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Bibliography on: Human Microbiome

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ESP: PubMed Auto Bibliography 08 Aug 2022 at 01:41 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®)


RevDate: 2022-08-05

Kim K, Lee S, Park SC, et al (2022)

Role of an unclassified Lachnospiraceae in the pathogenesis of type 2 diabetes: a longitudinal study of the urine microbiome and metabolites.

Experimental & molecular medicine [Epub ahead of print].

Recent investigations have revealed that the human microbiome plays an essential role in the occurrence of type 2 diabetes (T2D). However, despite the importance of understanding the involvement of the microbiota throughout the body in T2D, most studies have focused specifically on the intestinal microbiota. Extracellular vesicles (EVs) have been recently found to provide important evidence regarding the mechanisms of T2D pathogenesis, as they act as key messengers between intestinal microorganisms and the host. Herein, we explored microorganisms potentially associated with T2D by tracking changes in microbiota-derived EVs from patient urine samples collected three times over four years. Mendelian randomization analysis was conducted to evaluate the causal relationships among microbial organisms, metabolites, and clinical measurements to provide a comprehensive view of how microbiota can influence T2D. We also analyzed EV-derived metagenomic (N = 393), clinical (N = 5032), genomic (N = 8842), and metabolite (N = 574) data from a prospective longitudinal Korean community-based cohort. Our data revealed that GU174097_g, an unclassified Lachnospiraceae, was associated with T2D (β = -189.13; p = 0.00006), and it was associated with the ketone bodies acetoacetate and 3-hydroxybutyrate (r = -0.0938 and -0.0829, respectively; p = 0.0022 and 0.0069, respectively). Furthermore, a causal relationship was identified between acetoacetate and HbA1c levels (β = 0.0002; p = 0.0154). GU174097_g reduced ketone body levels, thus decreasing HbA1c levels and the risk of T2D. Taken together, our findings indicate that GU174097_g may lower the risk of T2D by reducing ketone body levels.

RevDate: 2022-08-05

Maybee J, Pearson T, L Elliott (2022)

The Gut-Brain-Microbiome Connection: Can Probiotics Decrease Anxiety and Depression?.

Issues in mental health nursing [Epub ahead of print].

Anxiety and depression are highly prevalent mood disorders worldwide. Complete remission of symptoms is often difficult to achieve, despite following recommended treatment guidelines. Numerous antidepressants and anxiolytics exist, and new drugs are being developed constantly, yet the incidence of common mood disorders continues to rise. Despite the prevalence of these issues, mental health treatment has not evolved much in recent years. An exciting area of research uncovered in the past decade is the gut-brain-microbiome axis, a bi-directional communication pathway. Because the human microbiome is closely related to mood, research is being done to investigate whether probiotic supplementation could potentially affect symptoms of anxiety and depression.

RevDate: 2022-08-05

Hakimjavadi H, George SH, Taub M, et al (2022)

The vaginal microbiome is associated with endometrial cancer grade and histology.

Cancer research communications, 2(6):447-455.

The human microbiome has been strongly correlated with disease pathology and outcomes, yet remains relatively underexplored in patients with malignant endometrial disease. In this study, vaginal microbiome samples were prospectively collected at the time of hysterectomy from 61 racially and ethnically diverse patients from three disease conditions: 1) benign gynecologic disease (controls, n=11), 2) low-grade endometrial carcinoma (n=30), and 3) high-grade endometrial carcinoma (n=20). Extracted DNA underwent shotgun metagenomics sequencing, and microbial α and β diversities were calculated. Hierarchical clustering was used to describe community state types (CST), which were then compared by microbial diversity and grade. Differential abundance was calculated, and machine learning utilized to assess the predictive value of bacterial abundance to distinguish grade and histology. Both α- and β-diversity were associated with patient tumor grade. Four vaginal CST were identified that associated with grade of disease. Different histologies also demonstrated variation in CST within tumor grades. Using supervised clustering algorithms, critical microbiome markers at the species level were used to build models that predicted benign vs carcinoma, high-grade carcinoma versus benign, and high-grade versus low-grade carcinoma with high accuracy. These results confirm that the vaginal microbiome segregates not just benign disease from endometrial cancer, but is predictive of histology and grade. Further characterization of these findings in large, prospective studies is needed to elucidate their potential clinical applications.

RevDate: 2022-08-05

Díez López C, Montiel González D, Vidaki A, et al (2022)

Prediction of Smoking Habits From Class-Imbalanced Saliva Microbiome Data Using Data Augmentation and Machine Learning.

Frontiers in microbiology, 13:886201.

