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Bibliography on: Human Microbiome

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ESP: PubMed Auto Bibliography 20 Dec 2024 at 01:52 Created: 

Human Microbiome

The human microbiome is the set of all microbes that live on or in humans. Together, a human body and its associated microbiomes constitute a human holobiont. Although a human holobiont is mostly mammal by weight, by cell count it is mostly microbial. The number of microbial genes in the associated microbiomes far outnumber the number of human genes in the human genome. Just as humans (and other multicellular eukaryotes) evolved in the constant presence of gravity, so they also evolved in the constant presence of microbes. Consequently, nearly every aspect of human biology has evolved to deal with, and to take advantage of, the existence of associated microbiota. In some cases, the absence of a "normal microbiome" can cause disease, which can be treated by the transplant of a correct microbiome from a healthy donor. For example, fecal transplants are an effective treatment for chronic diarrhea from over abundant Clostridium difficile bacteria in the gut.

Created with PubMed® Query: "human microbiome" NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

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RevDate: 2024-12-19

Evans SE, Valentine ME, Gallimore F, et al (2024)

Perturbations in the Gut Microbiome of C57BL/6J Mice by the Sobriety Aid Antabuse® (Disulfiram).

Journal of applied microbiology pii:7929021 [Epub ahead of print].

AIMS: Disulfiram (Antabuse®) is an oral alcohol sobriety medication that exhibits antimicrobial activity against Gram-positive facultative anaerobes. The aims of this study were to measure the antimicrobial activity against anaerobic bacteria of the gut human microbiome and establish the extent that disulfiram alters the microbial composition of the ileum, cecum, and feces using C57BL/6 mice.

METHODS AND RESULTS: Antimicrobial susceptibility testing by the microdilution method revealed that disulfiram inhibits the in vitro growth of gut anaerobic species of Bacteroides, Clostridium, Peptostreptococcus, and Porphyromonas. Differential sequencing of 16S rRNA isolated from the ileum, cecum, and feces contents of treated vs. untreated mice showed disulfiram enriches the Gram-negative enteric population. In female mice, the enrichment was greatest in the ileum whereas the feces composition in male mice was the most heavily altered.

CONCLUSIONS: Daily administration of oral disulfiram depletes the enteric Gram-positive anaerobe population as predicted by the MIC data for isolates from the human gut microbiota.

RevDate: 2024-12-19

Lei Y, Li M, Zhang H, et al (2024)

Comparative analysis of the human microbiome from four different regions of China and machine learning-based geographical inference.

mSphere [Epub ahead of print].

The human microbiome, the community of microorganisms that reside on and inside the human body, is critically important for health and disease. However, it is influenced by various factors and may vary among individuals residing in distinct geographic regions. In this study, 220 samples, consisting of sterile swabs from palmar skin and oral and nasal cavities were collected from Chinese Han individuals living in Shanghai, Chifeng, Kunming, and Urumqi, representing the geographic regions of east, northeast, southwest, and northwest China. The full-length 16S rRNA gene of the microbiota in each sample was sequenced using the PacBio single-molecule real-time sequencing platform, followed by clustering the sequences into operational taxonomic units (OTUs). The analysis revealed significant differences in microbial communities among the four regions. Cutibacterium was the most abundant bacterium in palmar samples from Shanghai and Kunming, Psychrobacter in Chifeng samples, and Psychrobacillus in Urumqi samples. Additionally, Streptococcus and Staphylococcus were the dominant bacteria in the oral and nasal cavities. Individuals from the four regions could be distinguished and predicted based on a model constructed using the random forest algorithm, with the predictive effect of palmar microbiota being better than that of oral and nasal cavities. The prediction accuracy using hypervariable regions (V3-V4 and V4-V5) was comparable with that of using the entire 16S rRNA. Overall, our study highlights the distinctiveness of the human microbiome in individuals living in these four regions. Furthermore, the microbiome can serve as a biomarker for geographic origin inference, which has immense application value in forensic science.IMPORTANCEMicrobial communities in human hosts play a significant role in health and disease, varying in species, quantity, and composition due to factors such as gender, ethnicity, health status, lifestyle, and living environment. The characteristics of microbial composition at various body sites of individuals from different regions remain largely unexplored. This study utilized single-molecule real-time sequencing technology to detect the entire 16S rRNA gene of bacteria residing in the palmar skin, oral, and nasal cavities of Han individuals from four regions in China. The composition and structure of the bacteria at these three body sites were well characterized and found to differ regionally. The results elucidate the differences in bacterial communities colonizing these body sites across different regions and reveal the influence of geographical factors on human bacteria. These findings not only contribute to a deeper understanding of the diversity and geographical distribution of human bacteria but also enrich the microbiome data of the Asian population for further studies.

RevDate: 2024-12-19

Aluthge N, Adams S, Davila CA, et al (2024)

Gut microbiota profiling in injection drug users with and without HIV-1 infection in Puerto Rico.

Frontiers in microbiology, 15:1470037.

INTRODUCTION: The full extent of interactions between human immunodeficiency virus (HIV) infection, injection drug use, and the human microbiome is unclear. In this study, we examined the microbiomes of HIV-positive and HIV-negative individuals, both drug-injecting and non-injecting, to identify bacterial community changes in response to HIV and drug use. We utilized a well-established cohort of people who inject drugs in Puerto Rico, a region with historically high levels of injection drug use and an HIV incidence rate disproportionately associated with drug use.

METHODS: Using amplicon-based 16S rDNA sequencing, we identified amplicon sequence variants (ASVs) that demonstrated significant variations in the composition of microbial communities based on HIV status and drug use.

RESULTS AND DISCUSSION: Our findings indicate that the HIV-positive group exhibited a higher abundance of ASVs belonging to the genera Prevotella, Alloprevotella, Sutterella, Megasphaera, Fusobacterium, and Mitsuokella. However, Bifidobacteria and Lactobacillus ASVs were more abundant in injectors than in non-injectors. We examined the effect of drug use on the gut microbiome in both HIV-infected and non-infected patients, and found that multiple drug use significantly affected the microbial community composition. Analysis of differential of bacterial taxa revealed an enrichment of Bifidobacterium spp., Faecalibacterium spp., and Lactobacillus spp. in the multiple drug-injecting group. However, in the non-injecting group, Parabacteroides spp., Prevotella spp., Paraprevotella spp., Sutterella spp., and Lachnoclostridium spp. The presence of multiple drug-injecting groups was observed to be more prevalent. Our findings provide detailed insight into ASV-level changes in the microbiome in response to HIV and drug use, suggesting that the effect of HIV status and drug injection may have different effects on microbiome composition and in modulating gut bacterial populations.

RevDate: 2024-12-19
CmpDate: 2024-12-19

Rodriguez J, Cordaillat-Simmons M, Badalato N, et al (2024)

Microbiome testing in Europe: navigating analytical, ethical and regulatory challenges.

Microbiome, 12(1):258.

BACKGROUND: In recent years, human microbiome research has flourished and has drawn attention from both healthcare professionals and general consumers as the human microbiome is now recognized as having a significant influence on human health. This has led to the emergence of companies offering microbiome testing services. Some of these services are sold directly to the consumer via companies' websites or via medical laboratory websites.

METHODOLOGY: In order to provide an overview of the consumer experience proposed by these microbiome testing services, one single faecal sample was sent to six different companies (five based in Europe and one based in the USA). Two out of the six testing kits were commercialized by medical laboratories, but without any requirement for a medical prescription. The analyses and reports received were discussed with a panel of experts (21 experts from 8 countries) during an online workshop.

RESULTS: This workshop led to the identification of several limitations and challenges related to these kits, including over-promising messages from the companies, a lack of transparency in the methodology used for the analysis and a lack of reliability of the results. The experts considered the interpretations and recommendations provided in the different reports to be premature due to the lack of robust scientific evidence and the analyses associated with the reports to be of limited clinical utility. The experts also discussed the grey areas surrounding the regulatory status of these test kits, including their positioning in the European market. The experts recommended a distinction between regulatory requirements based on the intended use or purpose of the kit: on the one hand, test kits developed to satisfy consumer curiosity, with a clear mention of this objective, and no mention of any disease or risk of disease, and on the other hand, in vitro diagnostic (IVD) CE-marked test kits, which could go deeper into the analysis and interpretation of samples, as such a report would be intended for trained healthcare professionals.

CONCLUSIONS: Recommendations or actions, specific to the context of use of microbiome testing kits, are listed to improve the quality and the robustness of these test kits to meet expectations of end users (consumers, patients and healthcare professionals). The need for standardization, robust scientific evidence, qualification of microbiome-based biomarkers and a clear regulatory status in Europe are the main issues that will require attention in the near future to align laboratory development with societal needs and thus foster translation into daily health practice.

RevDate: 2024-12-18
CmpDate: 2024-12-18

Moore M, Whittington HD, Knickmeyer R, et al (2025)

Non-stochastic reassembly of a metabolically cohesive gut consortium shaped by N-acetyl-lactosamine-enriched fibers.

Gut microbes, 17(1):2440120.

Diet is one of the main factors shaping the human microbiome, yet our understanding of how specific dietary components influence microbial consortia assembly and subsequent stability in response to press disturbances - such as increasing resource availability (feeding rate) - is still incomplete. This study explores the reproducible re-assembly, metabolic interplay, and compositional stability within microbial consortia derived from pooled stool samples of three healthy infants. Using a single-step packed-bed reactor (PBR) system, we assessed the reassembly and metabolic output of consortia exposed to lactose, glucose, galacto-oligosaccharides (GOS), and humanized GOS (hGOS). Our findings reveal that complex carbohydrates, especially those containing low inclusion (~1.25 gL[-1]) components present in human milk, such as N-acetyl-lactosamine (LacNAc), promote taxonomic, and metabolic stability under varying feeding rates, as shown by diversity metrics and network analysis. Targeted metabolomics highlighted distinct metabolic responses to different carbohydrates: GOS was linked to increased lactate, lactose to propionate, sucrose to butyrate, and CO2, and the introduction of bile salts with GOS or hGOS resulted in butyrate reduction and increased hydrogen production. This study validates the use of single-step PBRs for reliably studying microbial consortium stability and functionality in response to nutritional press disturbances, offering insights into the dietary modulation of microbial consortia and their ecological dynamics.

RevDate: 2024-12-17
CmpDate: 2024-12-17

Ullah H, Hassan SHA, Yang Q, et al (2024)

Dynamic interaction of antibiotic resistance between plant microbiome and organic fertilizers: sources, dissemination, and health risks.

World journal of microbiology & biotechnology, 41(1):4.

Antibiotic resistance is a global health problem driven by the irrational use of antibiotics in different areas (such as agriculture, animal farming, and human healthcare). Sub-lethal concentrations of antibiotic residues impose selective pressure on environmental, plant-associated, and human microbiome leading to the emergence of antibiotic-resistant bacteria (ARB). This review summarizes all sources of antibiotic resistance in agricultural soils (including manure, sewage sludge, wastewater, hospitals/pharmaceutical industry, and bioinoculants). The factors (such as the physicochemical properties of soil, root exudates, concentration of antibiotic exposure, and heavy metals) that facilitate the transmission of resistance in plant microbiomes are discussed. Potential solutions for effective measures and control of antibiotic resistance in the environment are also hypothesized. Manure exhibits the highest antibiotics load, followed by hospital and municipal WW. Chlortetracycline, tetracycline, and sulfadiazine have the highest concentrations in the manure. Antibiotic resistance from organic fertilizers is transmitted to the plant microbiome via horizontal gene transfer (HGT). Plant microbiomes serve as transmission routes of ARB and ARGS to humans. The ingestion of ARB leads to human health risks (such as ineffectiveness of medication, increased morbidity, and mortality).

RevDate: 2024-12-17
CmpDate: 2024-12-17

Tsuchida S, Umemura H, Iizuka K, et al (2024)

Recent findings on metabolomics and the microbiome of oral bacteria involved in dental caries and periodontal disease.

World journal of microbiology & biotechnology, 41(1):11.

Periodontal disease is characterized by bacterial toxins within the oral biofilm surrounding the teeth, leading to gingivitis and the gradual dissolution of the alveolar bone, which supports the teeth. Notably, symptoms in the early stages of the disease are often absent. Similarly, dental caries occurs when oral bacteria metabolize dietary sugars, producing acids that dissolve tooth enamel and dentin. These bacteria are commonly present in the oral cavity of most individuals. Metabolomics, a relatively recent addition to the "omics" research landscape, involves the comprehensive analysis of metabolites in vivo to elucidate pathological mechanisms and accelerate drug discovery. Meanwhile, the term "microbiome" refers to the collection of microorganisms within a specific environmental niche or their collective genomes. The human microbiome plays a critical role in health and disease, influencing a wide array of physiological and pathological processes. Recent advances in microbiome research have identified numerous bacteria implicated in dental caries and periodontal disease. Additionally, studies have uncovered various pathogenic factors associated with these microorganisms. This review focuses on recent findings in metabolomics and the microbiome, specifically targeting oral bacteria linked to dental caries and periodontal disease. We acknowledge the limitation of relying exclusively on the MEDLINE database via PubMed, while excluding other sources such as gray literature, conference proceedings, and clinical practice guidelines.

RevDate: 2024-12-17

Chircop O, Jaggers C, Spiteri M, et al (2024)

DOXY do, or DOXY Don't? Syphilis and doxycycline post-exposure prophylaxis: A case report.

International journal of STD & AIDS [Epub ahead of print].

The resurgence of syphilis across Europe has led to a growing number of atypical cases, often characterised by varied symptoms that can delay diagnosis. We report the case of a young man who has sex with men (MSM), presenting with persistent headaches and swelling of the forehead suggestive of giant cell arteritis (GCA). Despite a recent negative syphilis test, further investigations confirmed the diagnosis of neurosyphilis. The patient had been using doxycycline post-exposure prophylaxis (DoxyPEP), which is suspected to have delayed the diagnosis by masking the typical antibody response. This case highlights concerns about DoxyPEP's impact on syphilis detection and disease progression. Further research is warranted to explore its effects on antimicrobial resistance, the human microbiome, and clinical outcomes.

RevDate: 2024-12-17

Jiang H, Miao X, Thairu MW, et al (2024)

Multimedia: multimodal mediation analysis of microbiome data.

Microbiology spectrum [Epub ahead of print].

UNLABELLED: Mediation analysis has emerged as a versatile tool for answering mechanistic questions in microbiome research because it provides a statistical framework for attributing treatment effects to alternative causal pathways. Using a series of linked regressions, this analysis quantifies how complementary data relate to one another and respond to treatments. Despite these advances, existing software's rigid assumptions often result in users viewing mediation analysis as a black box. We designed the multimedia R package to make advanced mediation analysis techniques accessible, ensuring that statistical components are interpretable and adaptable. The package provides a uniform interface to direct and indirect effect estimation, synthetic null hypothesis testing, bootstrap confidence interval construction, and sensitivity analysis, enabling experimentation with various mediator and outcome models while maintaining a simple overall workflow. The software includes modules for regularized linear, compositional, random forest, hierarchical, and hurdle modeling, making it well-suited to microbiome data. We illustrate the package through two case studies. The first re-analyzes a study of the microbiome and metabolome of Inflammatory Bowel Disease patients, uncovering potential mechanistic interactions between the microbiome and disease-associated metabolites, not found in the original study. The second analyzes new data about the influence of mindfulness practice on the microbiome. The mediation analysis highlights shifts in taxa previously associated with depression that cannot be explained indirectly by diet or sleep behaviors alone. A gallery of examples and further documentation can be found at https://go.wisc.edu/830110.

IMPORTANCE: Microbiome studies routinely gather complementary data to capture different aspects of a microbiome's response to a change, such as the introduction of a therapeutic. Mediation analysis clarifies the extent to which responses occur sequentially via mediators, thereby supporting causal, rather than purely descriptive, interpretation. Multimedia is a modular R package with close ties to the wider microbiome software ecosystem that makes statistically rigorous, flexible mediation analysis easily accessible, setting the stage for precise and causally informed microbiome engineering.

RevDate: 2024-12-17
CmpDate: 2024-12-17

Balla B, Illés A, Tobiás B, et al (2024)

The Role of the Vaginal and Endometrial Microbiomes in Infertility and Their Impact on Pregnancy Outcomes in Light of Recent Literature.

International journal of molecular sciences, 25(23): pii:ijms252313227.

The Human Microbiome Project (HMP), initiated in 2007, aimed to gather comprehensive knowledge to create a genetic and metabolic map of human-associated microorganisms and their contribution to physiological states and predisposition to certain diseases. Research has revealed that the human microbiome is highly diverse and exhibits significant interpersonal variability; consequently, its exact impact on health remains unclear. With the development of next-generation sequencing (NGS) technologies, the broad spectrum of microbial communities has been better characterized. The lower female genital tract, particularly the vagina, is colonized by various bacterial species, with Lactobacillus spp. predominating. The upper female genital tract, especially the uterus, was long considered sterile. However, recent studies have identified a distinct endometrial microbiome. A Lactobacillus-dominated microbiome of the female genital tract is associated with favorable reproductive outcomes, including higher success rates in natural conception and assisted reproductive technologies (ART). Conversely, microbial imbalances, or dysbiosis, marked by reduced Lactobacilli as well as an increased diversity and abundance of pathogenic species (e.g., Gardnerella vaginalis or Prevotella spp.), are linked to infertility, implantation failure, and pregnancy complications such as miscarriage and preterm birth. Dysbiosis can impair the vaginal or endometrial mucosal barrier and also trigger pro-inflammatory responses, disrupting essential reproductive processes like implantation. Despite growing evidence supporting the associations between the microbiome of the female genital tract and certain gynecological and obstetric conditions, clear microbial biomarkers have yet to be identified, and there is no consensus on the precise composition of a normal or healthy microbiome. The lack of standardized protocols and biomarkers limits the routine use of microbiome screening tests. Therefore, larger patient cohorts are needed to facilitate comparative studies and improve our understanding of the physiological microbiome profiles of the uterus and vagina, as well as how dysbiosis may influence clinical outcomes. Further research is required to refine diagnostic tools and develop personalized therapeutic strategies to improve fertility and pregnancy outcomes.

