks of deaths from cardiometabolic disease and cancer. Conclusions: Higher oral microbiome α‐diversity and diet quality were independently associated with lower risk of mortality. [ABSTRACT FROM AUTHOR]

Aim: To describe the microbiological composition of subgingival dental plaque and molecular profile of gingival crevicular fluid (GCF) of periodontal furcation‐involved defects. Materials and Methods: Fifty‐seven participants with periodontitis contributed with a degree II–III furcation involvement (FI), a non‐furcation (NF) periodontal defect and a periodontally healthy site (HS). Subgingival plaque was analysed by sequencing the V3–V4 region of the 16S rRNA gene, and a multiplex bead immunoassay was carried out to estimate the GCF levels of 18 GCF biomarkers. Aiming to explore inherent patterns and the intrinsic structure of data, an AI‐clustering method was also applied. Results: In total, 171 subgingival plaque and 84 GCF samples were analysed. Four microbiome clusters were identified and associated with FI, NF and HS. A reduced aerobic microbiota (p =.01) was detected in FI compared with NF; IL‐6, MMP‐3, MMP‐8, BMP‐2, SOST, EGF and TIMP‐1 levels were increased in the GCF of FI compared with NF. Conclusions: This is the first study to profile periodontal furcation defects from a microbiological and inflammatory standpoint using conventional and AI‐based analyses. A reduced aerobic microbial biofilm and an increase of several inflammatory, connective tissue degradation and repair markers were detected compared with other periodontal defects. [ABSTRACT FROM AUTHOR]

Aims: The review aimed to summarise and discuss findings focused on therapeutic probiotic and prebiotic interventions in eating disorders (ED). Methods: Using PubMed/MEDLINE, Cochrane Library, and Web of Science all published studies were retrieved until February 2023, following PRISMA guidelines. From the 111 initial studies, 5 met the inclusion criteria for this review. Results: All studies included in this narrative review were focused on anorexia nervosa (AN). Three longitudinal, randomised, controlled trials aimed to evaluate interventions with probiotics (Lactobacillus reuteri, yoghurt with Lactobacillus, and Streptococcus) in children and adolescents. These studies primarily emphasised medical outcomes and anthropometric measures following the administration of probiotics. However, the findings yielded mixed results in terms of short‐term weight gain or alterations in specific immunological parameters. With a lower level of evidence, supplementation with synbiotics (probiotic + prebiotic) has been associated with improvements in microbiota diversity and attenuation of inflammatory responses. Conclusions: Research on probiotics and prebiotics in ED is limited, primarily focussing on anorexia nervosa (AN). Their use in AN regarding medical and anthropometric outcomes needs further confirmation and future research should be warranted to assess their impact on psychological and ED symptomatology, where there is a notable gap in the existing literature. Highlights: Research based on probiotic and prebiotic therapeutic interventions in eating disorders (ED) is still scarce.Available evidence comes particularly from randomised controlled trials in anorexia nervosa (AN), evaluating the effects of probiotics on medical outcomes and anthropometric measures.Future studies should explore the impact of probiotic and prebiotic interventions specifically on eating psychopathology in AN and other ED. [ABSTRACT FROM AUTHOR]

Reuterin, a mixture of different forms of 3-hydroxypropanal (3-HPA), including HPA hydrate and HPA dimer, is an antimicrobial compound converted from glycerol by Lactobacillus reuteri and other strains. Although its antimicrobial function may be related to its interaction with thiol groups, its temperature stability and effect on the gut environment remain unclear. The present study evaluated the antimicrobial effects and activity of reuterin against Escherichia coli and Salmonella typhimurium. Utilization of a reliable in vitro gut microbiome fermentation system revealed that reuterin has a modulatory effect on the gut microbial community. Reuterin treatment completely inhibited H2 and NH3 production in the gut and significantly enhanced the synthesis of branched short-chain fatty acids. 16s rRNA sequencing indicated that reuterin promoted the growth of Proteobacteria and Bacteroidetes in the in vitro system and significantly modulated gut microbiota composition. [ABSTRACT FROM AUTHOR]