Human microbiome research is moving from characterization and association studies to translational applications in medical research, clinical diagnostics, and others. One of these applications is the prediction of human traits, where machine learning (ML) methods are often employed, but face practical challenges. Class imbalance in available microbiome data is one of the major problems, which, if unaccounted for, leads to spurious prediction accuracies and limits the classifier's generalization. Here, we investigated the predictability of smoking habits from class-imbalanced saliva microbiome data by combining data augmentation techniques to account for class imbalance with ML methods for prediction. We collected publicly available saliva 16S rRNA gene sequencing data and smoking habit metadata demonstrating a serious class imbalance problem, i.e., 175 current vs. 1,070 non-current smokers. Three data augmentation techniques (synthetic minority over-sampling technique, adaptive synthetic, and tree-based associative data augmentation) were applied together with seven ML methods: logistic regression, k-nearest neighbors, support vector machine with linear and radial kernels, decision trees, random forest, and extreme gradient boosting. K-fold nested cross-validation was used with the different augmented data types and baseline non-augmented data to validate the prediction outcome. Combining data augmentation with ML generally outperformed baseline methods in our dataset. The final prediction model combined tree-based associative data augmentation and support vector machine with linear kernel, and achieved a classification performance expressed as Matthews correlation coefficient of 0.36 and AUC of 0.81. Our method successfully addresses the problem of class imbalance in microbiome data for reliable prediction of smoking habits.

RevDate: 2022-08-05

Alves-Barroco C, Brito PH, Santos-Sanches I, et al (2022)

Phylogenetic analysis and accessory genome diversity reveal insight into the evolutionary history of Streptococcus dysgalactiae.

Frontiers in microbiology, 13:952110.

Streptococcus dysgalactiae (SD) is capable of infecting both humans and animals and causing a wide range of invasive and non-invasive infections. With two subspecies, the taxonomic status of subspecies of SD remains controversial. Subspecies equisimilis (SDSE) is an important human pathogen, while subspecies dysgalactiae (SDSD) has been considered a strictly animal pathogen; however, occasional human infections by this subspecies have been reported in the last few years. Moreover, the differences between the adaptation of SDSD within humans and other animals are still unknown. In this work, we provide a phylogenomic analysis based on the single-copy core genome of 106 isolates from both the subspecies and different infected hosts (animal and human hosts). The accessory genome of this species was also analyzed for screening of genes that could be specifically involved with adaptation to different hosts. Additionally, we searched putatively adaptive traits among prophage regions to infer the importance of transduction in the adaptation of SD to different hosts. Core genome phylogenetic relationships segregate all human SDSE in a single cluster separated from animal SD isolates. The subgroup of bovine SDSD evolved from this later clade and harbors a specialized accessory genome characterized by the presence of specific virulence determinants (e.g., cspZ) and carbohydrate metabolic functions (e.g., fructose operon). Together, our results indicate a host-specific SD and the existence of an SDSD group that causes human-animal cluster infections may be due to opportunistic infections, and that the exact incidence of SDSD human infections may be underestimated due to failures in identification based on the hemolytic patterns. However, more detailed research into the isolation of human SD is needed to assess whether it is a carrier phenomenon or whether the species can be permanently integrated into the human microbiome, making it ready to cause opportunistic infections.

RevDate: 2022-08-01

Gu W, Moon J, Chisina C, et al (2022)

MiCloud: A unified web platform for comprehensive microbiome data analysis.

PloS one, 17(8):e0272354 pii:PONE-D-22-09539.

The recent advance in massively parallel sequencing has enabled accurate microbiome profiling at a dramatically lowered cost. Then, the human microbiome has been the subject of intensive investigation in public health and medicine. In the meanwhile, researchers have developed lots of microbiome data analysis methods, protocols, and/or tools. Among those, especially, the web platforms can be highlighted because of the user-friendly interfaces and streamlined protocols for a long sequence of analytic procedures. However, existing web platforms can handle only a categorical trait of interest, cross-sectional study design, and the analysis with no covariate adjustment. We therefore introduce here a unified web platform, named MiCloud, for a binary or continuous trait of interest, cross-sectional or longitudinal/family-based study design, and with or without covariate adjustment. MiCloud handles all such types of analyses for both ecological measures (i.e., alpha and beta diversity indices) and microbial taxa in relative abundance on different taxonomic levels (i.e., phylum, class, order, family, genus and species). Importantly, MiCloud also provides a unified analytic protocol that streamlines data inputs, quality controls, data transformations, statistical methods and visualizations with vastly extended utility and flexibility that are suited to microbiome data analysis. We illustrate the use of MiCloud through the United Kingdom twin study on the association between gut microbiome and body mass index adjusting for age. MiCloud can be implemented on either the web server ( or the user's computer (

RevDate: 2022-07-28

Steiner HE, Patterson HK, Giles JB, et al (2022)

Bringing pharmacomicrobiomics to the clinic through well-designed studies.