RevDate: 2024-12-17
CmpDate: 2024-12-17

Cominelli G, Lonati C, Pinto D, et al (2024)

Melatonin Attenuates Ferritinophagy/Ferroptosis by Acting on Autophagy in the Liver of an Autistic Mouse Model BTBR T[+]Itpr3[tf]/J.

International journal of molecular sciences, 25(23): pii:ijms252312598.

Autism spectrum disorders (ASDs) are a pool of neurodevelopment disorders in which social impairment is the main symptom. Presently, there are no definitive medications to cure the symptoms but the therapeutic strategies that are taken ameliorate them. The purpose of this study was to investigate the effects of melatonin (MLT) in treating ASDs using an autistic mouse model BTBR T[+]Itpr3[tf]/J (BTBR). We evaluated the hepatic cytoarchitecture and some markers of autophagy, ferritinophagy/ferroptosis, in BTBR mice treated and not-treated with MLT. The hepatic morphology and the autophagy and ferritinophagy/ferroptosis pathways were analyzed by histological, immunohistochemical, and Western blotting techniques. We studied p62 and microtubule-associated protein 1 light chain 3 B (LC3B) for evaluating the autophagy; nuclear receptor co-activator 4 (NCOA4) and long-chain-coenzyme synthase (ACSL4) for monitoring ferritinophagy/ferroptosis. The liver of BTBR mice revealed that the hepatocytes showed many cytoplasmic inclusions recognized as Mallory-Denk bodies (MDBs); the expression and levels of p62 and LC3B were downregulated, whereas ACSL4 and NCOA4 were upregulated, as compared to control animals. MLT administration to BTBR mice ameliorated liver damage and reduced the impairment of autophagy and ferritinophagy/ferroptosis. In conclusion, we observed that MLT alleviates liver damage in BTBR mice by improving the degradation of intracellular MDBs, promoting autophagy, and suppressing ferritinophagy/ferroptosis.

RevDate: 2024-12-17
CmpDate: 2024-12-17

Ouédraogo LO, Deng L, Ouattara CA, et al (2024)

Describing Biological Vulnerability in Small, Vulnerable Newborns in Urban Burkina Faso (DenBalo): Gut Microbiota, Immune System, and Breastmilk Assembly.

Nutrients, 16(23): pii:nu16234242.

Background: Small vulnerable newborns (SVNs), including those born preterm, small for gestational age, or with low birth weight, are at higher risk of neonatal mortality and long-term health complications. Early exposure to maternal vaginal microbiota and breastfeeding plays a critical role in the development of the neonatal microbiota and immune system, especially in low-resource settings like Burkina Faso, where neonatal mortality rates remain high. Objectives: The DenBalo study aims to investigate the role of maternal and neonatal factors, such as vaginal and gut microbiota, immune development, and early nutrition, in shaping health outcomes in SVNs and healthy infants. Methods: This prospective cohort observational study will recruit 141 mother-infant pairs (70 SVNs and 71 healthy controls) from four health centers in Bobo-Dioulasso, Burkina Faso. The mother-infant pairs will be followed for six months with anthropometric measurements and biospecimen collections, including blood, breast milk, saliva, stool, vaginal swabs, and placental biopsies. Multi-omics approaches, encompassing metagenomics, metabolomics, proteomics, and immune profiling, will be used to assess vaginal and gut microbiota composition and functionality, immune cell maturation, and cytokine levels at critical developmental stages. Conclusions: This study will generate comprehensive data on how microbiota, metabolomic, and proteomic profiles, along with immune system development, differ between SVNs and healthy infants. These findings will guide targeted interventions to improve neonatal health outcomes and reduce mortality, particularly in vulnerable populations.

RevDate: 2024-12-17
CmpDate: 2024-12-17

Kim S, Rahim MA, Tajdozian H, et al (2024)

Clinical Potential of Novel Microbial Therapeutic LP51 Based on Xerosis-Microbiome Index.

Cells, 13(23): pii:cells13232029.

Xerosis, characterized by dry, rough skin, causes discomfort and aesthetic concerns, necessitating effective treatment. Traditional treatments often show limited efficacy, prompting the need for innovative therapies. This study highlights the efficacy of microbiome therapeutic LP51, derived from a healthy vaginal microbiome, in improving xerosis. A double-blind clinical trial involving 43 subjects with dry inner arm skin compared the effects of a 2.9% LP51 extract formulation to a placebo over 4 weeks. The LP51 group exhibited a significant increase in stratum corneum hydration (10.0 A.U.) compared to the placebo group (4.8 A.U.) and a 21.4% decrease in transepidermal water loss (TEWL), whereas the placebo group showed no significant change. LP51 also demonstrated benefits in enhancing skin hydration, improving the skin barrier, and exhibited anti-atopic, anti-inflammatory, and antioxidant properties. Safety was confirmed through in vitro cytotoxicity tests. These effects are attributed to the microbiome-safe component in LP51 and its role in improving xerosis, reflected by an increase in the xerosis-microbiome index, defined by the Firmicutes/Actinobacteria ratio. These findings position microbiome therapeutic LP51 as a promising novel treatment for xerosis.

RevDate: 2024-12-17
CmpDate: 2024-12-17

Seo H, Kim S, Beck S, et al (2024)

Perspectives on Microbiome Therapeutics in Infectious Diseases: A Comprehensive Approach Beyond Immunology and Microbiology.

Cells, 13(23): pii:cells13232003.

Although global life expectancy has increased over the past 20 years due to advancements in managing infectious diseases, one-fifth of people still die from infections. In response to this ongoing threat, significant efforts are underway to develop vaccines and antimicrobial agents. However, pathogens evolve resistance mechanisms, complicating their control. The COVID-19 pandemic has underscored the limitations of focusing solely on the pathogen-killing strategies of immunology and microbiology to address complex, multisystemic infectious diseases. This highlights the urgent need for practical advancements, such as microbiome therapeutics, that address these limitations while complementing traditional approaches. Our review emphasizes key outcomes in the field, including evidence of probiotics reducing disease severity and insights into host-microbiome crosstalk that have informed novel therapeutic strategies. These findings underscore the potential of microbiome-based interventions to promote physiological function alongside existing strategies aimed at enhancing host immune responses and pathogen destruction. This narrative review explores microbiome therapeutics as next-generation treatments for infectious diseases, focusing on the application of probiotics and their role in host-microbiome interactions. While offering a novel perspective grounded in a cooperative defense system, this review also addresses the practical challenges and limitations in translating these advancements into clinical settings.

RevDate: 2024-12-17

Morales C, Ballestero L, Del Río P, et al (2024)

Should the Faecal Microbiota Composition Be Determined to Certify a Faecal Donor?.

Diagnostics (Basel, Switzerland), 14(23): pii:diagnostics14232635.

BACKGROUND/OBJECTIVES: Faecal microbiota transplantation (FMT) is considered a safe and effective therapy for recurrent Clostridioides difficile infection. It is the only current clinical indication for this technique, although numerous clinical research studies and trials propose its potential usefulness for treating other pathologies. Donor selection is a very rigorous process, based on a personal lifestyle interview and the absence of known pathogens in faeces and serum, leading to only a few volunteers finally achieving the corresponding certification. However, despite the high amount of data generated from the ongoing research studies relating microbiota and health, there is not yet a consensus defining what is a "healthy" microbiota. To date, knowledge of the composition of the microbiota is not a requirement to be a faecal donor. The aim of this work was to evaluate whether the analysis of the composition of the microbiota by massive sequencing of 16S rDNA could be useful in the selection of the faecal donors.

METHODS: Samples from 10 certified donors from Mikrobiomik Healthcare Company were collected and sequenced using 16S rDNA in a MiSeq (Illumina) platform. Alpha (Chao1 and Shannon indices) and beta diversity (Bray-Curtis) were performed using the bioinformatic web server Microbiome Analyst. The differences in microbial composition at the genera and phyla levels among the donors were evaluated.

RESULTS: The microbial diversity metric by alpha diversity indexes showed that most donors exhibited a similar microbial diversity and richness, whereas beta diversity by 16S rDNA sequencing revealed significant inter-donor differences, with a more stable microbial composition over time in some donors. The phyla Bacillota and Bacteroidota were predominant in all donors, while the density of other phyla, such as Actinomycota and Pseudomonota, varied among individuals. Each donor exhibited a characteristic genera distribution pattern; however, it was possible to define a microbiome core consisting of the genera Agathobacter, Eubacterium, Bacteroides, Clostridia UCG-014 and Akkermansia. Conclusions: The results suggest that donor certification does not need to rely exclusively on their microbiota composition, as it is unique to each donor. While one donor showed greater microbial diversity and richness, clear criteria for microbial normality and health have yet to be established. Therefore, donor certification should focus more on clinical and lifestyle aspects.

RevDate: 2024-12-16

Joos R, Boucher K, Lavelle A, et al (2024)

Author Correction: Examining the healthy human microbiome concept.

RevDate: 2024-12-16
CmpDate: 2024-12-16

Bhatnagar K, Jha K, Dalal N, et al (2024)

Exploring micronutrients and microbiome synergy: pioneering new paths in cancer therapy.

Frontiers in immunology, 15:1442788.

The human microbiome is the complex ecosystem consisting of trillions of microorganisms that play a key role in developing the immune system and nutrient metabolism. Alterations in the gut microbiome have been linked to cancer initiation, progression, metastasis, and response to treatment. Accumulating evidence suggests that levels of vitamins and minerals influence the gut environment and may have implications for cancer risk and progression. Bifidobacterium has been reported to reduce the colorectal cancer risk by binding to free iron. Additionally, zinc ions have been shown to activate the immune cells and enhance the effectiveness of immunotherapy. Higher selenium levels have been associated with a reduced risk of several cancers, including colorectal cancer. In contrast, enhanced copper uptake has been implicated in promoting cancer progression, including colon cancer. The interaction between cancer and gut bacteria, as well as dysbiosis impact has been studied in animal models. The interplay between prebiotics, probiotics, synbiotics, postbiotics and gut bacteria in cancer offers the diverse physiological benefits. We also explored the particular probiotic formulations like VSL#3, Prohep, Lactobacillus rhamnosus GG (LGG), etc., for their ability to modulate immune responses and reduce tumor burden in preclinical models. Targeting the gut microbiome through antibiotics, bacteriophage, microbiome transplantation-based therapies will offer a new perspective in cancer research. Hence, to understand this interplay, we outline the importance of micronutrients with an emphasis on the immunomodulatory function of the microbiome and highlight the microbiome's potential as a target for precision medicine in cancer treatment.

RevDate: 2024-12-15

Skurnik M (2024)

Scholarly discussion on the classification and electron microscopy analysis of lytic phage EC BD.

RevDate: 2024-12-11

Hodgkiss R, A Acharjee (2024)

Unravelling metabolite-microbiome interactions in inflammatory bowel disease through AI and interaction-based modelling.

Biochimica et biophysica acta. Molecular basis of disease pii:S0925-4439(24)00612-4 [Epub ahead of print].

Inflammatory Bowel Diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract and colon affecting approximately 7 million individuals worldwide. The knowledge of specific pathology and aetiological mechanisms leading to IBD is limited, however a reduced immune system, antibiotic use and reserved diet may initiate symptoms. Dysbiosis of the gut microbiome, and consequently a varied composition of the metabolome, has been extensively linked to these risk factors and IBD. Metagenomic sequencing and liquid-chromatography mass spectrometry (LC-MS) of N = 220 fecal samples by Fransoza et al., provided abundance data on microbial genera and metabolites for use in this study. Identification of differentially abundant microbes and metabolites was performed using a Wilcoxon test, followed by feature selection of random forest (RF), gradient-boosting (XGBoost) and least absolute shrinkage operator (LASSO) models. The performance of these features was then validated using RF models on the Human Microbiome Project 2 (HMP2) dataset and a microbial community (MICOM) model was utilised to predict and interpret the interactions between key microbes and metabolites. The Flavronifractor genus and microbes of the families Lachnospiraceae and Oscillospiraceae were found differential by all models. Metabolic pathways commonly influenced by such microbes in IBD were CoA biosynthesis, bile acid metabolism and amino acid production and degradation. This study highlights distinct interactive microbiome and metabolome profiles within IBD and the highly potential pathways causing disease pathology. It therefore paves way for future investigation into new therapeutic targets and non-invasive diagnostic tools for IBD.

RevDate: 2024-12-10

Sinkko H, Olah P, Yang Y, et al (2024)

Taxonomic and functional profiling of skin microbiome in psoriasis.

The British journal of dermatology pii:7919383 [Epub ahead of print].

RevDate: 2024-12-10

Yang W, Wu K, Chen H, et al (2024)

Emerging role of rare earth elements in biomolecular functions.

The ISME journal pii:7918809 [Epub ahead of print].

The importance of rare earth elements is increasingly recognized due to the increased demand for their mining and separation. This demand is driving research on the biology of rare earth elements. Biomolecules associated with rare earth elements include rare earth element-dependent enzymes (methanol dehydrogenase XoxF, ethanol dehydrogenase ExaF/PedH), rare earth element-binding proteins, and the relevant metallophores. Traditional (chemical) separation methods for rare earth elements harvesting and separation are typically inefficient, while causing environmental problems, whereas bioharvesting, potentially, offers more efficient, more green platforms. Here, we review the current state of research on the biological functions of rare earth element-dependent biomolecules, and the characteristics of the relevant proteins, including the specific amino acids involved in rare earth metal binding. We also provide an outlook at strategies for further understanding of biological processes and the potential applications of rare earth element-dependent enzymes and other biomolecules.

RevDate: 2024-12-10

Han H, Choi YH, Kim SY, et al (2024)

Optimizing microbiome reference databases with PacBio full-length 16S rRNA sequencing for enhanced taxonomic classification and biomarker discovery.

Frontiers in microbiology, 15:1485073.

BACKGROUND: The study of the human microbiome is crucial for understanding disease mechanisms, identifying biomarkers, and guiding preventive measures. Advances in sequencing platforms, particularly 16S rRNA sequencing, have revolutionized microbiome research. Despite the benefits, large microbiome reference databases (DBs) pose challenges, including computational demands and potential inaccuracies. This study aimed to determine if full-length 16S rRNA sequencing data produced by PacBio could be used to optimize reference DBs and be applied to Illumina V3-V4 targeted sequencing data for microbial study.

METHODS: Oral and gut microbiome data (PRJNA1049979) were retrieved from NCBI. DADA2 was applied to full-length 16S rRNA PacBio data to obtain amplicon sequencing variants (ASVs). The RDP reference DB was used to assign the ASVs, which were then used as a reference DB to train the classifier. QIIME2 was used for V3-V4 targeted Illumina data analysis. BLAST was used to analyze alignment statistics. Linear discriminant analysis Effect Size (LEfSe) was employed for discriminant analysis.

RESULTS: ASVs produced by PacBio showed coverage of the oral microbiome similar to the Human Oral Microbiome Database. A phylogenetic tree was trimmed at various thresholds to obtain an optimized reference DB. This established method was then applied to gut microbiome data, and the optimized gut microbiome reference DB provided improved taxa classification and biomarker discovery efficiency.

CONCLUSION: Full-length 16S rRNA sequencing data produced by PacBio can be used to construct a microbiome reference DB. Utilizing an optimized reference DB can increase the accuracy of microbiome classification and enhance biomarker discovery.

RevDate: 2024-12-09

Poncet R, O Gargominy (2024)

In the Shadow of Medicine: The Glaring Absence of Occurrence Records of Human-Hosted Biodiversity.

Online journal of public health informatics, 16:e60140 pii:v16i1e60140.

Microbial diversity is vast, with bacteria playing a crucial role in human health. However, occurrence records (location, date, observer, and host interaction of human-associated bacteria) remain scarce. This lack of information hinders our understanding of human-microbe relationships and disease prevention. In this study, we show that existing solutions such as France's Système d'Information sur le Patrimoine Naturel framework, can be used to efficiently collect and manage occurrence data on human-associated bacteria. This user-friendly system allows medical personnel to easily share and access data on bacterial pathogens. By adopting similar national infrastructures and treating human-associated bacteria as biodiversity data, we can significantly improve public health management and research, and our understanding of the One Health concept, which emphasizes the interconnectedness of human, animal, and environmental health.

RevDate: 2024-12-09

Burton JP, Kofoed RH, R Rust (2024)

Science around the world.

Trends in molecular medicine, 30(3):197-199.

RevDate: 2024-12-08

Porcari S, Mullish BH, Asnicar F, et al (2024)

International consensus statement on microbiome testing in clinical practice.

The lancet. Gastroenterology & hepatology pii:S2468-1253(24)00311-X [Epub ahead of print].