Infections with the human papillomavirus (HPV) are one of the most common sexually transmitted diseases and are the main cause of precancerous changes and cervical cancer development. However, mere infection does not guarantee the development of disease or carcinogenesis. For this to occur, high-risk types of HPV must integrate into the host cell genome, transitioning into a persistent form of infection. Following the discovery of risk factors for HPV infection and factors predisposing infection to a persistent form, the number of studies investigating the correlation between vaginal dysbiosis and infection has significantly increased. Numerous studies document a significant association between the state of vaginal bacterial flora and HPV infection, leading to the development of plentiful studies on infection pathogenesis, risk factors, prevention, and treatment methods using bacteria. In this paper, based on recently published studies and current state of science knowledge, we will outline the topic of vaginal microbiome, emphasize the importance of bacteria inhabiting the vagina for human health, and identify the problem of changes in vaginal microflora. We would like to contribute to the dissemination of knowledge about the vaginal microbiome and general knowledge about taking care of its health. We will also summarize available treatment methods based on bacterial environment and discuss those methods for which research is currently underway or should be initiated. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Accurate taxonomic profiling of the human microbiome composition is crucial for linking microbial species to health outcomes. Therefore, we created the Clinical Microbiomics Human Microbiome Profiler (CHAMP), a comprehensive tool designed for the profiling of prokaryotes, eukaryotes, and viruses across all body sites. Methods: CHAMP uses a reference database derived from 30,382 human microbiome samples, covering 6,567 prokaryotic and 244 eukaryotic species, as well as 64,003 viruses. We benchmarked CHAMP against established profiling tools (MetaPhlAn 4, Bracken 2, mOTUs 3, and Phanta) using a diverse set of in silico metagenomes and DNA mock communities. Results: CHAMP demonstrated unparalleled species recall, F1 score, and significantly reduced false positives compared to all other tools benchmarked. The false positive relative abundance (FPRA) for CHAMP was, on average, 50-fold lower than the second-best performing profiler. CHAMP also proved to be more robust than other tools at low sequencing depths, highlighting its application for low biomass samples. Discussion: Taken together, this establishes CHAMP as a best-in-class human microbiome profiler of prokaryotes, eukaryotes, and viruses in diverse and complex communities across low and high biomass samples. [ABSTRACT FROM AUTHOR]

Background: Over the years, numerous studies have explored the relationship between gut microbiota and lower extremity deep vein thrombosis (LEDVT) and pulmonary embolism (PE). The present study utilized Mendelian randomization (MR) to assess the causal link between gut microbiota and LEDVT combined with PE. Methods: Human gut microbiota genome-wide association study (GWAS) summary data from the MiBioGen consortium (n  =  18,340) were utilized. Summary-level data on LEDVT (2,116 cases and 359,078 controls) and LEDVT combined with PE (4,319 cases and 356,875 controls) were obtained from the IEU Open GWAS project. MR analysis was conducted using the inverse variance weighted (IVW) method as the primary analysis. Additionally, MR-Egger, weighted median, weighted mode, and simple mode were employed as supplementary methods. Sensitivity analyses, including tests for heterogeneity and horizontal pleiotropy, were performed. Lastly, reverse MR analysis was performed. Results: The IVW analyses revealed seven causal relationships between genetic liability in the gut microbiota and LEDVT and five causal relationships between genetic liability in the gut microbiota and LEDVT combined with PE. The intersection of these outcomes identified that the genus Butyricicoccus reduced the risk of both LEDVT and LEDVT combined with PE, while the genus Clostridium innocuum increased the risk for both conditions. Conclusion: This study demonstrates that the gut microbiota is causally associated with LEDVT and LEDVT combined with PE. Our findings provide valuable insights into the underlying mechanisms and suggest potential avenues for further clinical investigations of these conditions. [ABSTRACT FROM AUTHOR]