Clinical and translational science [Epub ahead of print].

Pharmacomicrobiomic studies investigate drug-microbiome interactions, such as the effect of microbial variation on drug response and disposition. Studying and understanding the interactions between the gut microbiome and drugs is becoming increasingly relevant to clinical practice due to its potential for avoiding adverse drug reactions or predicting variability in drug response. The highly variable nature of the human microbiome presents significant challenges to assessing microbes' influence. Studies aiming to explore drug-microbiome interactions should be well designed to account for variation in the microbiome over time and collect data on confounders such as diet, disease, concomitant drugs, and other environmental factors. Here, we assemble a set of important considerations and recommendations for the methodological features required for performing a pharmacomicrobiomic study in humans with a focus on the gut microbiome. Consideration of these factors enable discovery, reproducibility, and more accurate characterization of the relationships between a given drug and the microbiome. Furthermore, appropriate interpretation and dissemination of results from well-designed studies will push the field closer to clinical relevance and implementation.

RevDate: 2022-07-28

Ye P, Qiao X, Tang W, et al (2022)

Testing latent class of subjects with structural zeros in negative binomial models with applications to gut microbiome data.

Statistical methods in medical research [Epub ahead of print].

Human microbiome research has become a hot-spot in health and medical research in the past decade due to the rapid development of modern high-throughput. Typical data in a microbiome study consisting of the operational taxonomic unit counts may have over-dispersion and/or structural zero issues. In such cases, negative binomial models can be applied to address the over-dispersion issue, while zero-inflated negative binomial models can be applied to address both issues. In practice, it is essential to know if there is zero-inflation in the data before applying negative binomial or zero-inflated negative binomial models because zero-inflated negative binomial models may be unnecessarily complex and difficult to interpret, or may even suffer from convergence issues if there is no zero-inflation in the data. On the other hand, negative binomial models may yield invalid inferences if the data does exhibit excessive zeros. In this paper, we develop a new test for detecting zero-inflation resulting from a latent class of subjects with structural zeros in a negative binomial regression model by directly comparing the amount of observed zeros with what would be expected under the negative binomial regression model. A closed form of the test statistic as well as its asymptotic properties are derived based on estimating equations. Intensive simulation studies are conducted to investigate the performance of the new test and compare it with the classical Wald, likelihood ratio, and score tests. The tests are also applied to human gut microbiome data to test latent class in microbial genera.

RevDate: 2022-07-27

Sharon I, Quijada NM, Pasolli E, et al (2022)

The Core Human Microbiome: Does It Exist and How Can We Find It? A Critical Review of the Concept.

Nutrients, 14(14): pii:nu14142872.

The core microbiome, which refers to a set of consistent microbial features across populations, is of major interest in microbiome research and has been addressed by numerous studies. Understanding the core microbiome can help identify elements that lead to dysbiosis, and lead to treatments for microbiome-related health states. However, defining the core microbiome is a complex task at several levels. In this review, we consider the current state of core human microbiome research. We consider the knowledge that has been gained, the factors limiting our ability to achieve a reliable description of the core human microbiome, and the fields most likely to improve that ability. DNA sequencing technologies and the methods for analyzing metagenomics and amplicon data will most likely facilitate higher accuracy and resolution in describing the microbiome. However, more effort should be invested in characterizing the microbiome's interactions with its human host, including the immune system and nutrition. Other components of this holobiontic system should also be emphasized, such as fungi, protists, lower eukaryotes, viruses, and phages. Most importantly, a collaborative effort of experts in microbiology, nutrition, immunology, medicine, systems biology, bioinformatics, and machine learning is probably required to identify the traits of the core human microbiome.

RevDate: 2022-07-27

Rajakaruna S, Pérez-Burillo S, Kramer DL, et al (2022)

Dietary Melanoidins from Biscuits and Bread Crust Alter the Structure and Short-Chain Fatty Acid Production of Human Gut Microbiota.

Microorganisms, 10(7): pii:microorganisms10071268.

Melanoidins are the products of the Maillard reaction between carbonyl and amino groups of macromolecules and are readily formed in foods, especially during heat treatment. In this study we utilized the three-stage Human Gut Simulator system to assess the effect of providing melanoidins extracted from either biscuits or bread crust to the human gut microbiota. Addition of melanoidins to the growth medium led to statistically significant alterations in the microbial community composition, and it increased short-chain fatty acid and antioxidant production by the microbiota. The magnitude of these changes was much higher for cultures grown with biscuit melanoidins. Several lines of evidence indicate that such differences between these melanoidin sources might be due to the presence of lipid components in biscuit melanoidin structures. Because melanoidins are largely not degraded by human gastrointestinal enzymes, they provide an additional source of microbiota-accessible nutrients to our gut microbes.