There is growing interest in the potential exploitation of the gut microbiome as a diagnostic tool in medicine, but evidence supporting its clinical usefulness is scarce. An increasing number of commercial providers offer direct-to-consumer microbiome diagnostic tests without any consensus on their regulation or any proven value in clinical practice, which could result in considerable waste of individual and health-care resources and potential drawbacks in the clinical management of patients. We convened an international multidisciplinary expert panel to standardise best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value. We also evaluated current knowledge gaps and future directions in this field. We aimed to establish a framework to regulate the provision of microbiome testing and minimise the use of inappropriate tests and pave the way for the evidence-based development and use of human microbiome diagnostics in clinical medicine.

RevDate: 2024-12-05
CmpDate: 2024-12-06

Ma ZS (2024)

Revisiting microgenderome: detecting and cataloguing sexually unique and enriched species in human microbiomes.

BMC biology, 22(1):284.

BACKGROUND: Microgenderome or arguably more accurately microsexome refers to studies on sexual dimorphism of human microbiomes aimed at investigating bidirectional interactions between human microbiomes, sex hormones, and immune systems. It is important because of its implications to disease susceptibility and therapy, in which men and women demonstrate divergence in many diseases especially autoimmune diseases. In a previous report [1], we presented analyses of several key ecological aspects of microgenderome by leveraging the large datasets of the HMP (human microbiome project) but failed to offer species-level composition differences such as sexually unique species (US) and enriched species (ES). Existing approaches, for such tasks, including differential species relative abundance analysis and differential network analysis, possess certain limitations given that virtually all rely on species abundance alone or are univariate, while ignoring species distribution information across samples. Obviously, it is both species abundance and distribution that shape/drive the structure and dynamics of human microbiomes, and both should be equally responsible for the universal heterogeneity of microbiomes including the sexual dimorphism.

RESULTS: Here, we fill the gap by taking advantages of a recently developed computational algorithm, species specificity, and specificity diversity (SSD) framework (refer to the companion article) to reanalyze the HMP and complementary seminovaginal microbiome datasets. The SSD framework can randomly search and catalogue the sexually specific unique/enriched species with statistical rigor, guided by species specificity (a synthetic metric of abundance and distribution) and specificity diversity (SD). The SSD framework reveals that men seem to have more unique species than women in their gut and reproductive system microbiomes, but women seem to have more unique species than men in the airway, oral, and skin microbiomes, which is likely due to sexual dimorphism in the hormone and immune systems. We further investigate co-dependency and heterogeneity of those sexually unique/enriched species across 15 body sites, with core/periphery network analyses.

CONCLUSIONS: This study not only produced sexually unique/enriched species in the human microbiomes and analyzed their codependency and heterogeneity but also further validated the robustness of the SSD framework presented in the companion article, by performing all negative control tests based on the HMP gut microbiome samples.

RevDate: 2024-12-04

Liu D, Siguenza NE, Zarrinpar A, et al (2022)

Methods of DNA introduction for the engineering of commensal microbes.

Engineering microbiology, 2(4):100048.

The microbiome is an essential component of ecological systems and is comprised of a diverse array of microbes. Over the past decades, the accumulated observational evidence reveals a close correlation between the microbiome and human health and disease. Many groups are now manipulating individual microbial strains, species and the community as a whole to gain a mechanistic understanding of the functions of the microbiome. Here, we discuss three major approaches for introducing DNA to engineer model bacteria and isolated undomesticated bacteria, including transformation, transduction, and conjugation. We provide an overview of these approaches and describe the advantages and limitations of each method. In addition, we highlight examples of human microbiome engineering using these approaches. Finally, we provide perspectives for the future of microbiome engineering.

RevDate: 2024-12-03

He Z, Yu J, Gong J, et al (2024)

Campylobacterjejuni-derived cytolethal distending toxin promotes colorectal cancer metastasis.

Cell host & microbe pii:S1931-3128(24)00437-2 [Epub ahead of print].

Various forms of solid tumors harbor intracellular bacteria, but the physiological consequences of these microorganisms are poorly understood. We show that Campylobacter is significantly enriched in primary colorectal cancer (CRC) lesions from patients with metastasis. Campylobacterjejuni-derived cytolethal distending toxin (CDT) promotes CRC metastasis through JAK2-STAT3-MMP9 signaling in liver or pulmonary metastatic mice models, as confirmed in C. jejuni-infected human colonic tissue and CDT-treated colonic tumoroids from patients. Genetic deletion of cdtB (ΔcdtB) or purified CdtB protein demonstrates that the genotoxin is essential for C. jejuni's pro-metastatic property. In C.-jejuni-colonized mice, increased translocation of CDT-producing C. jejuni to extraintestinal implanted tumors potentially leads to accelerated metastasis of these tumors. Overall, these findings demonstrate that an intratumor-bacteria-derived genotoxin accelerates tumor metastasis, potentially opening a new diagnostic and therapeutic avenue for cancer management.

RevDate: 2024-12-03

Zhang Y, Schluter J, Zhang L, et al (2024)

Review and revamp of compositional data transformation: A new framework combining proportion conversion and contrast transformation.

Computational and structural biotechnology journal, 23:4088-4107.

Due to the development of next-generation sequencing technology and an increased appreciation of their role in modulating host immunity and their potential as therapeutic agents, the human microbiome has emerged as a key area of interest in various biological investigations of human health and disease. However, microbiome data present a number of statistical challenges not addressed by existing methods, such as the varying sequencing depth, the compositionality, and zero inflation. Solutions like scaling and transformation methods help to mitigate heterogeneity and release constraints, but often introduce biases and yield inconsistent results on the same data. To address these issues, we conduct a systematic review of compositional data transformation, with a particular focus on the connection and distinction of existing techniques. Additionally, we create a new framework that enables the development of new transformations by combining proportion conversion with contrast transformations. This framework includes well-known methods such as Additive Log Ratio (ALR) and Centered Log Ratio (CLR) as special cases. Using this framework, we develop two novel transformations-Centered Arcsine Contrast (CAC) and Additive Arcsine Contrast (AAC)-which show enhanced performance in scenarios with high zero-inflation. Moreover, our findings suggest that ALR and CLR transformations are more effective when zero values are less prevalent. This comprehensive review and the innovative framework provide microbiome researchers with a significant direction to enhance data transformation procedures and improve analytical outcomes.

RevDate: 2024-12-02
CmpDate: 2024-12-02

Martins FP, Andrade-Silva J, Teixeira BL, et al (2024)

Oral microbiome test as an alternative diagnostic tool for gastric alterations: A prospective, bicentric cross-sectional study.

PloS one, 19(12):e0314660 pii:PONE-D-23-43704.

The human microbiome plays a pivotal role in influencing various physiological processes and maintaining overall well-being, including the gastric system. Current diagnostic tests for gastric diseases often involve invasive procedures, sampling limitations, and medication effects, leading to potential diagnostic errors and discomfort to patients. Considering the connection between oral and gastric microbiomes, this cross-sectional study aimed to assess the diagnostic potential of the oral bacterial profile in patients undergoing upper digestive endoscopy. Oral samples from 266 participants across two Brazilian sites (Belterra and Sao Paulo) were sequenced and subjected to bioinformatic analysis to identify microbiome composition across endoscopy outcome groups, exploring alpha and beta-diversity, richness, and differential abundance and prevalence. Prevotella, Haemophilus, Fusobacterium, Neisseria, and Streptococcus were the most abundant genera observed. No significant associations were found between alpha diversity profiles and endoscopy outcomes; beta diversity analyses similarly showed no correlations. Overall, the study did not establish the oral microbiome as a reliable marker for gastric health, underscoring the necessity for broader studies in the development of non-invasive diagnostic tests.

RevDate: 2024-12-02

Sawan HM, Shroukh W, Abutaima R, et al (2024)

Impact of Jordanian Pharmacists' Knowledge of the Human Microbiome: Has the Practice of Antibiotics and Probiotics Dispensing Been Affected? A Cross-Sectional Study.

Infection and drug resistance, 17:5203-5214.

OBJECTIVE: This study aimed to assess Jordanian pharmacists' knowledge of the human microbiome and the impact of their knowledge on their attitudes and practices toward antibiotics and probiotics.

METHODS: A self-administered survey was designed after reviewing the literature. Participants' demographics were collected, and questions to evaluate pharmacists' knowledge, attitudes, and practices toward antibiotic and probiotic dispensing were asked. The data were analyzed using the Statistical Package for the Social Sciences V.26. Pearson correlations and one-way ANOVA were employed to calculate the significance of knowledge, attitudes, and practices. Statistical significance was considered at p < 0.05.

RESULTS: Of the 333 respondents, around 75% (n=250) had a high level of general knowledge regarding the human gut microbiome. Almost equal proportions of participants had either intermediate or high levels of knowledge about the role of gut bacteria in health (n=164, 49.2%) (n=166, 49.8%), respectively, while almost two-thirds had an intermediate level of knowledge of the role of gut bacteria in disease (n=197, 59.2%). More than half of the participants had a positive attitude toward antibiotics, probiotics, and the human microbiome (n=179, 53.8%), and the majority (n=239, 71.8%) had an intermediate level of practice with them. There was a significant positive correlation between pharmacists' general knowledge of the human microbiome and their positive attitudes (r=0.306, p < 0.01) and practices (r=0.331, p < 0.01) toward antibiotics and probiotics.

CONCLUSION: Study results raise the importance of interventional educational measures to promote healthcare professionals' knowledge of the human microbiome and their potential beneficence on pharmacists' attitudes and practices regarding antibiotics and probiotics dispensing. The results also denote the urgent need for probiotics' clinical guidelines to ensure practice uniformity.

RevDate: 2024-11-29
CmpDate: 2024-11-30

Tang H, Du S, Niu Z, et al (2024)

Nasal, dermal, oral and indoor dust microbe and their interrelationship in children with allergic rhinitis.

BMC microbiology, 24(1):505.

BACKGROUND: Allergic rhinitis (AR) subjects might have their microenvironment changed due to pathogenesis and living environment. Whether the nasal microbe in AR children differs from healthy subjects and how it interplays with dermal, oral and indoor dust microbe needs to be elucidated.

METHODS: In this case-control study, we analyzed and compared the bacterial characterization and associations in nasal, dermal, oral swab samples and dust samples in 62 children with physician-diagnosed AR(cases) and 51 age- and gender-matched healthy ones with no history of allergic diseases(controls). Full-length 16S rRNA sequencing(swabs) and shotgun metagenomics(dust) were applied. Bacterial diversity, composition, abundance difference characteristics and fast expectation-maximization for microbial source tracking(FEAST) analysis were performed and compared between cases and controls.

RESULTS: The α-diversity of dust microorganisms in AR was lower than that in control group (P = 0.034), and the β-diversity indices of microorganisms in nasal cavity (P = 0.020), skin (P = 0.001) and dust (P = 0.004) were significantly different from those in control group. At species levels, a total of 10, 15, 12, and 15 bacterial species were differentially enriched in either cases or controls in nasal, dermal, oral, and dust samples, respectively(Linear Discriminant Analysis(LDA) score > 2, P < 0.05). Staphylococcus epidermidis was the single species simultaneously more abundant in nasal, dermal and dust samples in AR children. By FEAST analysis, 8.85% and 10.11% of S. epidermidis in AR dermal and dust samples came from nasal cavity. These proportions were significantly higher than those in controls (2.70% and 3.86%) (P < 0.05). The same significantly higher transfer proportions(P < 0.05) were observed for Staphylococcus aureus enriched in the nasal cavity in AR children. Classification models by random forest regression at species levels showed, bacterial species enriched in indoor dust, nasal and dermal samples had substantial power in distinguishing AR children from healthy ones, with the highest power in the dust samples (AUC = 0.88) followed by nasal(AUC = 0.81) and dermal ones(AUC = 0.80).

CONCLUSIONS: Our study presented the microbial enrichment characteristics in AR children both in the living environment(dust) and body sites exposed to environment through inhalation(nasal cavity), contact(skin) and ingestion(oral cavity) pathways, respectively. Nasal S.epidermidis and S.aureus had dominant influences on dust and other body sites in AR children.

RevDate: 2024-11-29
CmpDate: 2024-11-30

Marín-Sánchez N, Paredes R, A Borgognone (2024)

Exploring potential associations between the human microbiota and reservoir of latent HIV.

Retrovirology, 21(1):21.

BACKGROUND: The rapid establishment and persistence of latent HIV-1 reservoirs is one of the main obstacles towards an HIV cure. While antiretroviral therapy supresses viral replication, it does not eradicate the latent reservoir of HIV-1-infected cells. Recent evidence suggests that the human microbiome, particularly the gut microbiome, may have the potential to modulate the HIV-1 reservoir. However, literature is limited and the exact mechanisms underlying the role of the microbiome in HIV immunity and potential regulation of the viral reservoir remain poorly understood.

RESULTS: Here, we review updated knowledge on the associations between the human microbiome and HIV reservoir across different anatomical sites, including the gut, the lungs and blood. We provide an overview of the predominant taxa associated with prominent microbiome changes in the context of HIV infection. Based on the current evidence, we summarize the main study findings, with specific focus on consistent bacterial and related byproduct associations. Specifically, we address the contribution of immune activation and inflammatory signatures on HIV-1 persistence. Furthermore, we discuss possible scenarios by which bacterial-associated inflammatory mediators, related metabolites and host immune signatures may modulate the HIV reservoir size. Finally, we speculate on potential implications of microbiome-based therapeutics for future HIV-1 cure strategies, highlighting challenges and limitations inherent in this research field.

CONCLUSIONS: Despite recent advances, this review underscores the need for further research to deepen the understanding of the complex interplay between the human microbiome and HIV reservoir. Further integrative multi-omics assessments and functional studies are crucial to test the outlined hypothesis and to identify potential therapeutic targets ultimately able to achieve an effective cure for HIV.

RevDate: 2024-11-28

Merk LN, Shur AS, Jena S, et al (2024)

Diagnostic and Therapeutic Microbial Circuit with Application to Intestinal Inflammation.

ACS synthetic biology [Epub ahead of print].

Bacteria genetically engineered to execute defined therapeutic and diagnostic functions in physiological settings can be applied to colonize the human microbiome, providing in situ surveillance and conditional disease modulation. However, many engineered microbes can only respond to single-input environmental factors, limiting their tunability, precision, and effectiveness as living diagnostic and therapeutic systems. For engineering microbes to improve complex chronic disorders such as inflammatory bowel disease, the bacteria must respond to combinations of stimuli in the proper context and time. This work implements a previously characterized split activator AND logic gate in the probiotic Escherichia coli strain Nissle 1917 (EcN). Our system can respond to two input signals: the inflammatory biomarker tetrathionate and a second input signal, anhydrotetracycline (aTc), for manual control. We report 4-6 fold induction with a minimal leak when the two chemical signals are present. We model the AND gate dynamics using chemical reaction networks and tune parameters in silico to identify critical perturbations that affect our circuit's selectivity. Finally, we engineer the optimized AND gate to secrete a therapeutic anti-inflammatory cytokine IL-22 using the hemolysin secretion pathway in the probiotic E. coli strain. We used a germ-free transwell model of the human gut epithelium to show that our engineering bacteria produce similar host cytokine responses compared to recombinant cytokine. Our study presents a scalable workflow to engineer cytokine-secreting microbes driven by logical signal processing. It demonstrates the feasibility of IL-22 derived from probiotic EcN with minimal off-target effects in a gut epithelial context.

RevDate: 2024-11-27

Pasolli E, Mauriello IE, Avagliano M, et al (2024)

Bifidobacteriaceae diversity in the human microbiome from a large-scale genome-wide analysis.

Cell reports, 43(12):115027 pii:S2211-1247(24)01378-0 [Epub ahead of print].

We performed a large-scale genome-wide analysis aiming to investigate the prevalence and strain-level diversity of Bifidobacteriaceae species in the human microbiome. We considered 9,528 publicly available human metagenomes and integrated them with 1,192 isolate genomes from different sources. The prevalence and abundance of Bifidobacteriaceae species in humans was linked to multiple host characteristics: they were reduced in older people and enriched in populations characterized by Westernized lifestyles with geography-specific patterns. Phylogenetic analysis highlighted 110 Bifidobacteriaceae species-level genome bins (SGBs), with 32 found in humans and 8 in food and probiotic sources. Functional annotation revealed a great diversity in carbohydrate-active enzyme families across these SGBs. We found potential subspecies for most of the SGBs prevalent in humans and identified patterns driven by age and geography. We provided evidence that strains used in probiotics were rarely identified in humans, with the only exception represented by Bifidobacterium animalis. We finally evaluated that the abundance of Bifidobacteriaceae species exhibited moderate and variable capabilities to predict health status in case-control studies.

RevDate: 2024-11-27

Patjas A, Jokiranta TS, A Kantele (2024)

Urinary tract infections: a retrospective cohort study of (mis)matching antimicrobial therapy and clinical outcome among Finnish adults.

JAC-antimicrobial resistance, 6(6):dlae188.

OBJECTIVES: With the global spread of antimicrobial resistance, treating urinary tract infections (UTIs) is becoming more challenging. Clinical data on UTI outcomes are scarce in cases with antimicrobial treatment mismatching the uropathogens' in vitro susceptibility profiles. We explored the association of (mis)matching antimicrobial treatment and clinical outcomes among patients with either ESBL-producing Enterobacterales (ESBL-PE) or non-ESBL-PE identified in urine samples.

PATIENTS AND METHODS: In 2015-2019, we recruited 18-65-year-old patients with laboratory-confirmed, community-acquired ESBL-PE (n = 130) or non-ESBL-PE (n = 187) UTI. Our study involved collecting data on in vitro susceptibility profiles, antimicrobial therapy (microbiological match/mismatch) and clinical outcomes, and a follow-up of relapses/reinfections.