Background: Recent findings highlight the significant impact of intestinal fungi on the complex makeup of the gut microbiota and human health, challenging past oversights. However, a lack of thorough systematic and quantitative analyses remains. This study aims to address this gap by thoroughly examining the current research on gut fungi. Through analyzing developments and unique features in this area, our goal is to foster a deeper understanding and identify future research pathways. Methods: We performed an extensive bibliometric analysis on documents from 2000 to 2023, sourced from the Web of Science Core Collection (WoSCC). Utilizing advanced visualization tools such as VOSviewer, CiteSpace, and Bibliometrix R, we meticulously examined and illustrated the data in scientific landscapes and networks. Results: A total of 1434 papers were analyzed, revealing a substantial increase in publication volume over the past two decades, particularly in 2020. Contributions came from 67 countries, 2178 institutions, and 8,479 authors. China led in publication output with 468 articles, followed by the University of California with 84 articles, and ZHANG F as the most prolific author with 17 articles. Emerging research areas such as “Fungal-Bacteria Interactions,” “Gut Fungus and Gut-Brain Axis,” and “Gut Fungus and Immunity” are expected to attract growing interest in the future. Conclusion: This extensive bibliometric analysis offers a current overview of scholarly efforts concerning intestinal fungi, highlighting the predominant landscape in this field. These insights can assist scholars in identifying appropriate publication avenues, forming collaborative relationships, and enhancing understanding of key themes and emerging areas, thereby stimulating future research endeavors. [ABSTRACT FROM AUTHOR]

The interplay between human microbiota and various physiological systems has garnered significant attention in recent years. The gut microbiota plays a critical role in maintaining physiological homeostasis and influences various aspects of human health, particularly via the gut brain axis. Since 2017, the challenging concept of the gut-retina axis has emerged thanks to a network analysis emphasizing the potential role of the gut microbiota disruption in the development of the age-related macular degeneration and further retinal damages. Many other ocular disorders have been linked to the dysbiosis of the gut microbiota, including uveitis and glaucoma. It has been shown that age related macular degeneration can be prevented or reversed using a diet that induces changes in the gut microbiota. The potential link between the gut microbiota as well as others types of microbiota such as the ocular surface microbiota and the development/progression of age related as well as inherited retinal degenerations and other degenerative eye diseases, has recently been broadened. Therefore, the pathogenesis of several eye diseases has recently been associated with a larger perception called the gut eye axis. This minireview examines the potential mechanisms underlying the gut eye axis and suggests implications for the management of eye diseases. By understanding the modulation of the gut microbiota and its impact on eye disease, this minireview provides insight into potential therapeutic interventions and avenues for future research. [ABSTRACT FROM AUTHOR]

Background: The prevalence of age-related disorders, particularly in neurological and cardiovascular systems, is an increasing global health concern. Mesenchymal stem cell (MSC) therapy, particularly using human umbilical cord-derived MSCs (HUCMSCs), has shown promise in mitigating these disorders. This study investigates the effects of HUCMSCs on aging-related conditions in a senescence-accelerated mouse model (SAMP8), with a focus on DNA damage, gut microbiota alterations, and metabolic changes. Methods: SAMP8 mice were treated with clinical-grade HUCMSCs via intraperitoneal injections. Behavioral and physical assessments were conducted to evaluate cognitive and motor functions. The Single-Strand Break Mapping at Nucleotide Genome Level (SSiNGLe) method was employed to assess DNA single-strand breaks (SSBs) across the genome, with particular attention to exonic regions and transcription start sites. Gut microbiota composition was analyzed using 16S rRNA sequencing, and carboxyl metabolomic profiling was performed to identify changes in circulating metabolites. Results: HUCMSC treatment significantly improved motor coordination and reduced anxiety in SAMP8 mice. SSiNGLe analysis revealed a notable reduction in DNA SSBs in MSC-treated mice, especially in critical genomic regions, suggesting that HUCMSCs may mitigate age-related DNA damage. The functional annotation of the DNA breaktome indicated a potential link between reduced DNA damage and altered metabolic pathways. Additionally, beneficial alterations in gut microbiota were observed, including an increase in short-chain fatty acid (SCFA)-producing bacteria, which correlated with improved metabolic profiles. Conclusion: The administration of HUCMSCs in SAMP8 mice not only reduces DNA damage but also induces favorable changes in gut microbiota and metabolism. The observed alterations in DNA break patterns, along with specific changes in microbiota and metabolic profiles, suggest that these could serve as potential biomarkers for evaluating the efficacy of HUCMSCs in treating age-related disorders. This highlights a promising avenue for the development of new therapeutic strategies that leverage these biomarkers, to enhance the effectiveness of HUCMSC-based treatments for aging-associated diseases. [ABSTRACT FROM AUTHOR]