RevDate: 2022-07-27

Ratanapokasatit Y, Laisuan W, Rattananukrom T, et al (2022)

How Microbiomes Affect Skin Aging: The Updated Evidence and Current Perspectives.

Life (Basel, Switzerland), 12(7): pii:life12070936.

The skin has a multifactorial aging process, caused by both intrinsic and extrinsic factors. A major theory of aging involves cellular senescence or apoptosis resulting from oxidative damage as the skin's antioxidant system tends to weaken with age. The human microbiota is a complex ecosystem that is made up of microorganisms (bacteria, fungi, and viruses). Both gut and skin microbiota have essential roles in the protection against invading pathogens, mediating inflammatory conditions, and the modulation of the immune system which is involved in both innate and adaptive immune responses. However, the human microbiome could be changed during the life stage and affected by various perturbations. An alteration of the intestinal bacteria results in "microbial dysbiosis" which is associated with the influence of various diseases, including aging. The skin interactome is a novel integration of the "genome-microbiome-exposome" that plays a significant role in skin aging and skin health. Mitigating the negative impacts of factors influencing the skin interactome should be the future strategy to protect, prevent, and delay skin aging along with preserving healthy skin conditions. This review summarizes the current evidence on how human microbiomes affect skin aging and demonstrates the possible interventions, relating to human microbiomes, to modulate skin health and aging. Probiotics-based products are currently available mainly for the add-on treatment of many dermatologic conditions. However, at this point, there are limited clinical studies on skin anti-aging purposes and more are required as this evolving concept is on the rise and might provide an insight into future therapeutic options.

RevDate: 2022-07-27

Hua X, Song L, Yu G, et al (2022)

MicrobiomeGWAS: A Tool for Identifying Host Genetic Variants Associated with Microbiome Composition.

Genes, 13(7): pii:genes13071224.

The microbiome is the collection of all microbial genes and can be investigated by sequencing highly variable regions of 16S ribosomal RNA (rRNA) genes. Evidence suggests that environmental factors and host genetics may interact to impact human microbiome composition. Identifying host genetic variants associated with human microbiome composition not only provides clues for characterizing microbiome variation but also helps to elucidate biological mechanisms of genetic associations, prioritize genetic variants, and improve genetic risk prediction. Since a microbiota functions as a community, it is best characterized by β diversity; that is, a pairwise distance matrix. We develop a statistical framework and a computationally efficient software package, microbiomeGWAS, for identifying host genetic variants associated with microbiome β diversity with or without interacting with an environmental factor. We show that the score statistics have positive skewness and kurtosis due to the dependent nature of the pairwise data, which makes p-value approximations based on asymptotic distributions unacceptably liberal. By correcting for skewness and kurtosis, we develop accurate p-value approximations, whose accuracy was verified by extensive simulations. We exemplify our methods by analyzing a set of 147 genotyped subjects with 16S rRNA microbiome profiles from non-malignant lung tissues. Correcting for skewness and kurtosis eliminated the dramatic deviation in the quantile-quantile plots. We provided preliminary evidence that six established lung cancer risk SNPs were collectively associated with microbiome composition for both unweighted (p = 0.0032) and weighted (p = 0.011) UniFrac distance matrices. In summary, our methods will facilitate analyzing large-scale genome-wide association studies of the human microbiome.

RevDate: 2022-07-27

Hajjo R, Sabbah DA, AQ Al Bawab (2022)

Unlocking the Potential of the Human Microbiome for Identifying Disease Diagnostic Biomarkers.

Diagnostics (Basel, Switzerland), 12(7): pii:diagnostics12071742.

The human microbiome encodes more than three million genes, outnumbering human genes by more than 100 times, while microbial cells in the human microbiota outnumber human cells by 10 times. Thus, the human microbiota and related microbiome constitute a vast source for identifying disease biomarkers and therapeutic drug targets. Herein, we review the evidence backing the exploitation of the human microbiome for identifying diagnostic biomarkers for human disease. We describe the importance of the human microbiome in health and disease and detail the use of the human microbiome and microbiota metabolites as potential diagnostic biomarkers for multiple diseases, including cancer, as well as inflammatory, neurological, and metabolic diseases. Thus, the human microbiota has enormous potential to pave the road for a new era in biomarker research for diagnostic and therapeutic purposes. The scientific community needs to collaborate to overcome current challenges in microbiome research concerning the lack of standardization of research methods and the lack of understanding of causal relationships between microbiota and human disease.

RevDate: 2022-07-27

Inchingolo AD, Malcangi G, Semjonova A, et al (2022)

Oralbiotica/Oralbiotics: The Impact of Oral Microbiota on Dental Health and Demineralization: A Systematic Review of the Literature.