RESULTS: Non-beta-lactam co-resistance was found more frequent among ESBL-PE than non-ESBL-PE isolates. The initial antimicrobial matched the in vitro susceptibility for 91.6% (164/179) of those with non-ESBL-PE and 46.9% (38/81) with ESBL-PE UTI (P < 0.001). The clinical cure rates in the non-ESBL-PE and ESBL-PE UTI groups were 82.6% (142/172) and 62.2% (74/119) (P < 0.001) for all, 87.3% (131/150) and 83.3% (30/36) for those treated with matching antimicrobials, and 33.3% (5/15) and 41.9% (18/43) for those given mismatching antimicrobials, respectively. Mismatching antimicrobial therapy was not associated with relapse/reinfection over the 3-month follow-up (P = 0.943).

CONCLUSIONS: In our data, (mis)matching microbiological susceptibility is only partially associated with the clinical outcome of UTI: microbiological matching appears to predict clinical cure better than mismatching predicts clinical failure.

RevDate: 2024-11-27

Castro-Vidal ZA, Mathew F, Ibrahim AA, et al (2024)

The Role of Gastrointestinal Dysbiosis and Fecal Transplantation in Various Neurocognitive Disorders.

Cureus, 16(10):e72451.

This review explores the critical role of the human microbiome in neurological and neurodegenerative disorders, focusing on gut-brain axis dysfunction caused by dysbiosis, an imbalance in gut bacteria. Dysbiosis has been linked to diseases such as Alzheimer's disease, Parkinson's disease (PD), multiple sclerosis (MS), and stroke. The gut microbiome influences the central nervous system (CNS) through signaling molecules, including short-chain fatty acids, neurotransmitters, and metabolites, impacting brain health and disease progression. Emerging therapies, such as fecal microbiota transplantation (FMT), have shown promise in restoring microbial balance and alleviating neurological symptoms, especially in Alzheimer's and PD. Additionally, nutritional interventions such as probiotics, prebiotics, and specialized diets are being investigated for their ability to modify gut microbiota and improve patient outcomes. This review highlights the therapeutic potential of gut microbiota modulation but emphasizes the need for further clinical trials to establish the safety and efficacy of these interventions in neurological and mental health disorders.

RevDate: 2024-11-27
CmpDate: 2024-11-27

Wang Z, Kaplan RC, Burk RD, et al (2024)

The Oral Microbiota, Microbial Metabolites, and Immuno-Inflammatory Mechanisms in Cardiovascular Disease.

International journal of molecular sciences, 25(22): pii:ijms252212337.

Cardiovascular diseases (CVDs) remain a leading cause of global morbidity and mortality. Recent advancements in high-throughput omics techniques have enhanced our understanding of the human microbiome's role in the development of CVDs. Although the relationship between the gut microbiome and CVDs has attracted considerable research attention and has been rapidly evolving in recent years, the role of the oral microbiome remains less understood, with most prior studies focusing on periodontitis-related pathogens. In this review, we summarized previously reported associations between the oral microbiome and CVD, highlighting known CVD-associated taxa such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans. We also discussed the interactions between the oral and gut microbes. The potential mechanisms by which the oral microbiota can influence CVD development include oral and systemic inflammation, immune responses, cytokine release, translocation of oral bacteria into the bloodstream, and the impact of microbial-related products such as microbial metabolites (e.g., short-chain fatty acids [SCFAs], trimethylamine oxide [TMAO], hydrogen sulfide [H2S], nitric oxide [NO]) and specific toxins (e.g., lipopolysaccharide [LPS], leukotoxin [LtxA]). The processes driven by these mechanisms may contribute to atherosclerosis, endothelial dysfunction, and other cardiovascular pathologies. Integrated multi-omics methodologies, along with large-scale longitudinal population studies and intervention studies, will facilitate a deeper understanding of the metabolic and functional roles of the oral microbiome in cardiovascular health. This fundamental knowledge will support the development of targeted interventions and effective therapies to prevent or reduce the progression from cardiovascular risk to clinical CVD events.

RevDate: 2024-11-27

Belnap N, Ramsey K, Carvalho ST, et al (2024)

Exploring the Frontier: The Human Microbiome's Role in Rare Childhood Neurological Diseases and Epilepsy.

Brain sciences, 14(11): pii:brainsci14111051.

Emerging research into the human microbiome, an intricate ecosystem of microorganisms residing in and on our bodies, reveals that it plays a pivotal role in maintaining our health, highlighting the potential for microbiome-based interventions to prevent, diagnose, treat, and manage a myriad of diseases. The objective of this review is to highlight the importance of microbiome studies in enhancing our understanding of rare genetic epilepsy and related neurological disorders. Studies suggest that the gut microbiome, acting through the gut-brain axis, impacts the development and severity of epileptic conditions in children. Disruptions in microbial composition can affect neurotransmitter systems, inflammatory responses, and immune regulation, which are all critical factors in the pathogenesis of epilepsy. This growing body of evidence points to the potential of microbiome-targeted therapies, such as probiotics or dietary modifications, as innovative approaches to managing epilepsy. By harnessing the power of the microbiome, we stand to develop more effective and personalized treatment strategies for children affected by this disease and other rare neurological diseases.

RevDate: 2024-11-27
CmpDate: 2024-11-27

Reshetova M, Markin P, Appolonova S, et al (2024)

Tryptophan Metabolites in the Progression of Liver Diseases.

Biomolecules, 14(11): pii:biom14111449.

The aim of this study was to investigate the levels of various tryptophan metabolites in patients with alcoholic liver disease (ALD) and metabolic-associated fatty liver disease (MAFLD) at different stages of the disease. The present study included 44 patients diagnosed with MAFLD, 40 patients diagnosed with ALD, and 14 healthy individuals in the control group. The levels of tryptophan and its 16 metabolites (3-OH anthranilic acid, 5-hydroxytryptophan, 5-methoxytryptamine, 6-hydroxymelatonin, indole-3-acetic acid, indole-3-butyric, indole-3-carboxaldehyde, indole-3-lactic acid, indole-3-propionic acid, kynurenic acid, kynurenine, melatonin, quinolinic acid, serotonin, tryptamine, and xanthurenic acid) in the serum were determined via high-performance liquid chromatography and tandem mass spectrometry. In patients with cirrhosis resulting from MAFLD and ALD, there are significant divergent changes in the serotonin and kynurenine pathways of tryptophan catabolism as the disease progresses. All patients with cirrhosis showed a decrease in serotonin levels ([MAFLD]p = 0.038; [ALD]p < 0.001) and an increase in kynurenine levels ([MAFLD]p = 0.032; [ALD]p = 0.010). A negative correlation has been established between serotonin levels and the FIB-4 index (p < 0.001). The decrease in serotonin pathway metabolites was associated with manifestations of portal hypertension (p = 0.026), the development of hepatocellular insufficiency (p = 0.008) (hypoalbuminemia; hypocoagulation), and jaundice (p < 0.001), while changes in the kynurenine pathway metabolite xanthurenic acid were associated with the development of hepatic encephalopathy (p = 0.044). Depending on the etiological factors of cirrhosis, disturbances in the metabolic profile may be involved in various pathogenetic pathways.

RevDate: 2024-11-26

Agnew A, Humm E, Zhou K, et al (2024)

Structure and identification of the native PLP synthase complex from Methanosarcina acetivorans lysate.

mBio [Epub ahead of print].

Many protein-protein interactions behave differently in biochemically purified forms as compared to their in vivo states. As such, determining native protein structures may elucidate structural states previously unknown for even well-characterized proteins. Here, we apply the bottom-up structural proteomics method, cryoID, toward a model methanogenic archaeon. While they are keystone organisms in the global carbon cycle and active members of the human microbiome, there is a general lack of characterization of methanogen enzyme structure and function. Through the cryoID approach, we successfully reconstructed and identified the native Methanosarcina acetivorans pyridoxal 5'-phosphate (PLP) synthase (PdxS) complex directly from cryogenic electron microscopy (cryo-EM) images of fractionated cellular lysate. We found that the native PdxS complex exists as a homo-dodecamer of PdxS subunits, and the previously proposed supracomplex containing both the synthase (PdxS) and glutaminase (PdxT) was not observed in cellular lysate. Our structure shows that the native PdxS monomer fashions a single 8α/8β TIM-barrel domain, surrounded by seven additional helices to mediate solvent and interface contacts. A density is present at the active site in the cryo-EM map and is interpreted as ribose 5-phosphate. In addition to being the first reconstruction of the PdxS enzyme from a heterogeneous cellular sample, our results reveal a departure from previously published archaeal PdxS crystal structures, lacking the 37-amino-acid insertion present in these prior cases. This study demonstrates the potential of applying the cryoID workflow to capture native structural states at atomic resolution for archaeal systems, for which traditional biochemical sample preparation is nontrivial.IMPORTANCEArchaea are one of the three domains of life, classified as a phylogenetically distinct lineage. There is a paucity of known enzyme structures from organisms of this domain, and this is often exacerbated by characteristically difficult growth conditions and a lack of readily available molecular biology toolkits to study proteins in archaeal cells. As a result, there is a gap in knowledge concerning the mechanisms governing archaeal protein behavior and their impacts on both the environment and human health; case in point, the synthesis of the widely utilized cofactor pyridoxal 5'-phosphate (PLP; a vitamer of vitamin B6, which humans cannot produce). By leveraging the power of single-particle cryo-EM and map-to-primary sequence identification, we determine the native structure of PLP synthase from cellular lysate. Our workflow allows the (i) rapid examination of new or less characterized systems with minimal sample requirements and (ii) discovery of structural states inaccessible by recombinant expression.

RevDate: 2024-11-25

Kajova M, Khawaja T, Levonen I, et al (2024)

Convalescent plasma therapy for COVID-19 - Donor selection strategies and establishment of a plasma bank.

New microbes and new infections, 62:101525.

BACKGROUND: Early in the COVID-19 pandemic, convalescent plasma (CP) emerged as a potentially effective treatment neutralising SARS-CoV-2. Early CP therapy with high neutralising antibody (NAb) titre may benefit COVID-19 outpatients and, in sufficient quantities even some hospitalised patients. This study details the process of setting up a CP bank, containing high- and low-titre CP for a clinical trial.

STUDY DESIGN AND METHODS: We identified 18-65-year-old convalescents with SARS-CoV-2 NAb titres of ≥1:40 in microneutralisation test (MNT). Following eligibility pre-screening, the Finnish Red Cross Blood Service (FRCBS) determined suitability as CP donors.

RESULTS: Of the 6466 COVID-19 convalescents contacted, 1481 provided serum, with 851 (57.5 %) exhibiting NAb titres ≥1:40. Participation barriers included reluctance, advanced age and, for women, insufficient body size. Of the volunteers, 125 were evaluated at FRCBS, with major exclusions for HLA antibodies (42 women), interferon antibodies (five men), and NAb titres waning below 1:20 (16 participants). Finally, 70 underwent plasmapheresis, resulting in 50 suitable CP donors (0.8 % of initial contacts and 3.4 % of those tested for NAb).

DISCUSSION: The process of setting up a CP bank proved challenging. Excessive laboratory workloads during a pandemic hamper their ability to conduct MNT, underscoring the need for rapid screening tests. Only a small proportion of our convalescents exhibited high-titre CP, this fraction declining over time because of waning immunity. Strict plasmapheresis criteria further constrained donor eligibility. Establishing a plasma bank requires meticulous planning to maximize efficiency. Detailed insights from current experiences may prove critical in future pandemics before other remedies and vaccines become available.

RevDate: 2024-11-25

Wang Z, Wu X, Wang Y, et al (2024)

Colonic transendoscopic enteral tubing is revolutionizing intestinal therapeutics, diagnosis, and microbiome research.

Therapeutic advances in gastroenterology, 17:17562848241301574.

The intestine, as a crucial organ of the human body, has remained enigmatic despite the remarkable advancements in modern medical technology. Over the past decades, the invention of endoscopic technology has made the noninvasive intervention of the intestine a reality, expanding diagnostic and therapeutic options for diseases. However, due to the single-treatment feature of endoscopic procedures, continuous or repeated medication administration, sampling, and decompression drainage within the intestine have yet to be fulfilled. These limitations persisted until the invention of colonic transendoscopic enteral tubing (TET) in 2014, which realized repeated fecal microbiota transplantation, medication administration, and decompression drainage for the treatment of colon perforation and intestinal obstruction, as well as in situ dynamic sampling. These breakthroughs have not gone unnoticed, gaining global attention and recommendations from guidelines and consensuses. TET has emerged as a novel microbial research tool that offers new paradigms for human microbiome research. This review aims to update the research progress based on TET.

RevDate: 2024-11-24

Isali I, Almassi N, Nizam A, et al (2024)

State of the Art: The Microbiome in Bladder Cancer.

Urologic oncology pii:S1078-1439(24)00724-5 [Epub ahead of print].

This review assesses the current understanding of the relationship between the human microbiome and BCa. Recognizing how the microbiome affects the tumor microenvironment provides valuable insights into cancer biology, potentially uncovering interactions that could be leveraged to develop innovative therapeutic approaches. By clarifying these intricate microbial-tumor dynamics, novel targets for microbiome-based interventions can be identified, ultimately improving treatment effectiveness and patient outcomes. Current literature lacks comprehensive insights into the effects of BCa treatment on the microbiome and the prevalence of immunotherapy-related toxicities. Further research into the microbiome's role in BCa development could bridge the gap between fundamental research and therapeutic applications. Implementing microbiome surveillance, metagenomic sequencing, and metabolomics in clinical trials could deepen our understanding of BCa and its treatment. This review explores the existing understanding of the urine, tissue, and gut microbiomes and their connections to BCa. Enhanced knowledge of these relationships can pave the way for future research to identify reliable disease predictors, prognostic markers, and novel therapeutic targets.

RevDate: 2024-11-22
CmpDate: 2024-11-22

Zhu Y, Liang X, Zhi M, et al (2024)

Succession of the multi-site microbiome along pancreatic ductal adenocarcinoma tumorigenesis.

Frontiers in immunology, 15:1487242.

BACKGROUND: To investigate microbial characteristics across multibody sites from chronic pancreatitis (CP), through pancreatic benign tumors, to pancreatic ductal adenocarcinoma (PDAC) at different stages.

METHODS: 16S ribosomal RNA (rRNA) amplicon sequencing was conducted on saliva, duodenal fluid, and pancreatic tissue obtained via endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of patients with CP, pancreatic benign tumors, PDAC in stage I/II, III, and IV. The neutral community model (NCM) assessed the microbial assembly contribution and MaAslin2 identified the differential microbes.

RESULTS: From CP to stage IV PDAC patients, there was a marked surge in influence of salivary and duodenal microbiota on constitution of pancreatic microbial communities. Our observations revealed a successive alteration in microbial species across various bodily sites during PDAC tumorigenesis. Notably, Porphyromonas gingivalis, Treponema denticola, Peptoanaerobacter stomatis, Propionibacterium acidifaciens, Porphyromonas endodontalis, Filifactor alocis, etc., sequentially increased along PDAC progression in pancreatic tissue, whereas bacteria commonly used as probiotics Bifidobacterium breve, Lactiplantibacillus plantarum, etc., declined. Furthermore, the sequentially escalating trends of Peptoanaerobacter stomatis and Propionibacterium acidifaciens during PDAC tumorigenesis were mirrored in duodenal fluid and saliva. Porphyromonas gingivalis, Porphyromonas endodontalis, and Filifactor alocis, which intensified from CP to stage IV PDAC in pancreatic tissue, were also found to be enriched in saliva of patients with short-term survival (STS) compared with those with long-term survival (LTS).

CONCLUSIONS: Salivary and duodenal microorganisms were prominent factors in shaping pancreatic microbial landscape in PDAC context. Further exploration of these microbial entities is imperative to unravel their specific roles in PDAC pathogenesis, potentially yielding insights for future therapeutic strategies.

RevDate: 2024-11-22

Teng Z, Li Q, XF Shen (2024)

Correlations of Nasal Microbiome with Allergic Rhinitis and Its Symptoms Severity in Children Progression.

Journal of asthma and allergy, 17:1187-1196.

OBJECTIVE: Human microbiome is involved in the pathogenesis of allergic diseases, but the impact of nasal microbiota on allergic rhinitis (AR) symptoms severity has not been evaluated. This study aimed to characterize nasal microbiome in AR children and its correlations with AR symptoms.

METHODS: According to diagnostic guidelines for AR, 45 AR children and 40 healthy subjects were recruited from July to August in 2023. Based on the total score of nasal symptoms (TNSS), the 45 AR patients were divided into a mild AR group (MAR) (n = 16) and a moderate or severe AR group (MSAR) (n = 29). Nasal swabs were collected for microbiome analysis using 16S-rDNA sequencing.

RESULTS: The Simpson and Shannon indices were significantly higher in the AR group compared to the health control group, indicating an increase of nasal microbiota at the species evenness level in AR children. Moreover, the species evenness was significantly increased in the MSAR group compared to the MAR group. Staphylococcus (member of the Firmicutes phylum) was significantly dominant in the AR group, but Moraxella (member of the Proteobacteria phylum) was significantly dominant in the CG group. The LEfSe analysis showed that the mean relative abundances of Ralstonia in the MSAR group was higher than that in the MAR group. Meanwhile, the abundance divided by Ralstonia of Spearman correlation coefficients was positively correlated with the TNSS of AR symptoms (r = 0.4, P = 0.009).

CONCLUSION: The elevation of species evenness in nasal microbiome was likely related to the aggravation of AR symptoms. The Ralstonia may play a pro-inflammatory role in AR.