Background: Information on the comparison of blood microbiota between human immunodeficiency virus (HIV)-infected and HIV-uninfected patients with suspected sepsis by metagenomic next-generation sequencing (mNGS) is limited. Methods: Retrospectively analysis was conducted in HIV-infected and HIV-uninfected patients with suspected sepsis at Changsha First Hospital (China) from March 2019 to August 2022. Patients who underwent blood mNGS testing were enrolled. The blood microbiota detected by mNGS were analyzed. Results: A total of 233 patients with suspected sepsis who performed blood mNGS were recruited in this study, including 79 HIV-infected and 154 HIV-uninfected patients. Compared with HIV-uninfected patients, the proportions of mycobacterium (p = 0.001), fungus (p < 0.001) and viruses (p < 0.001) were significantly higher, while the proportion of bacteria (p = 0.001) was significantly lower in HIV-infected patients. The higher positive rates of non-tuberculous mycobacteriosis (NTM, p = 0.022), Pneumocystis jirovecii (P. jirovecii) (p = 0.014), Talaromyces marneffei (T. marneffei) (p < 0.001) and cytomegalovirus (CMV) (p < 0.001) were observed in HIV-infected patients, compared with HIV-uninfected patients. In addition, compared with HIV-uninfected patients, the constituent ratio of T. marneffei (p < 0.001) in the fungus spectrum were significantly higher, while the constituent ratios of Candida (p < 0.001) and Aspergillus (p = 0.001) were significantly lower in HIV-infected patients. Conclusions: Significant differences in the blood microbiota profiles exist between HIV-infected and HIV-uninfected patients with suspected sepsis. [ABSTRACT FROM AUTHOR]

DNA transfer is ubiquitous in the human gut microbiota, especially among species of the order Bacteroidales. In silico analyses have revealed hundreds of mobile genetic elements shared between these species, yet little is known about the phenotypes they encode, their effects on fitness, or pleiotropic consequences for the recipient's genome. In this work, we show that acquisition of a ubiquitous integrative conjugative element (ICE) encoding a type VI secretion system (T6SS) shuts down the native T6SS of Bacteroides fragilis. Despite inactivating this T6SS, ICE acquisition increases the fitness of the B. fragilis transconjugant over its progenitor by arming it with the new T6SS. DNA transfer causes the strain to change allegiances so that it no longer targets ecosystem members with the same element yet is armed for communal defense. [ABSTRACT FROM AUTHOR]