Children (Basel, Switzerland), 9(7): pii:children9071014.

The oral microbiota plays a vital role in the human microbiome and oral health. Imbalances between microbes and their hosts can lead to oral and systemic disorders such as diabetes or cardiovascular disease. The purpose of this review is to investigate the literature evidence of oral microbiota dysbiosis on oral health and discuss current knowledge and emerging mechanisms governing oral polymicrobial synergy and dysbiosis; both have enhanced our understanding of pathogenic mechanisms and aided the design of innovative therapeutic approaches as ORALBIOTICA for oral diseases such as demineralization. PubMed, Web of Science, Google Scholar, Scopus, Cochrane Library, EMBEDDED, Dentistry & Oral Sciences Source via EBSCO, APA PsycINFO, APA PsyArticles, and DRUGS@FDA were searched for publications that matched our topic from January 2017 to 22 April 2022, with an English language constraint using the following Boolean keywords: ("microbio*" and "demineralization*") AND ("oral microbiota" and "demineralization"). Twenty-two studies were included for qualitative analysis. As seen by the studies included in this review, the balance of the microbiota is unstable and influenced by oral hygiene, the presence of orthodontic devices in the oral cavity and poor eating habits that can modify its composition and behavior in both positive and negative ways, increasing the development of demineralization, caries processes, and periodontal disease. Under conditions of dysbiosis, favored by an acidic environment, the reproduction of specific bacterial strains increases, favoring cariogenic ones such as Bifidobacterium dentium, Bifidobacterium longum, and S. mutans, than S. salivarius and A. viscosus, and increasing of Firmicutes strains to the disadvantage of Bacteroidetes. Microbial balance can be restored by using probiotics and prebiotics to manage and treat oral diseases, as evidenced by mouthwashes or dietary modifications that can influence microbiota balance and prevent or slow disease progression.

RevDate: 2022-07-25

Lai Y, Mi J, Q Feng (2022)

Fusobacterium nucleatum and Malignant Tumors of the Digestive Tract: A Mechanistic Overview.

Bioengineering (Basel, Switzerland), 9(7): pii:bioengineering9070285.

Fusobacterium nucleatum (F. nucleatum) is an oral anaerobe that plays a role in several oral diseases. However, F. nucleatum is also found in other tissues of the digestive tract, and several studies have recently reported that the level of F. nucleatum is significantly elevated in malignant tumors of the digestive tract. F. nucleatum is proposed as one of the risk factors in the initiation and progression of digestive tract malignant tumors. In this review, we summarize recent reports on F. nucleatum and its role in digestive tract cancers and evaluate the mechanisms underlying the action of F. nucleatum in digestive tract cancers.

RevDate: 2022-07-25

Kitrinos C, Bell RB, Bradley BJ, et al (2022)

Hair Microbiome Diversity within and across Primate Species.

mSystems [Epub ahead of print].

Primate hair and skin are substrates upon which social interactions occur and are host-pathogen interfaces. While human hair and skin microbiomes display body site specificity and immunological significance, little is known about the nonhuman primate (NHP) hair microbiome. Here, we collected hair samples (n = 158) from 8 body sites across 12 NHP species housed at three zoological institutions in the United States to examine the following: (1) the diversity and composition of the primate hair microbiome and (2) the factors predicting primate hair microbiome diversity and composition. If both environmental and evolutionary factors shape the microbiome, then we expect significant differences in microbiome diversity across host body sites, sexes, institutions, and species. We found our samples contained high abundances of gut-, respiratory-, and environment-associated microbiota. In addition, multiple factors predicted microbiome diversity and composition, although host species identity outweighed sex, body site, and institution as the strongest predictor. Our results suggest that hair microbial communities are affected by both evolutionary and environmental factors and are relatively similar across nonhuman primate body sites, which differs from the human condition. These findings have important implications for understanding the biology and conservation of wild and captive primates and the uniqueness of the human microbiome. IMPORTANCE We created the most comprehensive primate hair and skin data set to date, including data from 12 nonhuman primate species sampled from 8 body regions each. We find that the nonhuman primate hair microbiome is distinct from the human hair and skin microbiomes in that it is relatively uniform-as opposed to distinct-across body regions and is most abundant in gut-, environment-, and respiratory-associated microbiota rather than human skin-associated microbiota. Furthermore, we found that the nonhuman primate hair microbiome varies with host species identity, host sex, host environment, and host body site, with host species identity being the strongest predictor. This result demonstrates that nonhuman primate hair microbiome diversity varies with both evolutionary and environmental factors and within and across primate species. These findings have important implications for understanding the biology and conservation of wild and captive primates and the uniqueness of the human microbiome.