RevDate: 2024-11-22

Nguyen UT, Salamzade R, Sandstrom S, et al (2024)

Large-scale investigation for antimicrobial activity reveals novel defensive species across the healthy skin microbiome.

bioRxiv : the preprint server for biology pii:2024.11.04.621544.

The human skin microbiome constitutes a dynamic barrier that can impede pathogen invasion by producing antimicrobial natural products. Gene clusters encoding for production of secondary metabolites, biosynthetic gene clusters (BGCs), that are enriched in the human skin microbiome relative to other ecological settings, position this niche as a promising source for new natural product mining. Here, we introduce a new human microbiome isolate collection, the EPithelial Isolate Collection (EPIC). It includes a large phylogenetically diverse set of human skin-derived bacterial strains from eight body sites. This skin collection, consisting of 980 strains is larger and more diverse than existing resources, includes hundreds of rare and low-abundance species, and hundreds of unique BGCs. Using a large-scale co-culture screen to assess 8,756 pairwise interactions between skin-associated bacteria and potential pathogens, we reveal broad antifungal activity by skin microbiome members. Integrating 287 whole isolate genomes and 268 metagenomes from sampling sites demonstrates that while the distribution of BGC types is stable across body sites, specific gene cluster families (GCFs), each predicted to encode for a distinct secondary metabolite, can substantially vary. Sites that are dry or rarely moist harbor the greatest potential for discovery of novel bioactive metabolites. Among our discoveries are four novel bacterial species, three of which exert significant and broad-spectrum antifungal activity. This comprehensive isolate collection advances our understanding of the skin microbiomes biosynthetic capabilities and pathogen-fighting mechanisms, opening new avenues towards antimicrobial drug discovery and microbiome engineering.

RevDate: 2024-11-21

Yu J, Feng L, Luo Z, et al (2024)

Interleukin-10 deficiency suppresses colorectal cancer metastasis by enriching gut Parabacteroides distasonis.

Journal of advanced research pii:S2090-1232(24)00543-5 [Epub ahead of print].

INTRODUCTION: The intricate interplay of interleukin-10 (IL-10) and gut microbiota influences tumor development and progression, yet the impacts on colorectal cancer (CRC) metastasis remain incompletely understood.

METHODS: The impact of Il10 deficiency on CRC metastasis was first evaluated in CRC metastasis tumor samples and mouse model. Antibiotic sterilization and fecal microbiota transplantation (FMT) experiment were used to assess the role of gut microbiota in IL-10 mediated CRC metastasis, and full-length 16S rDNA sequencing analysis further identified the potential target bacteria influencing CRC metastasis. The inhibitory effect of Parabacteroides distasonis (P. distasonis) on CRC metastasis was evaluated by oral administration in mice. Key metabolites involved in P. distasonis inhibition of CRC metastasis was identified by widely-targeted metabolome analysis and validated both in vivo and in vitro. The underlying mechanisms of P-hydroxyphenyl acetic acid (4-HPAA) inhibiting CRC metastasis was investigated via RNA-sequencing and validated in cellular experiments.

RESULTS: We revealed that serum IL-10 levels were markedly elevated in metastatic CRC patients compared to non-metastatic cases. In parallel, Il10-deficiency (Il10[-/]) in mice resulted in decreased CRC metastasis in a gut microbiota-dependent manner. Mechanistically, Il10[-/-] mice reshaped gut microbiota composition, notably enriching P. distasonis. The enriched P. distasonis produced 4-HPAA, which activated the aryl hydrocarbon receptor (AHR) and subsequently inhibited the expression of VEGFA, a typical oncogene, thereby sequentially suppressing CRC metastasis. Importantly, engineered bacteria capable of producing 4-HPAA effectively hindered CRC metastasis. Furthermore, AHR depletion significantly disrupted the 4-HPAA-induced reduction in CRC cell migration and the inhibition of metastasis in both in vitro and in vivo lung metastasis mouse models.

CONCLUSIONS: These findings demonstrate the significance of IL-10 deficiency in suppressing CRC metastasis through the 4-HPPA-AHR-VEGFA axis mediated by gut P. distasonis, suggesting that P. distasonis or 4-HPAA supplementation could offer a promising therapeutic strategy for CRC metastasis prevention.

RevDate: 2024-11-21

Talukdar D, Sarkar M, Ahrodia T, et al (2024)

Previse preterm birth in early pregnancy through vaginal microbiome signatures using metagenomics and dipstick assays.

iScience, 27(11):111238.

Annually, in India, 13% of all newborns are preterm, accounting for 23.4% of preterm birth (PTB) globally. The composition and diversity of the vaginal microbiome have a notable degree of ethnic inequality. For understanding differences in vaginal microbiome composition and functions between adverse and normal pregnancy, we have collected, processed and sequenced 600 high vaginal swab (HVS) samples across the three trimesters of pregnancy from 140 women who delivered at term and 60 women who delivered PTB, adopting a targeted metagenomics approach. The microbial signatures in HVS samples showed Lactobacillus genera to be highly abundant in term birth (TB), while in early pregnancy the abundances of Gardnerella, Atopobium, and Sneathia were found to be high in PTB. We further extended our analysis, identified specific microbial genomic signatures, and developed a dipstick assay for rapid identification of PTB-associated microbiota in HVS samples in low-resource settings.

RevDate: 2024-11-20

Pino A, Hiippala K, Ronkainen A, et al (2024)

Adhesion Properties and Pathogen Inhibition of Vaginal-Derived Lactobacilli.

Probiotics and antimicrobial proteins [Epub ahead of print].

In the present study, twenty-seven (27) lactobacilli strains, isolated from the vagina of healthy Italian women of reproductive age, were screened for probiotic properties. The strains were evaluated for antagonistic activity against pathogens, adhesion abilities, and potential to displace and/or inhibit the adhesion of previously adhered pathogens as a primary strain selection criterion. Overall, all the tested lactobacilli inhibited at least three pathogens, and the majority of them exhibited antimicrobial activity against Enterobacter cloacae DSM 30054, Pseudomonas aeruginosa DSM 3227, and Pseudomonas aeruginosa DSM 1117. The complete neutralization of antimicrobial activity after cell-free supernatant (CFS) neutralization suggested a pivotal role for lactic acid or other organic acids secreted by the lactobacilli. The strains showed variability in their adhesion levels, but all tested strains adhered to both human colonic epithelial cells (HT-29) and vaginal cells (VK2/E6E7) with adhesion percentages exceeding 1%. The ability to displace or inhibit pathogens was dependent on the pathogen and the lactobacilli strain; the pathogen displacement levels ranged from 9 to 82%, while pathogen exclusion levels varied from 1 to 99%. In conclusion, this study demonstrates the protective effect of vaginal lactobacilli against pathogens and confirms the suitability of the vaginal microbiota as a source of potential probiotic strains. The selected lactobacilli hold promise for the formulation of supplements to enhance genitourinary tract health.

RevDate: 2024-11-20
CmpDate: 2024-11-20

Dong PT, Shi W, He X, et al (2024)

Adhesive interactions within microbial consortia can be differentiated at the single-cell level through expansion microscopy.

Proceedings of the National Academy of Sciences of the United States of America, 121(48):e2411617121.

Investigating microbe-microbe interactions at the single-cell level is critical to unraveling the ecology and dynamics of microbial communities. In many situations, microbes assemble themselves into densely packed multispecies biofilms. The density and complexity pose acute difficulties for visualizing individual cells and analyzing their interactions. Here, we address this problem through an unconventional application of expansion microscopy, which allows for the "decrowding" of individual bacterial cells within a multispecies community. Expansion microscopy generally has been carried out under isotropic expansion conditions and used as a resolution-enhancing method. In our variation of expansion microscopy, we carry out expansion under heterotropic conditions; that is, we expand the space between bacterial cells but not the space within individual cells. The separation of individual bacterial cells from each other reflects the competition between the expansion force pulling them apart and the adhesion force holding them together. We employed heterotropic expansion microscopy to study the relative strength of adhesion in model biofilm communities. These included mono- and dual-species Streptococcus biofilms and a three-species synthetic community (Fusobacterium nucleatum, Streptococcus mutans, and Streptococcus sanguinis) under conditions that facilitated interspecies coaggregation. Using adhesion mutants, we investigated the interplay between F. nucleatum outer membrane protein RadD and different Streptococcus species. We also examined the Schaalia-TM7 epibiont association. Quantitative proximity analysis was used to evaluate the separation of individual microbial members. Our study demonstrates that heterotropic expansion microscopy can "decrowd" dense biofilm communities, improve visualization of individual bacterial members, and enable analysis of microbe-microbe adhesive interactions at the single-cell level.

RevDate: 2024-11-20

Liu R, Wang Y, D Cheng (2024)

Micro-DeMix: a mixture beta-multinomial model for investigating the heterogeneity of the stool microbiome compositions.

Bioinformatics (Oxford, England) pii:7905136 [Epub ahead of print].

MOTIVATION: Extensive research has uncovered the critical role of the human gut microbiome in various aspects of health, including metabolism, nutrition, physiology, and immune function. Fecal microbiota is often used as a proxy for understanding the gut microbiome, but it represents an aggregate view, overlooking spatial variations across different gastrointestinal (GI) locations. Emerging studies with spatial microbiome data collected from specific GI regions offer a unique opportunity to better understand the spatial composition of the stool microbiome.

RESULTS: We introduce Micro-DeMix, a mixture beta-multinomial model that deconvolutes the fecal microbiome at the compositional level by integrating stool samples with spatial microbiome data. Micro-DeMix facilitates the comparison of microbial compositions across different GI regions within the stool microbiome through a hypothesis-testing framework. We demonstrate the effectiveness and efficiency of Micro-DeMix using multiple simulated data sets and the Inflammatory Bowel Disease (IBD) data from the NIH Integrative Human Microbiome Project.

The R package is available at https://github.com/liuruoqian/MicroDemix.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

RevDate: 2024-11-19

Li N, Li Y, Huang Z, et al (2024)

Faecal phageome transplantation alleviates intermittent intestinal inflammation in IBD and the timing of transplantation matters: a preclinical proof-of-concept study in mice.

RevDate: 2024-11-19

Yang J, Sun S, Sun N, et al (2024)

HMMER-extractor: An auxiliary toolkit for identifying genomic macromolecular metabolites based on hidden Markov models.

International journal of biological macromolecules pii:S0141-8130(24)08476-9 [Epub ahead of print].

Human microbiome contains various microbial macromolecules with important biological functions. The Hidden Markov Models (HMMs) can overcome the problem of low similarity sequences with distant relationships and are widely implemented within various sequence alignment softwares. However, the HMM-based sequence alignments can generate a large number of results, how to quickly screen and batch extract target homologs from microbiomes is the major sticking points. It is necessary to develop an integrated gene filter and extraction pipeline to quickly and accurately screen homologs. Here, we introduced the HMMER-Extractor for amino acids or nucleotide sequences extraction, which was a supporting toolkit through provided filtering scores and an iterative keyword matching (IKM) logic. To make it more user-friendly and accessible, we further presented a visualized web server platform. An interactive HTML output provided a user-friendly way to browse homologous annotations and sequence extraction. The web server provided the community with a streamlined and user-friendly interface to analyze microbiomes. Through the HMMER-Extractor, we constructed a cardiovascular disease related gene dataset of the macromolecular metabolite trimethylamine (TMA) and lipopolysaccharide (LPS) based on 46,699 bacterial genomes from human gut. Approximately 21,014 and 1961 bacterial strains were identified to contain the cnt or cut operon of TMA, and the waa gene cluster of LPS, respectively. The Escherichia coli occupied the largest proportion among all the bacterial species, which belonged to the phyla Firmicutes. The HMMER-Extractor toolkit is an integrated pipeline and has been proven to be accurate and fast in extracting target macromolecular encoding genes from microbial genomes.

RevDate: 2024-11-18

Shete O, TS Ghosh (2024)

Normal Gut Microbiomes in Diverse Populations: Clinical Implications.

Annual review of medicine [Epub ahead of print].

The human microbiome is a sensor and modulator of physiology and homeostasis. Remarkable tractability underpins the promise of therapeutic manipulation of the microbiome. However, the definition of a normal or healthy microbiome has been elusive. This is in part due to the underrepresentation of minority groups and major global regions in microbiome studies to date. We review studies of the microbiome in different populations and highlight a commonality among health-associated microbiome signatures along with major drivers of variation. We also provide an overview of microbiome-associated therapeutic interventions for some widespread, widely studied diseases. We discuss sources of bias and the challenges associated with defining population-specific microbiome reference bases. We propose a roadmap for defining normal microbiome references that can be used for population-customized microbiome therapeutics and diagnostics.

RevDate: 2024-11-18

Chen XY, Liu Y, Zhu WB, et al (2024)

Arming oncolytic M1 virus with gasdermin E enhances antitumor efficacy in breast cancer.

iScience, 27(11):111148.

Pyroptosis, driven by the N-terminal domain of gasdermin proteins (GSDM), promotes antitumor immunity by attracting lymphocytes to the tumor microenvironment (TME). However, current pyroptosis-inducing therapies like drug injections and phototherapy are limited to localized treatments, making them unsuitable for widespread or microscopic metastatic lesions. This study engineered oncolytic M1 viruses (rM1-mGSDME_FL and rM1-mGSDME_NT) to selectively deliver GSDME to tumor cells. These modified viruses enhanced tumor cell death in breast cancer models, suppressed tumor growth, extended survival in mice, and boosted immune cell infiltration, demonstrating significant anticancer potential through pyroptosis induction.

RevDate: 2024-11-15

Zelasko S, Swaney MH, Sandstrom S, et al (2024)

Early-life Upper Airway Microbiota are Associated with Decreased Lower Respiratory Tract Infections.

The Journal of allergy and clinical immunology pii:S0091-6749(24)01189-8 [Epub ahead of print].

Microbial interactions mediating colonization resistance play key roles within the human microbiome, shaping susceptibility to infection from birth. To gain insight into microbiome-mediated defenses and respiratory pathogen colonization dynamics, we sequenced and analyzed nasal (n=229) and oral (n=210) microbiomes with associated health/environmental data from our Wisconsin Infant Study Cohort at age 24-months. Participants with early-life lower respiratory tract infection (LRTI) were more likely to be formula-fed, attend daycare, and experience wheezing. Shotgun metagenomic sequencing with detection of viral and bacterial respiratory pathogens revealed nasal microbiome composition to associate with prior LRTI - namely lower alpha diversity, depletion of Prevotella, and enrichment of Moraxella catarrhalis including drug-resistant strains. Prevotella originating from healthy microbiomes had higher biosynthetic gene cluster abundance and exhibited contact-independent inhibition of M. catarrhalis, suggesting interbacterial competition impacts nasal pathogen colonization. This work advances understanding of protective host-microbial interactions occurring in airway microbiomes that alter infection susceptibility in early-life.

RevDate: 2024-11-15

Pawlik MT, Rinneberg G, Koch A, et al (2024)

Is there a rationale for hyperbaric oxygen therapy in the patients with Post COVID syndrome? : A critical review.

European archives of psychiatry and clinical neuroscience [Epub ahead of print].

The SARS-CoV-2 pandemic has resulted in 762 million infections worldwide from 2020 to date, of which approximately ten percent are suffering from the effects after infection in 2019 (COVID-19) [1, 40]. In Germany, it is now assumed that at least one million people suffer from post-COVID condition with long-term consequences. These have been previously reported in diseases like Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS). Symptoms show a changing variability and recent surveys in the COVID context indicate that 10-30 % of outpatients, 50 to 70% of hospitalised patients suffer from sequelae. Recent data suggest that only 13% of all ill people were completely free of symptoms after recovery [3, 9]. Current hypotheses consider chronic inflammation, mitochondrial dysfunction, latent viral persistence, autoimmunity, changes of the human microbiome or multilocular sequelae in various organ system after infection. Hyperbaric oxygen therapy (HBOT) is applied since 1957 for heart surgery, scuba dive accidents, CO intoxication, air embolisms and infections with anaerobic pathogens. Under hyperbaric pressure, oxygen is physically dissolved in the blood in higher concentrations and reaches levels four times higher than under normobaric oxygen application. Moreover, the alternation of hyperoxia and normoxia induces a variety of processes at the cellular level, which improves oxygen supply in areas of locoregional hypoxia. Numerous target gene effects on new vessel formation, anti-inflammatory and anti-oedematous effects have been demonstrated [74]. The provision of intermittently high, local oxygen concentrations increases repair and regeneration processes and normalises the predominance of hyperinflammation. At present time only one prospective, randomized and placebo-controlled study exists with positive effects on global cognitive function, attention and executive function, psychiatric symptoms and pain interference. In conclusion, up to this date HBO is the only scientifically proven treatment in a prospective randomized controlled trial to be effective for cognitive improvement, regeneration of brain network and improvement of cardiac function. HBOT may have not only theoretical but also potential impact on targets of current pathophysiology of Post COVID condition, which warrants further scientific studies in patients.

RevDate: 2024-11-15

Shah AB, SH Shim (2024)

Human microbiota peptides: important roles in human health.

Natural product reports [Epub ahead of print].