Background: The awareness of the association between the gut microbiota and human intelligence levels is increasing, but the findings are inconsistent. Furthermore, few research have explored the potential role of gut microbial metabolites in this association. This study aimed to investigate the associations of the gut microbiota and fecal metabolome with intelligence quotient (IQ) in preschoolers. Methods: The 16 S rRNA sequencing and widely targeted metabolomics were applied to analyze the gut microbiota and fecal metabolites of 150 children aged 3–6 years. The Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) was used to assess the cognitive competence. Results: The observed species index, gut microbiome health index, and microbial dysbiosis index presented significant differences between children with full-scale IQ (FSIQ) below the borderline (G1) and those with average or above-average (all P < 0.05). The abundance of Acinetobacter, Blautia, Faecalibacterium, Prevotella_9, Subdoligranulum, Collinsella, Dialister, Holdemanella, and Methanobrevibacter was significantly associated with preschooler's WPPSI-IV scores (P < 0.05). In all, 87 differential metabolites were identified, mainly including amino acid and its metabolites, fatty acyl, and benzene and substituted derivatives. The differential fecal metabolites carnitine C20:1-OH, 4-hydroxydebrisoquine, pantothenol, creatine, N,N-bis(2-hydroxyethyl) dodecanamide, FFA(20:5), zerumbone, (R)-(-)-2-phenylpropionic acid, M-toluene acetic acid, trans-cinnamaldehyde, isonicotinic acid, val-arg, traumatin, and 3-methyl-4-hydroxybenzaldehyde were significantly associated with the preschooler's WPPSI-IV scores (P < 0.05). The combination of Acinetobacter, Isonicotinic acid, and 3-methyl-4-hydroxybenzaldehydenine may demonstrate increased discriminatory power for preschoolers in G1. Conclusion: This study reveals a potential association between gut microbiome and metabolites with IQ in preschoolers, providing new directions for future research and practical applications. However, due to limitations such as the small sample size, unclear causality, and the complexity of metabolites, more validation studies are still needed to further elucidate the mechanisms and stability of these associations. [ABSTRACT FROM AUTHOR]

Background: It is common knowledge that people's intestinal microbiota is significantly influenced by the external environment. Although the Antarctic continent has been discovered for nearly 200 years, it is still unclear how this environment affects the human intestinal microbiota, especially that of the Chinese Han population. Methods: Twelve explorers underwent a one-year Antarctic deployment from December 2017 to December 2018. The gut microbiota and clinical indexes at five time points, including two months (T1), five months (T2), eight months (T3), 11 months (T4) of residence in Antarctica and 7 months after returning to China (T5), were investigated. Results: The intestinal microbiota of the participants was changed after one-year Antarctic deployment even after they left Antarctica. For the microbiota tested after returning to China (T5), the amount of Citrobacter, Akkermansia and conditional pathogens such as Escherichia-Shigella increased significantly (P < 0.05). The concentration of the major biochemical indicators in the serum exhibited an increasing trend before T3, and decreased significantly at T4. When tested again at T5, most of the serum concentrations increased, only 5-hydroxytryptamine was significantly decreased. Spearman correlation analysis showed the change in the relative abundance of Anaerotruncus was negatively associated with the changes in the concentration of total thyroxine, alanine transaminase, γ-glutamyl transpeptidase, serum cystatin C and apolipoprotein A1. The relative abundance change in Citrobacter was positively associated with the change in the concentration of uric acid. Conclusion: By objectively analyzing the influence of the Antarctic environment on the change of intestinal microbiota, we were able to provide theoretical support for subsequent Antarctic related research. [ABSTRACT FROM AUTHOR]

Human gut microbiomes (microbiotas) are highly individualistic in taxonomic composition but nevertheless are functionally similar. Thus, collectively, they comprise a "metacommunity." In ecological terminology, the assembly of human gut microbiomes is influenced by four processes: selection, speciation, drift, and dispersal. As a result of fortuitous events associated with these processes, individual microbiomes are taxonomically "tailor-made" for each host. However, functionally they are "off-the-shelf" because of similar functional outputs resulting from metabolic redundancy developed in host-microbe symbiosis. Because of this, future microbiological and molecular studies of microbiomes should emphasize the metabolic interplay that drives the human gut metacommunity and that results in these similar functional outputs. This knowledge will support the development of remedies for specific functional dysbioses and hence provide practical examples of precision medicine. [ABSTRACT FROM AUTHOR]