RevDate: 2022-07-25

Stuivenberg G, Daisley B, Akouris P, et al (2022)

In vitro assessment of histamine and lactate production by a multi-strain synbiotic.

Journal of food science and technology, 59(9):3419-3427.

Recent studies suggest histamine and d-lactate may negatively impact host health. As excess histamine is deleterious to the host, the identification of bacterial producers has contributed to concerns over the consumption of probiotics or live microorganisms in fermented food items. Some probiotic products have been suspected of inducing d-lactic-acidosis; an illness associated with neurocognitive symptoms such as ataxia. The goals of the present study were to test the in vitro production of histamine and d-lactate by a 24-strain daily synbiotic and to outline methods that others can use to test for their production. Using enzymatic based assays, no significant production of histamine was observed compared to controls (P > 0.05), while d-lactate production was comparable to a commercially available probiotic with no associated health risk. These assays provide a means to add to the safety profile of synbiotic and probiotic products.

RevDate: 2022-07-25

Romani L, Del Chierico F, Macari G, et al (2022)

The Relationship Between Pediatric Gut Microbiota and SARS-CoV-2 Infection.

Frontiers in cellular and infection microbiology, 12:908492.

This is the first study on gut microbiota (GM) in children affected by coronavirus disease 2019 (COVID-19). Stool samples from 88 patients with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and 95 healthy subjects were collected (admission: 3-7 days, discharge) to study GM profile by 16S rRNA gene sequencing and relationship to disease severity. The study group was divided in COVID-19 (68), Non-COVID-19 (16), and MIS-C (multisystem inflammatory syndrome in children) (4). Correlations among GM ecology, predicted functions, multiple machine learning (ML) models, and inflammatory response were provided for COVID-19 and Non-COVID-19 cohorts. The GM of COVID-19 cohort resulted as dysbiotic, with the lowest α-diversity compared with Non-COVID-19 and CTRLs and by a specific β-diversity. Its profile appeared enriched in Faecalibacterium, Fusobacterium, and Neisseria and reduced in Bifidobacterium, Blautia, Ruminococcus, Collinsella, Coprococcus, Eggerthella, and Akkermansia, compared with CTRLs (p < 0.05). All GM paired-comparisons disclosed comparable results through all time points. The comparison between COVID-19 and Non-COVID-19 cohorts highlighted a reduction of Abiotrophia in the COVID-19 cohort (p < 0.05). The GM of MIS-C cohort was characterized by an increase of Veillonella, Clostridium, Dialister, Ruminococcus, and Streptococcus and a decrease of Bifidobacterium, Blautia, Granulicatella, and Prevotella, compared with CTRLs. Stratifying for disease severity, the GM associated to "moderate" COVID-19 was characterized by lower α-diversity compared with "mild" and "asymptomatic" and by a GM profile deprived in Neisseria, Lachnospira, Streptococcus, and Prevotella and enriched in Dialister, Acidaminococcus, Oscillospora, Ruminococcus, Clostridium, Alistipes, and Bacteroides. The ML models identified Staphylococcus, Anaerostipes, Faecalibacterium, Dorea, Dialister, Streptococcus, Roseburia, Haemophilus, Granulicatella, Gemmiger, Lachnospira, Corynebacterium, Prevotella, Bilophila, Phascolarctobacterium, Oscillospira, and Veillonella as microbial markers of COVID-19. The KEGG ortholog (KO)-based prediction of GM functional profile highlighted 28 and 39 KO-associated pathways to COVID-19 and CTRLs, respectively. Finally, Bacteroides and Sutterella correlated with proinflammatory cytokines regardless disease severity. Unlike adult GM profiles, Faecalibacterium was a specific marker of pediatric COVID-19 GM. The durable modification of patients' GM profile suggested a prompt GM quenching response to SARS-CoV-2 infection since the first symptoms. Faecalibacterium and reduced fatty acid and amino acid degradation were proposed as specific COVID-19 disease traits, possibly associated to restrained severity of SARS-CoV-2-infected children. Altogether, this evidence provides a characterization of the pediatric COVID-19-related GM.

RevDate: 2022-07-25

Kantele A, Mero S, T Lääveri (2022)

Doxycycline as an antimalarial: Impact on travellers' diarrhoea and doxycycline resistance among various stool bacteria - Prospective study and literature review.

Travel medicine and infectious disease pii:S1477-8939(22)00149-1 [Epub ahead of print].

BACKGROUND: Antibiotics predispose travellers to acquire multidrug-resistant bacteria, such as extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE). Although widely used in antimalarial prophylaxis, doxycycline has scarcely been studied in this respect.