Covering: 1974 to 2024Human microbiota consist of a diverse array of microorganisms, such as bacteria, Eukarya, archaea, and viruses, which populate various parts of the human body and live in a cooperatively beneficial relationship with the host. They play a crucial role in supporting the functional balance of the microbiome. The coevolutionary progression has led to the development of specialized metabolites that have the potential to substitute traditional antibiotics in combating global health challenges. Although there has been a lot of research on the human microbiota, there is a considerable lack of understanding regarding the wide range of peptides that these microbial populations produce. Particularly noteworthy are the antibiotics that are uniquely produced by the human microbiome, especially by bacteria, to protect against invasive infections. This review seeks to fill this knowledge gap by providing a thorough understanding of various peptides, along with their in-depth biological importance in terms of human disorders. Advancements in genomics and the understanding of molecular mechanisms that control the interactions between microbiota and hosts have made it easier to find peptides that come from the human microbiome. We hope that this review will serve as a basis for developing new therapeutic approaches and personalized healthcare strategies. Additionally, it emphasizes the significance of these microbiota in the field of natural product discovery and development.

RevDate: 2024-11-15

Saraswat I, A Goel (2024)

Therapeutic Modulation of the Microbiome in Oncology: Current Trends and Future Directions.

Current pharmaceutical biotechnology pii:CPB-EPUB-144539 [Epub ahead of print].

Cancer is a predominant cause of mortality worldwide, necessitating the development of innovative therapeutic techniques. The human microbiome, particularly the gut microbiota, has become a significant element in cancer research owing to its essential role in sustaining health and influencing disease progression. This review examines the microbiome's makeup and essential functions, including immunological modulation and metabolic regulation, which may be evaluated using sophisticated methodologies such as metagenomics and 16S rRNA sequencing. The microbiome influences cancer development by promoting inflammation, modulating the immune system, and producing carcinogenic compounds. Dysbiosis, or microbial imbalance, can undermine the epithelial barrier and facilitate cancer. The microbiome influences chemotherapy and radiation results by modifying drug metabolism, either enhancing or reducing therapeutic efficacy and contributing to side effects and toxicity. Comprehending these intricate relationships emphasises the microbiome's significance in oncology and accentuates the possibility for microbiome-targeted therapeutics. Contemporary therapeutic approaches encompass the utilisation of probiotics and dietary components to regulate the microbiome, enhance treatment efficacy, and minimise unwanted effects. Advancements in research indicate that personalised microbiome-based interventions, have the potential to transform cancer therapy, by providing more effective and customised treatment alternatives. This study aims to provide a comprehensive analysis of the microbiome's influence on the onset and treatment of cancer, while emphasising current trends and future possibilities for therapeutic intervention.

RevDate: 2024-11-14

Wu J, Zeng W, Xie H, et al (2024)

Microbiota-induced alteration of kynurenine metabolism in macrophages drives formation of creeping fat in Crohn's disease.

Cell host & microbe, 32(11):1927-1943.e9.

Hyperplasia of mesenteric tissues in Crohn's disease, called creeping fat (CrF), is associated with surgical recurrence. Although microbiota translocation and colonization have been found in CrF, convincing mouse phenotypes and the underlying mechanisms of CrF formation remain unclear. Utilizing single-nucleus RNA (snRNA) sequencing of CrF and different mouse models, we demonstrate that the commensal Achromobacter pulmonis induces mesenteric adipogenesis through macrophage alteration. Targeted metabolome analysis reveals that L-kynurenine is the most enriched metabolite in CrF. Upregulation of indoleamine 2,3-dioxygenase 1 (IDO1) enhances kynurenine metabolism and drives mesenteric adipogenesis. Leveraging single-cell RNA (scRNA) sequencing of mouse mesenteric tissues and macrophage-specific IDO1 knockout mice, we verify the role of macrophage-sourced L-kynurenine in mesenteric adipogenesis. Mechanistically, L-kynurenine-induced adipogenesis is mediated by the aryl hydrocarbon receptors in adipocytes. Administration of an IDO1 inhibitor or bacteria engineered to degrade L-kynurenine alleviates mesenteric adipogenesis in mice. Collectively, our study demonstrates that microbiota-induced modulation of macrophage metabolism potentiates CrF formation.

RevDate: 2024-11-14

Monzel E, MS Desai (2024)

Bacterial small RNA makes a big impact for gut colonization.

Cell host & microbe, 32(11):1875-1877.

The functions of non-coding small RNAs (sRNAs) within the human microbiome remain largely unexplored. In this Cell Host & Microbe issue, El Mouali et al. identify Segatella RNA colonization factor (SrcF), a sRNA from a prevalent gut bacterium Segatella copri. SrcF promotes colonization of S. copri by regulating bacterial degradation of complex dietary carbohydrates.

RevDate: 2024-11-14
CmpDate: 2024-11-14

Arcimowicz M (2024)

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

Otolaryngologia polska = The Polish otolaryngology, 78(6):1-11.

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

RevDate: 2024-11-14

Efremova I, Alieva A, Maslennikov R, et al (2024)

Akkermansia muciniphila is associated with normal muscle mass and Eggerthella is related with sarcopenia in cirrhosis.

Frontiers in nutrition, 11:1438897.

BACKGROUND: Sarcopenia and gut dysbiosis are common in cirrhosis. The aim is to study the correlations between the gut microbiota taxa and muscle mass level in cirrhosis.

METHODS: The study included 40 cirrhosis patients including 18 patients with sarcopenia. The gut microbiota composition was assessed using amplicon sequencing of the hypervariable V3-V4 regions of the 16S rRNA gene. The skeletal muscle mass, subcutaneous and visceral fat levels were assessed with abdominal computed tomography as skeletal muscle, subcutaneous and visceral fat indices (SMI, SFI and VFI).

RESULTS: Patients with sarcopenia had more relative abundance (RA) of Agathobacter, Anaerostipes, Butyricicoccus, Dorea, Eggerthella, Microbacteriaceae, Veillonella and less RA of Akkermansiaceae, Akkermansia muciniphila, Verrucomicrobiae and Bilophila compared to patients with normal muscle mass. SMI directly correlated with RA of Akkermansia, Alistipes indistinctus, Anaerotruncus, Atopobiaceae, Bacteroides clarus, Bacteroides salyersiae, Barnesiellaceae, Bilophila wadsworthia, Pseudomonadota, Olsenella, and Parabacteroides distasonis, and negatively correlated with RA of Anaerostipes and Eggerthella. Sarcopenia was detected in 20.0% patients whose gut microbiota had Akkermansia but not Eggerthella, and in all the patients, whose gut microbiota had Eggerthella but not Akkermansia. The Akkermansia and Eggerthella abundances were independent determinants of SMI. RA of Akkermansia, Akkermansia muciniphila, Akkermansiaceae, Bacteroides salyersiae, Barnesiella, Bilophila, Desulfobacterota, Verrucomicrobiota and other taxa correlated positively and RA of Anaerovoracaceae, Elusimicrobiaceae, Elusimicrobium, Kiritimatiellae, Spirochaetota, and other taxa correlated negatively with the SFI. RA of Alistripes, Romboutsia, Succinivibrio, and Succinivibrionaceae correlated positively and RA of Bacteroides thetaiotaomicron correlated negatively with VFI.

CONCLUSION: The muscle mass level in cirrhosis correlates with the abundance of several gut microbiota taxa, of which Akkermansia and Eggerthella seems to be the most important.

RevDate: 2024-11-13

Koh H (2024)

A general kernel machine regression framework using principal component analysis for jointly testing main and interaction effects: Applications to human microbiome studies.

NAR genomics and bioinformatics, 6(4):lqae148.

The effect of a treatment on a health or disease response can be modified by genetic or microbial variants. It is the matter of interaction effects between genetic or microbial variants and a treatment. To powerfully discover genetic or microbial biomarkers, it is crucial to incorporate such interaction effects in addition to the main effects. However, in the context of kernel machine regression analysis of its kind, existing methods cannot be utilized in a situation, where a kernel is available but its underlying real variants are unknown. To address such limitations, I introduce a general kernel machine regression framework using principal component analysis for jointly testing main and interaction effects. It begins with extracting principal components from an input kernel through the singular value decomposition. Then, it employs the principal components as surrogate variants to construct three endogenous kernels for the main effects, interaction effects, and both of them, respectively. Hence, it works with a kernel as an input without knowing its underlying real variants, and also detects either the main effects, interaction effects, or both of them robustly. I also introduce its omnibus testing extension to multiple input kernels, named OmniK. I demonstrate its use for human microbiome studies.

RevDate: 2024-11-08

Costa CFFA, Correia-de-Sá T, Araujo R, et al (2024)

The oral-gut microbiota relationship in healthy humans: identifying shared bacteria between environments and age groups.

Frontiers in microbiology, 15:1475159.

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.

RevDate: 2024-11-12

Simbirtseva KY, PW O'Toole (2024)

Healthy and Unhealthy Aging and the Human Microbiome.

Annual review of medicine [Epub ahead of print].

An altered gut microbiome is a feature of many multifactorial diseases, and microbiome effects on host metabolism, immune function, and possibly neurological function are implicated. Increased biological age is accompanied by a change in the gut microbiome. However, age-related health loss does not occur uniformly across all subjects but rather depends on differential loss of gut commensals and gain of pathobionts. In this article, we summarize the known and possible effects of the gut microbiome on the hallmarks of aging and describe the most plausible mechanisms. Understanding and targeting these factors could lead to prolonging health span by rationally maintaining the gut microbiome.

RevDate: 2024-11-12
CmpDate: 2024-11-12

Liu S, Zhang Z, Wang X, et al (2024)

Biosynthetic potential of the gut microbiome in longevous populations.

Gut microbes, 16(1):2426623.

Gut microbiome plays a pivotal role in combating diseases and facilitating healthy aging, and natural products derived from biosynthetic gene clusters (BGCs) of the human microbiome exhibit significant biological activities. However, the natural products of the gut microbiome in long-lived populations remain poorly understood. Here, we integrated six cohorts of long-lived populations, encompassing a total of 1029 fecal metagenomic samples, and employed the metagenomic single sample assembled BGCs (MSSA-BGCs) analysis pipeline to investigate the natural products and their associated species. Our findings reveal that the BGC composition of the extremely long-lived group differed significantly from that of younger elderly and young individuals across five cohorts. Terpene and Type I PKS BGCs were enriched in the extremely long-lived, whereas cyclic-lactone-autoinducer BGCs were more prevalent in the young. Association analysis indicated that terpene BGCs were strongly associated with the abundance of Akkermansia muciniphila, which was also more abundant in the long-lived elderly across at least three cohorts. We assembled 18 A. muciniphila draft genomes using metagenomic data from the extremely long-lived group across six cohorts and discovered that they all harbor two classes of terpene BGCs, which aligns with the 97 complete genomes of A. muciniphila strains retrieved from the NCBI database. The core domains of these two BGC classes are squalene/phytoene synthases involved in the biosynthesis of tri- and tetraterpenes. Furthermore, the abundance of fecal A. muciniphila was significantly associated with eight types of triterpenoids. Targeted terpenoid metabolomic analysis revealed that two triterpenoids, Holstinone C and colubrinic acid, were enriched in the A. muciniphila culture solution compared to the medium, thereby confirming the production of triterpenoids by A. muciniphila. The natural products derived from the gut of long-lived populations provide intriguing indications of their potential beneficial roles in regulating health.

RevDate: 2024-11-11

Feng C, Jia H, Wang H, et al (2024)

MicroNet-MIMRF: a microbial network inference approach based on mutual information and Markov random fields.

Bioinformatics advances, 4(1):vbae167.

MOTIVATION: The human microbiome, comprises complex associations and communication networks among microbial communities, which are crucial for maintaining health. The construction of microbial networks is vital for elucidating these associations. However, existing microbial networks inference methods cannot solve the issues of zero-inflation and non-linear associations. Therefore, necessitating novel methods to improve the accuracy of microbial networks inference.

RESULTS: In this study, we introduce the Microbial Network based on Mutual Information and Markov Random Fields (MicroNet-MIMRF) as a novel approach for inferring microbial networks. Abundance data of microbes are modeled through the zero-inflated Poisson distribution, and the discrete matrix is estimated for further calculation. Markov random fields based on mutual information are used to construct accurate microbial networks. MicroNet-MIMRF excels at estimating pairwise associations between microbes, effectively addressing zero-inflation and non-linear associations in microbial abundance data. It outperforms commonly used techniques in simulation experiments, achieving area under the curve values exceeding 0.75 for all parameters. A case study on inflammatory bowel disease data further demonstrates the method's ability to identify insightful associations. Conclusively, MicroNet-MIMRF is a powerful tool for microbial network inference that handles the biases caused by zero-inflation and overestimation of associations.

The MicroNet-MIMRF is provided at https://github.com/Fionabiostats/MicroNet-MIMRF.

RevDate: 2024-11-07
CmpDate: 2024-11-07

Buytaers FE, Berger N, Van der Heyden J, et al (2024)

The potential of including the microbiome as biomarker in population-based health studies: methods and benefits.

Frontiers in public health, 12:1467121.

The key role of our microbiome in influencing our health status, and its relationship with our environment and lifestyle or health behaviors, have been shown in the last decades. Therefore, the human microbiome has the potential to act as a biomarker or indicator of health or exposure to health risks in the general population, if information on the microbiome can be collected in population-based health surveys or cohorts. It could then be associated with epidemiological participant data such as demographic, clinical or exposure profiles. However, to our knowledge, microbiome sampling has not yet been included as biological evidence of health or exposure to health risks in large population-based studies representative of the general population. In this mini-review, we first highlight some practical considerations for microbiome sampling and analysis that need to be considered in the context of a population study. We then present some examples of topics where the microbiome could be included as biological evidence in population-based health studies for the benefit of public health, and how this could be developed in the future. In doing so, we aim to highlight the benefits of having microbiome data available at the level of the general population, combined with epidemiological data from health surveys, and hence how microbiological data could be used in the future to assess human health. We also stress the challenges that remain to be overcome to allow the use of this microbiome data in order to improve proactive public health policies.

RevDate: 2024-11-07

Liechty ZS, Agans RT, Barbato RA, et al (2024)

Meeting report of the seventh annual Tri-Service Microbiome Consortium Symposium.

BMC proceedings, 18(Suppl 20):25.

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.

RevDate: 2024-11-06

Ji Y, Sun H, Wang Y, et al (2024)

Characterizing the oral and gastrointestinal microbiome associated with healthy aging: insights from long-lived populations in Northeastern China.

GeroScience [Epub ahead of print].

The oral and gastrointestinal (GI) tract microbiota in humans is susceptible to geographical influences and represents vital factors impacting healthy aging. The northeastern region of China, characterized by distinct dietary and climatic conditions, significantly influences the human microbiome composition. However, the microbial structure of the entire long-lived population in this area has not been evaluated. This study recruited a cohort of 142 individuals aged 55-102 residing in Northeast China, and their oral and gut microbiota were evaluated using full-length 16S rRNA gene amplicon sequencing. The results indicate that the oral and GI tract microbiota of long-lived individuals showed reduced microbial taxonomic richness and evenness compared to sub-longevity individuals. With aging, the core species experience a gradual decline in abundance, while subordinate species show an increase. The long-lived population exhibited a heightened ability to enrich beneficial bacteria including Akkermansia, Alistipes, Parabacteroides, and Eubacterium coprostanoligenes in the GI tract, which are associated with host metabolism and have the potential to act as probiotics, reducing the risks of unhealthy aging in the northeast population. Bifidobacterium sp. and Lactobacillus salivarius have been found to coexist in both the oral cavity and the GI tract of long-lived individuals. We hypothesize that beneficial bacterial taxa from the oral cavity colonize the GI tract more extensively in long-lived individuals compared to those with a shorter lifespan. These findings pave the way for identifying probiotic strains that can promote healthy aging in Northeast China.

RevDate: 2024-11-06

Ferrara F, G Valacchi (2024)

Role of microbiota in the GUT-SKIN AXIS responses to outdoor stressors.

Free radical biology & medicine pii:S0891-5849(24)01025-6 [Epub ahead of print].

Beside the respiratory tract, the skin and the gut represent the first defensive lines of our body against the external insults displaying many important biochemical features able to maintain the epithelial barrier integrity and to regulate the tissue immune responses. The human microbiome is essential in maintaining the tissue homeostasis and its dysregulation may lead to tissue conditions including inflammatory pathologies. Among all external insults, air pollutants have been shown to cause oxidative stress damage within the target tissues via an OxInflammatory response. Dysregulation of the gut microbiome (dysbiosis) by outdoor stressors, including air pollutants, may promote the exacerbation of the skin tissue damage via the interplay between the gut-skin axis. The intent of this review is to highlight the ability of exogenous stressors to modulate the human gut-skin axis via a redox regulated mechanism affecting the microbiome and therefore contributing to the development and aggravation of gut and skin conditions.

RevDate: 2024-11-06
CmpDate: 2024-11-06

Chen H, K Chen (2024)

Predicting disease-associated microbes based on similarity fusion and deep learning.

Briefings in bioinformatics, 25(6):.

Increasing studies have revealed the critical roles of human microbiome in a wide variety of disorders. Identification of disease-associated microbes might improve our knowledge and understanding of disease pathogenesis and treatment. Computational prediction of microbe-disease associations would provide helpful guidance for further biomedical screening, which has received lots of research interest in bioinformatics. In this study, a deep learning-based computational approach entitled SGJMDA is presented for predicting microbe-disease associations. Specifically, SGJMDA first fuses multiple similarities of microbes and diseases using a nonlinear strategy, and extracts feature information from homogeneous networks composed of the fused similarities via a graph convolution network. Second, a heterogeneous microbe-disease network is built to further capture the structural information of microbes and diseases by employing multi-neighborhood graph convolution network and jumping knowledge network. Finally, potential microbe-disease associations are inferred through computing the linear correlation coefficients of their embeddings. Results from cross-validation experiments show that SGJMDA outperforms 6 state-of-the-art computational methods. Furthermore, we carry out case studies on three important diseases using SGJMDA, in which 19, 20, and 11 predictions out of their top 20 results are successfully checked by the latest databases, respectively. The excellent performance of SGJMDA suggests that it could be a valuable and promising tool for inferring disease-associated microbes.