Background: This prospective study aims to investigate the comparative effects of clear aligners (CA) and traditional removable appliances (RA) on the cariogenic risk of patients in mixed dentition, focusing on the oral microbiome. Methods: 25 children were included and assigned into CA and RA groups. Supragingival plaque and saliva samples were collected, and clinical parameters including Decay-missing-filled teeth index (DMFT), Plaque Index (PI) and Gorelick Index (GI) were recorded before treatment (T0) and after 6-month follow-up (T1). DNA was extracted from supragingival plaque and saliva and analyzed via 16S rDNA gene sequencing. Results: Clinical parameters showed no statistically significant difference between groups at each time point or within group over time (p > 0.05). In both RA and CA groups, saliva exhibited significantly higher alpha diversity compared to supragingival plaque at T1, as indicated by the significantly higher Chao1 and Shannon indexes (p < 0.05). Regarding beta diversity, significant difference was observed in saliva and supragingival plaque samples between T0 and T1 within group RA (p < 0.05, Adonis), whereas no such significance was noted in the CA group (p > 0.05, Adonis). At the genus level, Lactobacillus exhibited a statistically significant increase in saliva and supragingival plaque of group RA from T0 to T1 (p < 0.05), and an increasing trend in the group CA without statistical significance (p > 0.05). At T1, Lactobacillus levels were comparable between groups, whereas species-level analysis revealed distinct cariogenic species. Conclusion: Both clear aligners and traditional removable appliances resulted in elevated cariogenic risk of patients in mixed dentition at the microbial level. Distinct alterations in cariogenic species were observed to be induced by various orthodontic appliances. [ABSTRACT FROM AUTHOR]

Through complex interactions with the host's immune and physiological systems, gut bacteria play a critical role as etiological agents in a variety of human diseases, having an impact that extends beyond their mere presence and affects the onset, progression, and severity of the disease. Gaining a comprehensive understanding of these microbial interactions is crucial to improving our understanding of disease pathogenesis and creating tailored treatment methods. Correcting microbial imbalances may open new avenues for disease prevention and treatment approaches, according to preliminary data. The gut microbiota exerts an integral part in the pathogenesis of numerous health conditions, including metabolic, neurological, renal, cardiovascular, and gastrointestinal problems as well as COVID-19, according to recent studies. The crucial significance of the microbiome in disease pathogenesis is highlighted by this role, which is comparable to that of hereditary variables. This review investigates the etiological contributions of the gut microbiome to human diseases, its interactions with the host, and the development of prospective therapeutic approaches. To fully harness the benefits of gut microbiome dynamics for improving human health, future research should address existing methodological challenges and deepen our knowledge of microbial interactions. [ABSTRACT FROM AUTHOR]

Background: Bacterial pathogens such as Staphylococcus aureus colonize body surfaces of part of the human population, which represents a critical risk factor for skin disorders and invasive infections. However, such pathogens do not belong to the human core microbiomes. Beneficial commensal bacteria can often prevent the invasion and persistence of such pathogens by using molecular strategies that are only superficially understood. We recently reported that the commensal bacterium Staphylococcus lugdunensis produces the novel antibiotic lugdunin, which eradicates S. aureus from the nasal microbiomes of hospitalized patients. However, it has remained unclear if S. lugdunensis may affect S. aureus carriage in the general population and which external factors might promote S. lugdunensis carriage to enhance its S. aureus-eliminating capacity. Results: We could cultivate S. lugdunensis from the noses of 6.3% of healthy human volunteers. In addition, S. lugdunensis DNA could be identified in metagenomes of many culture-negative nasal samples indicating that cultivation success depends on a specific bacterial threshold density. Healthy S. lugdunensis carriers had a 5.2-fold lower propensity to be colonized by S. aureus indicating that lugdunin can eliminate S. aureus also in healthy humans. S. lugdunensis-positive microbiomes were dominated by either Staphylococcus epidermidis, Corynebacterium species, or Dolosigranulum pigrum. These and further bacterial commensals, whose abundance was positively associated with S. lugdunensis, promoted S. lugdunensis growth in co-culture. Such mutualistic interactions depended on the production of iron-scavenging siderophores by supportive commensals and on the capacity of S. lugdunensis to import siderophores. EJt4aqYa_PFzdC4ihACHg3 Video Abstract Conclusions: These findings underscore the importance of microbiome homeostasis for eliminating pathogen colonization. Elucidating mechanisms that drive microbiome interactions will become crucial for microbiome-precision editing approaches. [ABSTRACT FROM AUTHOR]

