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Claudio Costantini Department of Medicine and Surgery, University of Perugia, Perugia, Italy

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Mirco Dindo Department of Medicine and Surgery, University of Perugia, Perugia, Italy

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Marilena Pariano Department of Medicine and Surgery, University of Perugia, Perugia, Italy

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Claudia Stincardini Department of Medicine and Surgery, University of Perugia, Perugia, Italy

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Silvia Grottelli Department of Medicine and Surgery, University of Perugia, Perugia, Italy

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Leonardo Gatticchi Department of Medicine and Surgery, University of Perugia, Perugia, Italy

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Giorgia Mandrile Medical Genetics Unit and Thalassemia Center, San Luigi University Hospital, University of Torino, Orbassano, Italy

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Barbara Cellini Department of Medicine and Surgery, University of Perugia, Perugia, Italy

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Luigina Romani Department of Medicine and Surgery, University of Perugia, Perugia, Italy
University San Raffaele and Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele, Rome, Italy

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Kaushik Karambelkar Data and Decision Sciences, Tata Consultancy Services Ltd., Thane, Maharashtra, India

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Mayank Baranwal Data and Decision Sciences, Tata Consultancy Services Ltd., Thane, Maharashtra, India
Systems and Control Engineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra, India

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Graphical abstract

Abstract

Objective

Preterm birth (PTB) is one of the leading issues concerning infant health and is a problem that plagues all parts of the world. Vaginal microbial communities have recently garnered attention in the context of PTB; however, the vaginal microbiome varies greatly from individual to individual, and this variation is more pronounced in racially, ethnically, and geographically diverse populations. Additionally, microbial communities have been reported to evolve during the duration of the pregnancy, and capturing such a signature may require higher, more complex modeling paradigms. In this study, we develop a neural controlled differential equation (CDE)-based framework for identifying early PTBs in racially diverse cohorts from irregularly sampled vaginal microbial abundance data.

Methods

We obtained relative abundances of microbial species within vaginal microbiota using 16S rRNA sequences obtained from vaginal swabs at various stages of pregnancy. We employed a recently introduced deep learning paradigm known as ‘neural CDEs’ to predict PTBs. This method, previously unexplored, analyzes irregularly sampled microbial abundance profiles in a time-series format.

Results

Our framework is able to identify signatures in the temporally evolving vaginal microbiome during trimester 2 and can predict incidences of PTB (mean test set ROC–AUC = 0.81, accuracy = 0.75, F1 score = 0.71) significantly better than traditional ML classifiers, thus enabling effective early-stage PTB risk assessment.

Conclusion and significance

Our method is able to differentiate between term and preterm outcomes with a substantial accuracy, despite being trained using irregularly sampled microbial abundance profiles, thus overcoming the limitations of traditional time-series modeling methods.

Open access
Sweta Ghosh Department of Microbiology and Immunology, Brown Cancer Center, Center for Microbiomics, Inflammation and Pathogenicity, University of Louisville, Louisville, Kentucky, United States of America

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Syam P Nukavarapu Department of Biomedical Engineering and Department of Materials Science & Engineering, University of Connecticut, Storrs, Connecticut, United States of America

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Venkatakrishna Rao Jala Department of Microbiology and Immunology, Brown Cancer Center, Center for Microbiomics, Inflammation and Pathogenicity, University of Louisville, Louisville, Kentucky, United States of America

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Exposure to environmental pollutants such as heavy metals lead to significant damage in intestinal epithelial barrier, loss of microbial and immune homeostasis. The intestinal epithelial barrier protects and regulates the responses against several endogenous and exogenous factors including inflammatory cytokines, pathogens, toxins, and pollutants. Intestinal epithelial barrier dysfunction, immune dysregulation and microbial dysbiosis are associated with several gastrointestinal (GI)-related disorders including inflammatory bowel disease (IBD). The mechanisms and consequences of exposure to environmental toxins on gut barrier function and mucosal immune system are not fully understood. This review explores some of the recent findings of heavy metals and their effect on intestinal barrier function, microbiota, and their contributions to human health and pathogenesis of GI-related disorders such as IBD.

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Nadja Paeslack Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg-University Mainz, Germany

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Christoph Reinhardt Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg-University Mainz, Germany
German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany

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The commensal microbiota resides in a mutualistic relationship within the mammalian gut. It significantly influences the formation of capillary networks in the small intestine, not only during development but also in adulthood. Mucosal capillaries in small intestinal villus structures play a critical role for the uptake of dietary nutrients and immune regulation. Emerging studies have elucidated how the composition of gut microbiota can influence not only postnatal gut development regarding immune tolerance, nutrient absorption, and morphology but also the development and maintenance of blood and lymphatic capillaries within the small intestine. In particular, the analysis of gnotobiotic mouse models affirmed the importance of the gut microbiota, or even only single gut bacteria, in the remodeling of the small intestinal capillaries. Here, different epithelial-to-endothelial cross talk pathways, e.g. Paneth cell-derived signals, Toll-like receptor signaling, or tissue factor–protease activated receptor-1 signaling, have been reported to affect intestinal villus vascular remodeling in a microbiota-dependent fashion. In this review article, we will provide a comprehensive overview on the relevant microbiota–host interaction pathways, which have been revealed to influence angiogenesis and vascular remodeling in the small intestine.