METHODS: We explored the impact of doxycycline on rates of traveller's diarrhoea (TD), ESBL-PE acquisition and, particularly, doxycycline co-resistance among travel-acquired ESBL-PE in a sample of 412 visitors to low- and middle-income countries. We reviewed the literature on traveller studies of doxycycline/tetracycline resistance among stool pathogens and the impact of doxycycline on TD rates, ESBL-PE acquisition, and doxycycline/tetracycline resistance.

RESULTS: The TD rates were similar for doxycycline users (32/46; 69.6%) and non-users (256/366; 69.9%). Of the 90 travel-acquired ESBL-PE isolates, 84.4% were co-resistant to doxycycline: 100% (11/11) among users and 82.3% (65/79) among non-users. The literature on doxycycline's effect on TD was not conclusive nor did it support a recent decline in doxycycline resistance. Although doxycycline did not increase ESBL-PE acquisition, doxycycline-resistance among stool pathogens proved more frequent for users than non-users.

CONCLUSIONS: Our prospective data and the literature review together suggest the following: 1) doxycycline does not prevent TD; 2) doxycycline use favours acquisition of doxy/tetracycline-co-resistant intestinal bacteria; 3) although doxycycline does not predispose to travel-related ESBL-PE acquisition per se, it selects ESBL-PE strains co-resistant to doxycycline; 4) doxycycline resistance rates are high among stool bacteria in general with no evidence of any tendency to decrease.

RevDate: 2022-07-25

Maarsingh JD, Łaniewski P, MM Herbst-Kralovetz (2022)

Immunometabolic and potential tumor-promoting changes in 3D cervical cell models infected with bacterial vaginosis-associated bacteria.

Communications biology, 5(1):725.

Specific bacteria of the human microbiome influence carcinogenesis at diverse anatomical sites. Bacterial vaginosis (BV) is the most common vaginal disorder in premenopausal women that is associated with gynecologic sequelae, including cervical cancer. BV-associated microorganisms, such as Fusobacterium, Lancefieldella, Peptoniphilus, and Porphyromonas have been associated with gynecologic and other cancers, though the pro-oncogenic mechanisms employed by these bacteria are poorly understood. Here, we integrated a multi-omics approach with our three-dimensional (3-D) cervical epithelial cell culture model to investigate how understudied BV-associated bacteria linked to gynecologic neoplasia influence hallmarks of cancer in vitro. Lancefieldella parvulum and Peptoniphilus lacrimalis elicited robust proinflammatory responses in 3-D cervical cells. Fusobacterium nucleatum and Fusobacterium gonidiaformans modulated metabolic hallmarks of cancer corresponding to accumulation of 2-hydroxyglutarate, pro-inflammatory lipids, and signs of oxidative stress and genotoxic hydrogen sulfide. This study provides mechanistic insights into how gynecologic cancer-associated bacteria might facilitate a tumor-promoting microenvironment in the human cervix.

RevDate: 2022-07-22

Lloréns-Rico V, Simcock JA, Huys GRB, et al (2022)

Single-cell approaches in human microbiome research.

Cell, 185(15):2725-2738.

Microbial culturing and meta-omic profiling technologies have significantly advanced our understanding of the taxonomic and functional variation of the human microbiome and its impact on host processes. The next increase in resolution will come by understanding the role of low-abundant and less-prevalent bacteria and the study of individual cell behaviors that underlie the complexity of microbial ecosystems. To this aim, single-cell techniques are being rapidly developed to isolate, culture, and characterize the genomes and transcriptomes of individual microbes in complex communities. Here, we discuss how these single-cell technologies are providing unique insights into the biology and behavior of human microbiomes.

RevDate: 2022-07-21

Rhoades NS, Cinco IR, Hendrickson SM, et al (2022)

Taxonomic and Functional Shifts in the Perinatal Gut Microbiome of Rhesus Macaques.

Microbiology spectrum [Epub ahead of print].