Background: Mouth breathing (MB), a risk factor of oral dysbiosis and halitosis, is linked with craniofacial anomalies and pediatric obstructive sleep apnea. Here, we aimed to analyze tongue microbiota in children from the perspective of their breathing pattern before/during orthodontic treatment. Methods: This prospective case–control study included 30 children with orthodontic anomalies, 15 with MB and 15 with nasal breathing (NB), matched by age, sex, and body mass index. All underwent orthodontic examination and sleep apnea monitoring. Tongue swabs were collected before starting (timepoint M0) and approx. six months into the orthodontic therapy (timepoint M6). Oral candidas and bacteriome were analyzed using mass spectrometry technique and 16S rRNA sequencing, respectively. Results: MB was associated with higher apnea–hypopnea index. At M0, oral candidas were equally present in both groups. At M6, Candida sp. were found in six children with MB but in none with NB. No significant differences in bacterial diversity were observed between groups and timepoints. However, presence/relative abundance of genus Solobacterium was higher in children with MB than NB at M0. Conclusions: Significant links between MB and the presence of genus Solobacterium (M0) as well as Candida sp. (M6) were found in children with orthodontic anomalies, highlighting the risk of halitosis in them. [ABSTRACT FROM AUTHOR]

Sewage metagenomics has risen to prominence in urban population surveillance of pathogens and antimicrobial resistance (AMR). Unknown species with similarity to known genomes cause database bias in reference-based metagenomics. To improve surveillance, we seek to recover sewage genomes and develop a quantification and correlation workflow for these genomes and AMR over time. We use longitudinal sewage sampling in seven treatment plants from five major European cities to explore the utility of catch-all sequencing of these population-level samples. Using metagenomic assembly methods, we recover 2332 metagenome-assembled genomes (MAGs) from prokaryotic species, 1334 of which were previously undescribed. These genomes account for ~69% of sequenced DNA and provide insight into sewage microbial dynamics. Rotterdam (Netherlands) and Copenhagen (Denmark) show strong seasonal microbial community shifts, while Bologna, Rome, (Italy) and Budapest (Hungary) have occasional blooms of Pseudomonas-dominated communities, accounting for up to ~95% of sample DNA. Seasonal shifts and blooms present challenges for effective sewage surveillance. We find that bacteria of known shared origin, like human gut microbiota, form communities, suggesting the potential for source-attributing novel species and their ARGs through network community analysis. This could significantly improve AMR tracking in urban environments. In this study, the authors use metagenomics to analyze sewage samples from five European cities over time and report enhanced detection of rare taxa through combined assembly methods, significant seasonal and geographical microbiome variations, and the potential to attribute microbial sequences to specific sources. [ABSTRACT FROM AUTHOR]

Bacteriophages are influential within the human gut microbiota, yet they remain understudied relative to bacteria. This is a limitation of studies on fecal microbiota transplantation (FMT) where bacteriophages likely influence outcome. Here, using metagenomics, we profile phage populations - the phageome - in individuals recruited into two double-blind randomized trials of FMT in ulcerative colitis. We leverage the trial designs to observe that phage populations behave similarly to bacterial populations, showing temporal stability in health, dysbiosis in active disease, modulation by antibiotic treatment and by FMT. We identify a donor bacteriophage putatively associated with disease remission, which on genomic analysis was found integrated in a bacterium classified to Oscillospiraceae, previously isolated from a centenarian and predicted to produce vitamin B complex except B12. Our study provides an in-depth assessment of phage populations during different states and suggests that bacteriophage tracking has utility in identifying determinants of disease activity and resolution. Here, the authors profile the gut phageome of individuals recruited into two double-blind randomized trials of Fecal Microbial Transplantation for ulcerative colitis, showing that phage communities are stable in health, dysbiotic in ulcerative colitis, modulated by antibiotics and by fecal transplants, with one Oscillospiraceae phage being associated with disease remission. [ABSTRACT FROM AUTHOR]