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Elizabeth A Coler Department of Chemistry, University of Connecticut, Storrs, Connecticut, USA

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Wanxuan Chen Department of Chemistry, University of Connecticut, Storrs, Connecticut, USA

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Alexey V Melnik Department of Chemistry, University of Connecticut, Storrs, Connecticut, USA
Arome Science Inc., Farmington, Connecticut, USA

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James T Morton Gutz Analytics LLC, Boulder, Colorado, USA

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Alexander A Aksenov Department of Chemistry, University of Connecticut, Storrs, Connecticut, USA
Arome Science Inc., Farmington, Connecticut, USA

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Artificial intelligence (AI) is rapidly revolutionizing our daily lives, as it automates mundane tasks, enhances productivity, and transforms how we interact with technology. We believe it is inevitable that AI will soon become a crucial tool in common research practices, from data analysis to writing papers. Here we explore how this transition is occurring in the field of mass spectrometry-based metabolomics, a rapidly growing area of science. Metabolomics focuses on studying small molecules in biological systems, offering valuable insights into metabolic processes and their impact on health, diseases, and physiological conditions. With the remarkable advancements in sequencing technologies and the exploration of the microbiome, the combination of sequencing and metabolomics presents profound opportunities to understand biological complexity. Incorporating AI is promising to unlock new possibilities for expanding the realms of scientific discoveries. In this review we specifically focus on the current trends in the application of AI in metabolomics research. Existing practices are examined and a perspective on future directions for integrating AI into metabolomics research is presented.

Open access
Morgan A Maly Center for Conservation Genomics, Smithsonian National Zoo and Conservation Biology Institute, Washington, DC, USA
Department of Animal Care Science, Smithsonian National Zoo and Conservation Biology Institute, Front Royal, Virginia, USA
Department of Biological Sciences, College of Sciences, North Carolina State University, Raleigh, North Carolina, USA
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA

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Adrienne E Crosier Department of Animal Care Science, Smithsonian National Zoo and Conservation Biology Institute, Front Royal, Virginia, USA

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Mia M Keady Center for Conservation Genomics, Smithsonian National Zoo and Conservation Biology Institute, Washington, DC, USA
Nelson Institute for Environmental Studies, University of Wisconsin-Madison, Madison, Wisconsin, USA

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Reade B Roberts Department of Biological Sciences, College of Sciences, North Carolina State University, Raleigh, North Carolina, USA

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Matthew Breen Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA

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Carly R Muletz-Wolz Center for Conservation Genomics, Smithsonian National Zoo and Conservation Biology Institute, Washington, DC, USA

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Objective

Gut health and its relationship to gut microbiota is an important consideration in the care and well-being of managed endangered species, such as the cheetah (Acinonyx jubatus). Non-invasive fecal sampling as a proxy for gut microbiota is preferred and collecting fresh fecal samples is the current gold standard. Unfortunately, even in managed facilities, collecting fresh samples from difficult to observe or dangerous animals is challenging. Therefore, we conducted a study to determine the terminal collection timepoint for fecal microbial studies in the cheetah.

Methods

We longitudinally sampled eight freshly deposited fecals every 24 h for 5 days and assessed bacterial relative abundance, diversity, and composition changes over time.

Results

Our data indicated that fecal samples up to 24 h post defecation provided accurate representations of the fresh fecal microbiome. After 24 h, major changes in community composition began to occur. By 72 h, individual cheetah fecal microbiota signatures were lost.

Conclusion

Our findings suggest that cheetah fecal samples should be collected within 24 h of defecation in humid environments, especially if precipitation occurs, in order to provide a more biologically accurate representation of the gut microbiome, and we provide visual characteristics that can aid researchers in approximating time since defecation.

Significance statement

Data from this study provides guidelines for researchers investigating cheetah and other large felids and carnivores where the ability to collect fresh fecal deposits is limited.

Open access
Paige Buffington Department of Physician Assistant Studies, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

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Alexia M Sebghati Department of Physician Assistant Studies, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

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Kasey B Stewart Department of Physician Assistant Studies, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

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Samantha Lawson Department of Physician Assistant Studies, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

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Oleg Karaduta Department of Physician Assistant Studies, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

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Objective

This study aims to evaluate the impact of cesarean section delivery on the neonatal intestinal microflora compared to vaginal deliveries.

Design

A mini-review.

Methods

A comprehensive search strategy was implemented, primarily using PubMed, to identify relevant studies published in English within the past 10 years. Selected studies were appraised by three independent reviewers using JBI critical appraisal and data extraction forms. Four articles were included in the analysis, encompassing systematic reviews and a retrospective cohort study. Primary and secondary outcome data were combined across these studies.

Results

Selected studies revealed consistent trends in bacterial colonization differences between cesarean and vaginal deliveries. Vaginally delivered infants exhibited higher populations of beneficial bacteria such as Bifidobacterium, Lactobacillus, and Bacteroides. Cesarean-delivered infants, on the other hand, showed greater colonization of Enterococcus, Klebsiella, Clostridium, Staphylococcus, Streptococcus, and Corynebacterium. Statistically significant differences were observed in two studies. All articles explored the potential health implications of these microbiome differences, with associations found between cesarean deliveries and various health outcomes.