RevDate: 2024-11-02
CmpDate: 2024-11-01

Sanches Santos Rizzo Zuttion M, Parimon T, Bora SA, et al (2024)

Antibiotic use during influenza infection augments lung eosinophils that impair immunity against secondary bacterial pneumonia.

The Journal of clinical investigation, 134(21):.

A leading cause of mortality after influenza infection is the development of a secondary bacterial pneumonia. In the absence of a bacterial superinfection, prescribing antibacterial therapies is not indicated but has become a common clinical practice for those presenting with a respiratory viral illness. In a murine model, we found that antibiotic use during influenza infection impaired the lung innate immunologic defenses toward a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA). Antibiotics augment lung eosinophils, which have inhibitory effects on macrophage function through the release of major basic protein. Moreover, we demonstrated that antibiotic treatment during influenza infection caused a fungal dysbiosis that drove lung eosinophilia and impaired MRSA clearance. Finally, we evaluated 3 cohorts of hospitalized patients and found that eosinophils positively correlated with antibiotic use, systemic inflammation, and worsened outcomes. Altogether, our work demonstrates a detrimental effect of antibiotic treatment during influenza infection that has harmful immunologic consequences via recruitment of eosinophils to the lungs, thereby increasing the risk of developing a secondary bacterial infection.

RevDate: 2024-11-01

Kapoor B, Biswas P, Gulati M, et al (2024)

Gut microbiome and Alzheimer's disease: what we know and what remains to be explored.

Ageing research reviews pii:S1568-1637(24)00388-X [Epub ahead of print].

With advancement in human microbiome research, an increasing number of scientific evidences have endorsed the key role of gut microbiota in the pathogenesis of Alzheimer disease. Microbiome dysbiosis, characterized by altered diversity and composition, as well as rise of pathobionts influence not only various gut disorder but also central nervous system disorders such as AD. On the basis of accumulated evidences of past few years now it is quite clear that the gut microbiota can control the functions of the central nervous system (CNS) through the gut-brain axis, which provides a new prospective into the interactions between the gut and brain. The main focus of this review is on the molecular mechanism of the crosstalk between the gut microbiota and the brain through the gut-brain axis, and on the onset and development of neurological disorders triggered by the dysbiosis of gut microbiota. Due to microbiota dysbiosis the permeability of the gut and blood brain barrier is increased which may mediate or affect AD. Along with this, bacterial population of the gut microbiota can secrete amyloid proteins and lipopolysaccharides in a large quantity which may create a disturbance in the signaling pathways and the formation of proinflammatory cytokines associated with the pathogenesis of AD. These topics are followed by a critical analysis of potential intervention strategies targeting gut microbiota dysbiosis, including the use of probiotics, prebiotics, metabolites, diets and fecal microbiota transplantation. The main purpose of this review includes the summarization and discussion on the recent finding that may explain the role of the gut microbiota in the development of AD. Understanding of these fundamental mechanisms may provide a new insight into the novel therapeutic strategies for AD.

RevDate: 2024-10-31

Zheludev IN, Edgar RC, Lopez-Galiano MJ, et al (2024)

Viroid-like colonists of human microbiomes.

Cell pii:S0092-8674(24)01091-2 [Epub ahead of print].

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.

RevDate: 2024-11-01

Mousa WK, Shaikh AY, Ghemrawi R, et al (2024)

Human microbiome derived synthetic antimicrobial peptides with activity against Gram-negative, Gram-positive, and antibiotic resistant bacteria.

RSC medicinal chemistry [Epub ahead of print].

The prevalence of antibacterial resistance has become one of the major health threats of modern times, requiring the development of novel antibacterials. Antimicrobial peptides are a promising source of antibiotic candidates, mostly requiring further optimization to enhance druggability. In this study, a series of new antimicrobial peptides derived from lactomodulin, a human microbiome natural peptide, was designed, synthesized, and biologically evaluated. Within the most active region of the parent peptide, linear peptide LM6 with the sequence LSKISGGIGPLVIPV-NH2 and its cyclic derivatives LM13a and LM13b showed strong antibacterial activity against Gram-positive bacteria, including resistant strains, and Gram-negative bacteria. The peptides were found to have a rapid onset of bactericidal activity and transmission electron microscopy clearly shows the disintegration of the cell membrane, suggesting a membrane-targeting mode of action.

RevDate: 2024-10-31

Lu Z, Mo S, Xie D, et al (2024)

Polyclonal-to-monoclonal transition in colorectal precancerous evolution.

Nature [Epub ahead of print].

Unravelling the origin and evolution of precancerous lesions is crucial for effectively preventing malignant transformation, yet our current knowledge remains limited[1-3]. Here we used a base editor-enabled DNA barcoding system[4] to comprehensively map single-cell phylogenies in mouse models of intestinal tumorigenesis induced by inflammation or loss of the Apc gene. Through quantitative analysis of high-resolution phylogenies including 260,922 single cells from normal, inflamed and neoplastic intestinal tissues, we identified tens of independent cell lineages undergoing parallel clonal expansions within each lesion. We also found polyclonal origins of human sporadic colorectal polyps through bulk whole-exome sequencing and single-gland whole-genome sequencing. Genomic and clinical data support a model of polyclonal-to-monoclonal transition, with monoclonal lesions representing a more advanced stage. Single-cell RNA sequencing revealed extensive intercellular interactions in early polyclonal lesions, but there was significant loss of interactions during monoclonal transition. Therefore, our data suggest that colorectal precancer is often founded by many different lineages and highlight their cooperative interactions in the earliest stages of cancer formation. These findings provide insights into opportunities for earlier intervention in colorectal cancer.

RevDate: 2024-10-31

Collado MC, Devkota S, TS Ghosh (2024)

Gut microbiome: a biomedical revolution.

Nature reviews. Gastroenterology & hepatology [Epub ahead of print].

RevDate: 2024-10-30

Wu J, Zhang S, Chen Y, et al (2023)

Associations between Wastewater Microbiome and Population Smoking Rate Identified Using Wastewater-Based Epidemiology.

Environment & health (Washington, D.C.), 1(6):394-404.

Tobacco use is known to cause health damage, partly by changing the mouth, respiratory tract, and gut-related microbiomes. This study aims to identify the associations between the human microbiome detected in domestic wastewater and the population smoking rate. Metagenomic sequencing and a biomarker discovery algorithm were employed to identify microorganisms as potential microbial biomarkers of smoking through wastewater-based epidemiology. Wastewater samples were collected from selected catchments with low and high smoking rates, i.e., 11.2 ± 1.5% and 17.0 ± 1.6%, respectively. Using the linear discriminant analysis effect size (LEfSe) method, Neisseria, Desulfovibrio, Megamonas, Blautia, Fusicatenibacter, Granulicatella and Enterococcus were suggested as potential biomarker microorganisms. A higher abundance of pathogens, including Neisseria, Eikenella and Haemophilus, was associated with the high smoking rate, likely because of their colonization in smoking-disturbed human guts. The identified potential microbial biomarkers reflect the change of the human gut microbiome due to the long-term smoking behavior. The metagenomic analysis also indicates that smoking upregulates microbial gene expression of genetic information processing, environmental information processing, and cell wall peptidoglycan cleavage, while it downregulates amino acid, lipid, and galactose metabolisms. The findings demonstrate the potential of microbial biomarkers for the surveillance of smoking through a wastewater-based epidemiology approach.

RevDate: 2024-11-01
CmpDate: 2024-10-30

Valiei A, Dickson AM, Aminian-Dehkordi J, et al (2024)

Bacterial community dynamics as a result of growth-yield trade-off and multispecies metabolic interactions toward understanding the gut biofilm niche.

BMC microbiology, 24(1):441.

Bacterial communities are ubiquitous, found in natural ecosystems, such as soil, and within living organisms, like the human microbiome. The dynamics of these communities in diverse environments depend on factors such as spatial features of the microbial niche, biochemical kinetics, and interactions among bacteria. Moreover, in many systems, bacterial communities are influenced by multiple physical mechanisms, such as mass transport and detachment forces. One example is gut mucosal communities, where dense, closely packed communities develop under the concurrent influence of nutrient transport from the lumen and fluid-mediated detachment of bacteria. In this study, we model a mucosal niche through a coupled agent-based and finite-volume modeling approach. This methodology enables us to model bacterial interactions affected by nutrient release from various sources while adjusting individual bacterial kinetics. We explored how the dispersion and abundance of bacteria are influenced by biochemical kinetics in different types of metabolic interactions, with a particular focus on the trade-off between growth rate and yield. Our findings demonstrate that in competitive scenarios, higher growth rates result in a larger share of the niche space. In contrast, growth yield plays a critical role in neutralism, commensalism, and mutualism interactions. When bacteria are introduced sequentially, they cause distinct spatiotemporal effects, such as deeper niche colonization in commensalism and mutualism scenarios driven by species intermixing effects, which are enhanced by high growth yields. Moreover, sub-ecosystem interactions dictate the dynamics of three-species communities, sometimes yielding unexpected outcomes. Competitive, fast-growing bacteria demonstrate robust colonization abilities, yet they face challenges in displacing established mutualistic systems. Bacteria that develop a cooperative relationship with existing species typically obtain niche residence, regardless of their growth rates, although higher growth yields significantly enhance their abundance. Our results underscore the importance of bacterial niche dynamics in shaping community properties and succession, highlighting a new approach to manipulating microbial systems.

RevDate: 2024-10-29

Xie J, Zhang X, Cheng L, et al (2024)

Integrated multi-omics analysis of the microbial profile characteristics associated with pulmonary arterial hypertension in congenital heart disease.

Microbiology spectrum [Epub ahead of print].

Dysregulation of immune and inflammatory cells around blood vessels and metabolic dysfunction are key mechanisms in the development of pulmonary arterial hypertension (PAH). The homeostasis of the human microbiome plays a crucial role in regulating immune responses and the progression of diseases. For pulmonary arterial hypertension associated with congenital heart disease involving body-lung shunt (PAH-CHD), the potential impact of the microbiome on the "gut-lung axis" remains underexplored. This study recruited 15 healthy individuals and 15 patients with pulmonary arterial hypertension due to congenital heart disease from Fuwai Yunnan Hospital, Chinese Academy of Medical Sciences, and Kunming Children's Hospital. We performed differential analyses of metabolites and microbiota from both the gut and lower respiratory tract for these two groups. The goal was to investigate the "gut-lung axis" microbiome and metabolome profiles in children with PAH-CHD and to analyze the interrelationships between these profiles. Ultimately, we aim to propose the potential value of these profiles in aiding diagnosis. The results indicated that the gut and pulmonary microbiota of children with PAH-CHD are characterized by an increased abundance of beneficial symbionts, which are closely linked to changes in the metabolome. Metabolite functional enrichment analysis revealed energy metabolism reprogramming in the PAH-CHD group, with active metabolic pathways associated with bile acid secretion and carnitine homeostasis. Moreover, the differential expression of metabolites was correlated with right heart function and growth development.IMPORTANCEPrevious studies have primarily focused on the relationship between the gut microbiome and PAH. However, the impact of microbial homeostasis on the progression of PAH-CHD from the perspective of the gut-lung axis has not been adequately elucidated. Our study utilizes an integrated multi-omics approach to report on the differential characteristics of gut and lung microbiota between children with PAH-CHD and reference subjects. We found that microbiota influence the pathological changes and disease manifestations of PAH-CHD through their metabolic activity. Additionally, alterations in metabolites impact the microbial ecological structure. Our findings suggest that modulating the microbiome composition may have positive implications for maintaining and regulating the immune environment and pathological progression of PAH-CHD.

RevDate: 2024-10-29

Bouchier C, Touak G, Rei D, et al (2024)

Complete genome sequence of two Christensenella minuta strains CIP 112228 and CIP 112229, isolated from human fecal samples.

Microbiology resource announcements [Epub ahead of print].

Christensenella minuta is one of the representative bacterial species of the human gut microbiome. We report the complete genome sequence of two strains, Christensenella minuta CIP 112228 and CIP 112229, isolated from two healthy volunteers.

RevDate: 2024-10-29

Dumann G, Rohland O, Abdel-Glil MY, et al (2024)

Draft genomes of the bile duct microbiome strains Klebsiella pneumoniae and Enterococcus lactis isolated from bilioenteric drainages with biofilm-forming abilities.

Microbiology resource announcements [Epub ahead of print].

We describe the genetic properties of two strains isolated from the elusive bile duct microbiome from solid organ transplant patients. Bacterial strains Enterococcus lactis (MS-STENT-08-E-001) and Klebsiella pneumoniae (MS-STENT-01-M-001) were isolated from the biofilms of bile duct catheters.

RevDate: 2024-10-29

Toyomane K, Kimura Y, Fukagawa T, et al (2024)

Metagenomic sequencing of CRISPRs as a new marker to aid in personal identification with low-biomass samples.

mSystems [Epub ahead of print].

The high specificity of the human skin microbiome is expected to provide a new marker for personal identification. Metagenomic sequencing of clustered regularly interspaced short palindromic repeats (CRISPRs), which we call metaCRISPR typing, was shown to achieve personal identification accurately. However, the intra-individual variability observed in previous studies, which may be due to poor DNA yields from skin samples, has resulted in non-reproducible results. Furthermore, whether metaCRISPR typing can assist in the forensic human DNA analysis of low-biomass samples, from which the information obtained is insufficient, is unknown. In the present study, we sequenced serially diluted control streptococcal CRISPRs cloned into plasmids to determine the minimum copy number required to obtain reproducible results from metaCRISPR typing. We found that at least 10[2] copies of CRISPRs are necessary to obtain reproducible results. We then analyzed the skin swab samples using both metaCRISPR typing and human DNA typing. When the DNA extracted from the skin swabs was diluted, no information was obtained from six out of eight samples by human DNA typing. On the other hand, beta diversity indices of spacer sequences compared with reference samples were below 0.8 for three out of six samples, for which no information was obtained from human DNA analysis, indicating that the spacers observed in these samples were similar to those in the references. These results indicate that metaCRISPR typing may contribute to the identification of individuals from whom the samples were obtained, even in cases where human DNA yields are insufficient to perform human DNA analysis.IMPORTANCEPrevious studies have developed new personal identification methods utilizing personal differences in the skin microbiome. However, intra-individual diversity of skin microbiome may preclude the application of microbiome-based personal identification. Moreover, no study has compared microbiome-based personal identification and practical human DNA analysis. Here, we revealed that the results of metaCRISPR typing, a previously developed microbiome-based personal identification method, are stable if the copy number of the marker gene is sufficient. We then analyzed the skin swab samples using both metaCRISPR typing and human DNA analysis. Our results indicate that metaCRISPR typing may provide additional information for personal identification using low-biomass samples that cannot be used for conventional human DNA analysis.

RevDate: 2024-10-30
CmpDate: 2024-10-28

Chen H, Huang S, Yao S, et al (2024)

Multi-omics analyses of Bacillus amyloliquefaciens treated mice infected with Schistosoma japonicum reveal dynamics change of intestinal microbiome and its associations with host metabolism.

PLoS neglected tropical diseases, 18(10):e0012583.

BACKGROUND: Schistosomiasis japonica is a serious threat to human health. It causes damage to the intestine and liver. Probiotic therapy has been shown to be effective in alleviating intestinal diseases and improving host health. Previous studies have found that Bacillus amyloliquefaciens could alleviate the pathological symptoms of schistosomiasis japonica, but the regulatory mechanism of alleviating schistosomiasis japonica is still unknown.

PRINCIPAL FINDINGS: This study analyzed the dynamic changes of intestinal microbiome in mice infected with Schistosoma japonicum after the intervention of B. amyloliquefaciens and its connection to host metabolism by multi-omics sequencing technology. B. amyloliquefaciens was found to significantly regulate the homeostasis of intestinal microbiota by promoting the growth of beneficial bacteria and inhibiting potential pathogenic bacteria and protect the number of core microbes. Meanwhile, the genes related to the metabolism of glycerophospholipids and amino acid from intestinal microbiome changed significantly, and were shown to be significantly positively correlated with the associated metabolites of microbial origin. Moreover, host metabolism (lipid metabolism and steroid hormone biosynthesis) was also found to be significantly regulated.

CONCLUSIONS: The recovery of intestinal microbial homeostasis and the regulation of host metabolism revealed the potential probiotic properties of B. amyloliquefaciens, which also provided new ideas for the prevention and adjuvant treatment of schistosomiasis japonica.

RevDate: 2024-10-29

Lam MI, Gleason K, Repp AB, et al (2024)

The spatial and temporal effect of electrochromic windows on indoor and human microbiome in an inpatient hospital.

Antimicrobial stewardship & healthcare epidemiology : ASHE, 4(1):e188.

OBJECTIVE: Improving the hospital environment and developing novel disinfection strategies are critical for infection control in healthcare settings. In this study, we explored the effects of electrochromic (EC) windows on indoor and patient microbiome in an inpatient hospital.

PATIENT AND SETTING: Hematology-Oncology patients at the University of Vermont Medical Center.

METHODS: We conducted a prospective study in ten occupied patient rooms. Five of the patient rooms had active EC windows that tint dynamically to control for heat and glare, and the other five rooms had deactivated EC windows that simulated traditional windows and blinds. Samples were collected one day before patient admission as baseline and on the 1st, 3rd, and 5th day of the patient stay. Total bacterial abundance and bacterial community structure were determined through quantitative PCR and 16s rRNA Illumina MiSeq sequencing, respectively.