Objectives: Many studies have confirmed that antibacterial agents can disrupt the human gut microbiota. In China, Tanreqing injection (TRQ) is a drug with antibacterial activity that is widely used in the treatment of respiratory infections. However, its specific influence on gut microbiota remains unclear. This study aimed to investigate the effect of TRQ on the gut microbiota of healthy volunteers. Methods: Twelve healthy adults received 20 ml of TRQ intravenously daily for 7 consecutive days. At six timepoints (Pre, on D1, D3, D5, D7 and follow-up visit) fecal samples were collected and analyzed using 16S rRNA gene sequencing. Results: Eleven people were included in the analysis finally. TRQ did not significantly alter gut microbiota diversity or richness (Shannon and Simpson and Chao1 index) in healthy people during the intervention. Gut microbial structure was stable (weighted and unweighted Unifrac). Using a machine learning method based on PLS-DA analysis, the separation trend on D7 at the genus level was found, returning to baseline two days after discontinuation. The abundance of major genus fluctuated on D7 compared with that prior to treatment, including an increase of unclassified_f_Enterobacteriaceae (13.0611%), a decrease of Bifidobacterium and Escherichia-Shigella (6.887%, 10.487%). Functional prediction analysis did not reveal any significant difference. Conclusions: Our study showed short-term use of TRQ at conventional doses may not cause perturbations to the gut microbiota in healthy adults. This finding provides some useful information for the safe use of TRQ in the treatment of respiratory infections. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck cancers (HNCs) represent 4–5% of all malignancies globally. Salivary metabolites, as metabolic intermediates and signalling molecules, are gaining attention as diagnostic biomarkers for several diseases, including HNC; however, the metabolites' role in cancer treatment outcomes and oral side effects remains underexplored. Current studies focus on the oral microbiome's significance in promoting a pro-inflammatory environment that facilitates tumour development and invasion. Specific microorganisms and their metabolites influence chemotherapy efficacy through several mechanisms. Radiotherapy (RT), a standard HNC treatment, can modify the oral microbiota and salivary metabolite profiles, leading to a wide range of side effects. To reduce oral complications, intensity-modulated radiotherapy (IMRT) was developed; however, cancer survivors often experience a reduced quality of life. This review highlights the microbial and host interactions affecting salivary metabolites and their implications for cancer treatment and patient outcomes. Head and neck cancers (HNCs) are the seventh most common cancer worldwide, accounting for 4–5% of all malignancies. Salivary metabolites, which serve as key metabolic intermediates and cell-signalling molecules, are emerging as potential diagnostic biomarkers for HNC. While current research has largely concentrated on these metabolites as biomarkers, a critical gap remains in understanding their fluctuations before and after treatment, as well as their involvement in oral side effects. Recent studies emphasise the role of the oral microbiome and its metabolic activity in cancer progression and treatment efficacy by bacterial metabolites and virulence factors. Oral bacteria, such as P. gingivalis and F. nucleatum, contribute to a pro-inflammatory environment that promotes tumour growth. Additionally, F. nucleatum enhances its virulence through flagellar assembly and iron transport mechanisms, facilitating tumour invasion and survival. Moreover, alterations in the oral microbiome can influence chemotherapy efficacy and toxicity through the microbiota–host irinotecan axis, highlighting the complex interplay between microbial communities and therapeutic outcomes. Salivary metabolite profiles are influenced by factors such as gender, methods, and patient habits like smoking—a major risk factor for HNC. Radiotherapy (RT), a key treatment for HNC, often causes side effects such as xerostomia, oral mucositis, and swallowing difficulties which impact survivors' quality of life. Intensity-modulated radiotherapy (IMRT) aims to improve treatment outcomes and minimise side effects but can still lead to significant salivary gland dysfunction and associated complications. This review underscores the microbial and host interactions affecting salivary metabolites and their implications for cancer treatment and patient outcomes. [ABSTRACT FROM AUTHOR]