Conclusion

This review demonstrates that cesarean section delivery influences the composition of the neonatal gut microbiota. The presence of certain bacterial species more prevalent in vaginally delivered infants, such as Bifidobacterium, is associated with improved infant health, while species found in cesarean-delivered infants, such as Clostridium, increase the risk of certain infections. Recognizing the increased health risks for cesarean-born infants enables clinicians to implement early screening, treatment, or prevention strategies, potentially reducing future morbidity and mortality.

Open access
Josey Muske Mayo Graduate School of Biomedical Sciences, Mayo Clinic Rochester, Minnesota, USA
Department of Immunology, Mayo Clinic Rochester, Minnesota, USA

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Kathryn Knoop Department of Immunology, Mayo Clinic Rochester, Minnesota, USA
Department of Pediatrics, Mayo Clinic Rochester, Minnesota, USA

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The health of the intestinal microbiota impacts tolerance at homeostasis and the strength of the inflammation response during acute bloodstream infections. A complete understanding of the feedback loop between systemic inflammation and dysregulation of the gut microbiota is necessary for inflammation management. Here we will review the many ways in which the microbiota can influence the systemic pro-inflammatory response. Short-chain fatty acids, produced through the microbial metabolism of dietary fibers, can suppress inflammation systemically; in the absence of a balanced diet or disruption of the microbiota through antibiotics, there is disrupted metabolite production, leading to systemic inflammation. Dysbiosis or inflammation in the intestines can lead to a breakdown of the sturdy intestinal–epithelial barrier. When this barrier is perturbed, immunogenic lipopolysaccharides or extracellular vesicles enter the bloodstream and induce excessive inflammation. Necessary clinical treatments, such as antifungals or antibacterials, induce microbiota dysregulation and thus increased risk of endotoxemia; though probiotics may aid in improving the microbiota health and have been shown to deflate inflammation during sepsis. Within this complicated relationship: What is in control, the dysbiotic microbiota or the systemic inflammation?

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Simran Kaur Cheema School of Biological Sciences, Institute for Global Food Security, Queen’s University Belfast, UK

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Ranran Li School of Biological Sciences, Institute for Global Food Security, Queen’s University Belfast, UK

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Simon J S Cameron School of Biological Sciences, Institute for Global Food Security, Queen’s University Belfast, UK

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For almost a century, it has been accepted that human milk contains viable microbial cells. However, for a considerable amount of this period, it was believed that they were the result of exogenous contamination, primarily from the skin or non-sterile handling. Early work using culture-dependent methods, supported by molecular profiling, however, identified the presence of lactic acid bacteria from an endogenous origin. This provided evidence that the human milk microbiota consisted of microorganisms that were not found solely on the skin surface and therefore could not result from contamination. Through the advent of next-generation sequencing, the field of microbiota research has caused a paradigm shift away from a typical focus on the presence of pathogenic microorganisms in human milk. This had led to a broad appreciation that the human milk microbiota consists of several hundred species of non-pathogenic commensal microbes – with many anaerobic microbial taxons being found only in the gastrointestinal tract outside of human milk. Nevertheless, as our appreciation of the complexity and diversity of the human milk microbiota has improved, many questions relating to the functional basis of host–microbiota interactions in the newborn infant’s gastrointestinal tract remain outstanding. To address these, mechanistic studies will be required in which the utilisation of isolated microorganisms will be essential. As such, a return to culture-dependent methods in the new paradigm of culturomics will be required. In this review, we bring together the current understanding of the human milk microbiota and how culturomics could play a fundamental role in furthering our understanding.

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Muhammad Hassan Saeed Intestinal Microbiome, School of Life Sciences, ZIEL – Institute for Food & Health, Technical University of Munich, Freising, Germany

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Lindsay J Hall Intestinal Microbiome, School of Life Sciences, ZIEL – Institute for Food & Health, Technical University of Munich, Freising, Germany
Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, UK

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The early-life microbiota is an ‘immature’ and highly dynamic microbial ecosystem, which is central to infant health. Both perinatal and postnatal factors can impact the gut microbiota, with antibiotics proposed to cause short and longer-term disturbances. Antibiotics not only impact microbial community composition but also contribute to the overall antibiotic resistance profile, i.e. the ‘resistome’, and they may also enhance carriage of multi-drug-resistant bacteria. Given high antibiotic prescription practices in pregnant women and newborns this also contributes to the global threat of antimicrobial resistance. This review summarises the current literature on antibiotic usage and how this may impact the developing gut microbiota during early-life, including the influence of horizontal gene transfer on contributions to pathogenicity and resistance of gut bacteria. We also focus on Enterococcus spp. given their high levels in infants and their link with opportunistic infections that are a significant cause of morbidity and mortality during early-life. Finally, a perspective on the importance to antibiotic stewardship, and harnessing the microbiota itself for anti-infection therapies for reducing antibiotic usage are also covered.

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