RESULTS: Patient rooms with active EC windows had significantly lower light intensity and temperature than traditional patient rooms with blinds. The absolute bacterial abundance and diversities on windows were significantly lower in rooms with EC windows and the bacterial composition changed after one day EC window activation. Compared to baseline, relative abundance of the Staphylococcus genus was significantly lower on EC window surface during the five-day experiment. In contrast, the air microbiome was more diverse in rooms with EC windows.

CONCLUSION: Active electrochromic (EC) windows in patient rooms result in lower light intensity and temperature, reduced bacterial abundance and diversities on window surfaces, and a more diverse air microbiome, informing future healthcare design.

RevDate: 2024-10-28

Toivio L, Launonen H, Lindén J, et al (2024)

Correction: Toivio et al. Ketogenic Diet High in Saturated Fat Promotes Colonic Claudin Expression without Changes in Intestinal Permeability to Iohexol in Healthy Mice. Nutrients 2024, 16, 18.

Nutrients, 16(20):.

Text Correction [...].

RevDate: 2024-10-28

Marangelo C, Vernocchi P, Del Chierico F, et al (2024)

Stratification of Gut Microbiota Profiling Based on Autism Neuropsychological Assessments.

Microorganisms, 12(10):.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Investigations of gut microbiota (GM) play an important role in deciphering disease severity and symptoms. Overall, we stratified 70 ASD patients by neuropsychological assessment, based on Calibrated Severity Scores (CSSs) of the Autism Diagnostic Observation Schedule-Second edition (ADOS-2), Child Behavior Checklist (CBCL) and intelligent quotient/developmental quotient (IQ/DQ) parameters. Hence, metataxonomy and PICRUSt-based KEGG predictions of fecal GM were assessed for each clinical subset. Here, 60% of ASD patients showed mild to moderate autism, while the remaining 40% showed severe symptoms; 23% showed no clinical symptoms, 21% had a risk of behavior problems and 56% had clinical symptoms based on the CBCL, which assesses internalizing problems; further, 52% had no clinical symptoms, 21% showed risk, and 26% had clinical symptoms classified by CBCL externalizing problems. Considering the total CBCL index, 34% showed no clinical symptoms, 13% showed risk, and 52% had clinical symptoms. Here, 70% of ASD patients showed cognitive impairment/developmental delay (CI/DD). The GM of ASDs with severe autism was characterized by an increase in Veillonella, a decrease in Monoglobus pectinilyticus and a higher microbial dysbiosis index (MDI) when compared to mild-moderate ASDs. Patients at risk for behavior problems and showing clinical symptoms were characterized by a GM with an increase of Clostridium, Eggerthella, Blautia, Intestinibacter, Coprococcus, Ruminococcus, Onthenecus and Bariatricus, respectively. Peptidoglycan biosynthesis and biofilm formation KEGGs characterized patients with clinical symptoms, while potential microbiota-activated PPAR-γ-signaling was seen in CI/DD patients. This evidence derived from GM profiling may be used to further improve ASD understanding, leasing to a better comprehension of the neurological phenotype.

RevDate: 2024-10-28

Krause JL, Engelmann B, Lallinger DJD, et al (2024)

Multi-Omics Analysis Unravels the Impact of Stool Sample Logistics on Metabolites and Microbial Composition.

Microorganisms, 12(10):.

Human health and the human microbiome are inevitably intertwined, increasing their relevance in clinical research. However, the collection, transportation and storage of faecal samples may introduce bias due to methodological differences, especially since postal shipping is a common practise in large-scale clinical cohort studies. Using four different Omics layer, we determined the structural (16S rRNA sequencing, cytometric microbiota profiling) and functional integrity (SCFAs, global metabolome) of the microbiota in relation to different easy-to-handle conditions. These conditions were storage at -20 °C, -20 °C as glycerol stock, 4 °C and room temperature with and without oxygen exposure for a maximum of one week. Storage time affected the microbiota on all Omics levels. However, the magnitude was donor-dependent, highlighting the need for purpose-optimized sample collection in clinical multi-donor studies. The effects of oxygen exposure were negligible for all analyses. At ambient temperature, SCFA and compositional profiles were stable for 24 h and 48 h, respectively, while at 4 °C, SCFA profiles were maintained for 48 h. The global metabolome was highly susceptible, already changing at 24 h in non-frozen conditions. Thus, faecal microbiota was best preserved on all levels when transported as a native sample frozen within 24 h, leading to the least biased outcomes in the analysis. We conclude that the immediate freezing of native stool samples for transportation to the lab is best suited for planned multi-Omics analyses that include metabolomics to extend standard sequencing approaches.

RevDate: 2024-10-30
CmpDate: 2024-10-26

Rastegar S, Skurnik M, Tadjrobehkar O, et al (2024)

Synergistic effects of bacteriophage cocktail and antibiotics combinations against extensively drug-resistant Acinetobacter baumannii.

BMC infectious diseases, 24(1):1208.

BACKGROUND: The extensively drug-resistant (XDR) strains of Acinetobacter baumannii have become a major cause of nosocomial infections, increasing morbidity and mortality worldwide. Many different treatments, including phage therapy, are attractive ways to overcome the challenges of antibiotic resistance.

METHODS: This study investigates the biofilm formation ability of 30 XDR A. baumannii isolates and the efficacy of a cocktail of four tempetate bacteriophages (SA1, Eve, Ftm, and Gln) and different antibiotics (ampicillin/sulbactam, meropenem, and colistin) in inhibiting and degrading the biofilms of these strains.

RESULTS: The majority (83.3%) of the strains exhibited strong biofilm formation. The bacteriophage cocktail showed varying degrees of effectiveness against A. baumannii biofilms, with higher concentrations generally leading to more significant inhibition and degradation rates. The antibiotics-bacteriophage cocktail combinations also enhanced the inhibition and degradation of biofilms.

CONCLUSION: The findings suggested that the bacteriophage cocktail is an effective tool in combating A. baumannii biofilms, with its efficacy depending on the concentration. Combining antibiotics with the bacteriophage cocktail improved the inhibition and removal of biofilms, indicating a promising strategy for managing A. baumannii infections. These results contribute to our understanding of biofilm dynamics and the potential of bacteriophage cocktails as a novel therapeutic approach to combat antibiotic-resistant bacteria.

RevDate: 2024-10-27

Otava UE, Tervo L, Havela R, et al (2024)

Phage-Antibiotic Combination Therapy against Recurrent Pseudomonas Septicaemia in a Patient with an Arterial Stent.

Antibiotics (Basel, Switzerland), 13(10):.

Background: Intravascular stent infections are often associated with high risks of morbidity and mortality. We report here a case of a patient with an arterial stent and recurrent Pseudomonas septicaemias successfully treated with phage-meropenem combination therapy. Methods: A 75-year-old female with arteriosclerosis and comorbidities went through a femoropopliteal bypass with prosthesis in the right inguinal area. After the bypass, she developed a recurring Pseudomonas aeruginosa infection and also neutropenia during different antibiotics. A rapidly growing pseudoaneurysm in the right inguinal area led to an emergency intra-arterial stent placement during blood stream infection, later suspected to host a P. aeruginosa biofilm. Removing the stent was deemed precarious, and phage therapy was considered as a compassionate treatment option. A three-phage cocktail infecting the P. aeruginosa strain was prepared and administered intravenously together with meropenem for two weeks, after which, a ten-month follow-up was carried out. Results: No adverse reactions occurred during the phage therapy treatment, while infection markers were normalized. In addition, recovery was seen in a PET-CT scan. During the 10-month follow-up, no further P. aeruginosa septicaemias occurred. Conclusions: Phage-meropenem combination therapy was thus found safe and effective in the treatment of recurrent Pseudomonas septicaemia in a patient with an arterial stent.

RevDate: 2024-10-25
CmpDate: 2024-10-25

Sansonetti PJ, J Doré (2024)

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

Medecine sciences : M/S, 40(10):757-765.

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

RevDate: 2024-10-24

Jia B, Baek JH, Lee JK, et al (2024)

Expanding the β-Lactamase Family in the Human Microbiome.

Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Epub ahead of print].

β-lactams, the most common antibiotics globally, have resistance primarily determined by β-lactamases. Human microbiota and β-lactams influence mutually; however, β-lactamase variety and abundance in the human microbiome remain partially understood. This study aimed to elucidate the diversity, abundance, and substrate spectrum of β-lactamases. 1369 characterized β-lactamases and 16 204 putative sequences are collected from protein databases. Upon clustering analysis and biochemical assays, nine proteins exhibiting less than 35% identity to those previously characterized are confirmed as β-lactamases. These newly identified β-lactamases originated from eight distinct clusters comprising 1163 β-lactamases. Quantifying healthy participants (n = 2394) across 19 countries using functionally confirmed clusters revealed that Japan have the highest gut β-lactamase abundance (log2[reads per million (RPM)] = 6.52) and Fiji have the lowest (log2[RPM] = 2.31). The β-lactamase abundance is correlated with β-lactam consumption (R = 0.50, p = 0.029) and income (R = 0.51, p = 0.024). Comparing individuals with ailments with healthy participants, β-lactamase abundance in the gut is increased significantly in patients with colorectal cancer, cardiovascular diseases, breast cancer, and epilepsy. These outcomes provide insights into investigating antibiotic resistance, antibiotic stewardship, and gut microbiome-antibiotic interactions.

RevDate: 2024-10-30
CmpDate: 2024-10-24

Levi Mortera S, Marzano V, Rapisarda F, et al (2024)

Metaproteomics reveals diet-induced changes in gut microbiome function according to Crohn's disease location.

Microbiome, 12(1):217.

BACKGROUND: Crohn's disease (CD) is characterized by chronic intestinal inflammation. Diet is a key modifiable factor influencing the gut microbiome (GM) and a risk factor for CD. However, the impact of diet modulation on GM function in CD patients is understudied. Herein, we evaluated the effect of a high-fiber, low-fat diet (the Mi-IBD diet) on GM function in CD patients. All participants were instructed to follow the Mi-IBD diet for 8 weeks. One group of CD patients received one-time diet counseling only (Gr1); catered food was supplied for the other three groups, including CD patients (Gr2) and dyads of CD patients and healthy household controls (HHCs) residing within the same household (Gr3-HHC dyads). Stool samples were collected at baseline, week 8, and week 36, and analyzed by liquid chromatography-tandem mass spectrometry.

RESULTS: At baseline, the metaproteomic profiles of CD patients and HHCs differed. The Mi-IBD diet significantly increased carbohydrate and iron transport and metabolism. The predicted microbial composition underlying the metaproteomic changes differed between patients with ileal only disease (ICD) or colonic involvement: ICD was characterized by decreased Faecalibacterium abundance. Even on the Mi-IBD diet, the CD patient metaproteome displayed significant underrepresentation of carbohydrate and purine/pyrimidine synthesis pathways compared to that of HHCs. Human immune-related proteins were upregulated in CD patients compared to HHCs.

CONCLUSIONS: The Mi-IBD diet changed the microbial function of CD patients and enhanced carbohydrate metabolism. Our metaproteomic results highlight functional differences in the microbiome according to disease location. Notably, our dietary intervention yielded the most benefit for CD patients with colonic involvement compared to ileal-only disease. Video Abstract.

RevDate: 2024-10-24

Joos R, Boucher K, Lavelle A, et al (2024)

Examining the healthy human microbiome concept.

Nature reviews. Microbiology [Epub ahead of print].

Human microbiomes are essential to health throughout the lifespan and are increasingly recognized and studied for their roles in metabolic, immunological and neurological processes. Although the full complexity of these microbial communities is not fully understood, their clinical and industrial exploitation is well advanced and expanding, needing greater oversight guided by a consensus from the research community. One of the most controversial issues in microbiome research is the definition of a 'healthy' human microbiome. This concept is complicated by the microbial variability over different spatial and temporal scales along with the challenge of applying a unified definition to the spectrum of healthy microbiome configurations. In this Perspective, we examine the progress made and the key gaps that remain to be addressed to fully harness the benefits of the human microbiome. We propose a road map to expand our knowledge of the microbiome-health relationship, incorporating epidemiological approaches informed by the unique ecological characteristics of these communities.

RevDate: 2024-10-28

Soto Ocaña J, Friedman ES, Keenan O, et al (2024)

Metal availability shapes early life microbial ecology and community succession.

mBio [Epub ahead of print].

The gut microbiota plays a critical role in human health and disease. Microbial community assembly and succession early in life are influenced by numerous factors. In turn, assembly of this microbial community is known to influence the host, including immune system development, and has been linked to outcomes later in life. To date, the role of host-mediated nutritional immunity and metal availability in shaping microbial community assembly and succession early in life has not been explored in depth. Using a human infant cohort, we show that the metal-chelating protein calprotectin is highly abundant in infants. Taxa previously shown to be successful early colonizers of the infant gut, such as Enterococcus, Enterobacteriaceae, and Bacteroides, are highly resistant to experimental metal starvation in culture. Lactobacillus, meanwhile, is highly susceptible to metal restriction, pointing to a possible mechanism by which host-mediated metal limitation shapes the fitness of early colonizing taxa in the infant gut. We further demonstrate that formula-fed infants harbor markedly higher levels of metals in their gastrointestinal tract compared to breastfed infants. Formula-fed infants with high levels of metals harbor distinct microbial communities compared to breastfed infants, with higher levels of Enterococcus, Enterobacter, and Klebsiella, taxa which show increased resistance to the toxic effects of high metal concentrations. These data highlight a new paradigm in microbial community assembly and suggest an unappreciated role for nutritional immunity and dietary metals in shaping the earliest colonization events of the microbiota.IMPORTANCEEarly life represents a critical window for microbial colonization of the human gastrointestinal tract. Surprisingly, we still know little about the rules that govern the successful colonization of infants and the factors that shape the success of early life microbial colonizers. In this study, we report that metal availability is an important factor in the assembly and succession of the early life microbiota. We show that the host-derived metal-chelating protein, calprotectin, is highly abundant in infants and successful early life colonizers can overcome metal restriction. We further demonstrate that feeding modality (breastmilk vs formula) markedly impacts metal levels in the gut, potentially influencing microbial community succession. Our work suggests that metals, a previously unexplored aspect of early life ecology, may play a critical role in shaping the early events of microbiota assembly in infants.

RevDate: 2024-10-23

Weinkove D (2024)

Folates, bacteria and ageing: insights from the model organism C. elegans in the study of nutrition and ageing.

The Proceedings of the Nutrition Society pii:S0029665124004890 [Epub ahead of print].

The relationship between nutrition and ageing is complex. The metabolism and synthesis of micronutrients within the gut microbiome can influence human health but is challenging to study. Furthermore, studying ageing in humans is time-consuming and difficult to control for environmental factors. Studies in model organisms can guide research efforts in this area. This review describes how the nematode Caenorhabditis elegans can be used to study how bacteria and diet influence ageing and inform follow-on studies in humans. It is known that certain bacteria accelerate ageing in C. elegans. This age-accelerating effect is prevented by inhibiting folate synthesis within the bacteria, and we propose that in the human microbiome, certain bacteria also accelerate ageing in a way that can be modulated by interfering with bacterial folate synthesis. Bacterial-derived folates do not promote ageing themselves; rather, ageing is accelerated by bacteria in some way, either through secondary metabolites or other bacterial activity, which is dependent on bacterial folate synthesis. In humans, it may be possible to inhibit bacterial folate synthesis in the human gut while maintaining healthy folate status in the body via food and supplementation. The supplement form of folic acid has a common breakdown product that can be used by bacteria to increase folate synthesis. Thus, supplementation with folic acid may not be good for health in certain circumstances such as in older people or those with an excess of proteobacteria in their microbiome. For these groups, alternative supplement strategies may be a safer way to ensure adequate folate levels.

RevDate: 2024-10-22

Rastegar S, Sabouri S, Tadjrobehkar O, et al (2024)

Characterization of bacteriophage vB_AbaS_SA1 and its synergistic effects with antibiotics against clinical multidrug-resistant Acinetobacter baumannii isolates.

Pathogens and disease pii:7829351 [Epub ahead of print].

Acinetobacter baumannii is a major cause of nosocomial infections globally. The increasing prevalence of multidrug-resistant (MDR) A. baumannii has become an important public health concern. To combat drug resistance, alternative methods such as phage therapy have been suggested. In total, 30 MDR A. baumannii strains were isolated from clinical specimens, and their antibiotic susceptibilities were determined. The Acinetobacter phage vB_AbaS_SA1, isolated from hospital sewage, was characterized. In addition to its plaque size, particle morphology, and host range, its genome sequence was determined and annotated. Finally, the antibacterial effects of phage alone, antibiotics alone, and phage/antibiotic combinations were assessed against the A. baumannii strains. Phage vB_AbaS_SA1 had siphovirus morphology, showed a latent period of 20 minutes, and a 250 PFU/cell (plaque forming unit/cell) burst size. When combined with antibiotics, vB_AbaS_SA1 (SA1) showed a significant phage-antibiotic synergy (PAS) effect and reduced the overall effective concentration of antibiotics in time-kill assessments. The genome of SA1 is a linear double-stranded DNA of 50,108 bp in size with a GC content of 39.15%. Despite the potent antibacterial effect of SA1, it is necessary to perform additional research to completely elucidate the mechanisms of action and potential constraints associated with utilizing this bacteriophage.

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In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

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