Pregnancy and the postpartum period result in some of the most dramatic metabolic, hormonal, and physiological changes that can be experienced by an otherwise healthy adult. The timing and magnitude of these changes is key for both maternal and fetal health. One of the factors believed to critically modulate these physiological changes is the maternal gut microbiome. However, the dynamic changes in this community during the perinatal period remain understudied. Clinical studies can be complicated by confounding variables like diet and other drivers of heterogeneity in the human microbiome. Therefore, in this study, we conducted a longitudinal analysis of the fecal microbiome obtained during the pregnancy and postpartum periods in 26 captive rhesus macaques using 16S rRNA gene amplicon sequencing and shotgun metagenomics. Shifts at both the taxonomic and functional potential level were detected when comparing pregnancy to postpartum samples. Taxonomically, Alloprevotella, Actinobacillus, and Anaerovibrio were enriched in the gut microbiome during pregnancy, while Treponema, Lachnospiraceae, and Methanosphaera were more abundant postpartum. Functionally, the gut microbiome during pregnancy was associated with increased abundance in pathways involving the production of the short-chain fatty acid (SCFA) butyrate, while pathways associated with starch degradation and folate transformation were more abundant during the postpartum period. These data demonstrate dramatic changes in the maternal gut microbiome even in the absence of dietary changes and suggest that rhesus macaques could provide a valuable model to determine how changes in the microbiome correlate to other physiological changes in pregnancy. IMPORTANCE Pregnancy and the postpartum period are characterized by a myriad of metabolic and physiological adaptations needed to support fetal growth and maternal health. The maternal gut microbiome is believed to play a key role during this period but remains underexplored. Here, we report significant shifts in the taxonomic landscape and functional potential of the gut microbiome in 26 pregnant rhesus macaques during the transition from pregnancy to the postpartum period, despite shared dietary and environmental exposures. Increased abundance of pathways involved in the production of the short-chain fatty acid butyrate could play a critical role in modulating the maternal immune system and regulating fetal tolerance. On the other hand, increased abundance of pathways associated with starch degradation and folate transformation during the postpartum period could be important for meeting the metabolic demands of breastfeeding and neonatal growth.

RevDate: 2022-07-21

Khan MT, Mahmud A, Hasan M, et al (2022)

Proteome Exploration of Legionella pneumophila To Identify Novel Therapeutics: a Hierarchical Subtractive Genomics and Reverse Vaccinology Approach.

Microbiology spectrum [Epub ahead of print].

Legionella pneumophila is the causative agent of a severe type of pneumonia (lung infection) called Legionnaires' disease. It is emerging as an antibiotic-resistant strain day by day. Hence, identifying novel drug targets and vaccine candidates is essential to fight against this pathogen. Here, attempts were taken through a subtractive genomics approach on the complete proteome of L. pneumophila to address the challenges of multidrug resistance. A total of 2,930 proteins from L. pneumophila proteome were investigated through diverse subtractive proteomics approaches, e.g., identification of human nonhomologous and pathogen-specific essential proteins, druggability and "anti-target" analysis, subcellular localization prediction, human microbiome nonhomology screening, and protein-protein interaction studies to find out effective drug and vaccine targets. Only three fulfilled these criteria and were proposed as novel drug targets against L. pneumophila. Furthermore, outer membrane protein TolB was identified as a potential vaccine target with a better antigenicity score. Antigenicity and transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis, and a molecular docking approach were adopted to generate the most potent epitopes. The final vaccine was constructed by the combination of highly immunogenic epitopes, along with suitable adjuvant and linkers. The designed vaccine construct showed higher binding interaction with different major histocompatibility complex (MHC) molecules and human immune TLR-2 receptors with minimum deformability at the molecular level. The present study aids the development of novel therapeutics and vaccine candidates for efficient treatment and prevention of L. pneumophila infections. However, further wet-lab-based phenotypic and genomic investigations and in vivo trials are highly recommended to validate our prediction experimentally. IMPORTANCE Legionella pneumophila is a human pathogen distributed worldwide, causing Legionnaires' disease (LD), a severe form of pneumonia and respiratory tract infection. L. pneumophila is emerging as an antibiotic-resistant strain, and controlling LD is now difficult. Hence, developing novel drugs and vaccines against L. pneumophila is a major research priority. Here, the complete proteome of L. pneumophila was considered for subtractive genomics approaches to address the challenge of antimicrobial resistance. Our subtractive proteomics approach identified three potential drug targets that are promising for future application. Furthermore, a possible vaccine candidate, "outer membrane protein TolB," was proposed using reverse vaccinology analysis. The constructed vaccine candidate showed higher binding interaction with MHC molecules and human immune TLR-2 receptors at the molecular level. Overall, the present study aids in developing novel therapeutics and vaccine candidates for efficient treatment of the infections caused by L. pneumophila.

RevDate: 2022-07-21

Fabbrocini G, Ferrillo M, Donnarumma M, et al (2022)

A Randomized, Double-Blind, Placebo-Controlled, Multicentric Study to Evaluate the Efficacy and the Tolerability of a Class II Medical Device in the Treatment of Mild and Moderate Acne.

Dermatology and therapy [Epub ahead of print].

INTRODUCTION: Several options are available to treat acne lesions, including topical benzoyl peroxide, topical retinoids, topical antibiotics, oral antibiotics, hormonal therapy, isotretinoin, and procedural therapies, such as light and laser therapies, although these cause side effects. This study aimed to establish the efficacy and tolerability of a class IIa medical device containing lactic acid, azelaic acid/polyglyceryl-3 copolymer, azelamidopropyl dimethyl amine, and bifida ferment lysate for the treatment of mild and moderate acne lesions.

METHODS: A randomized, double-blind, placebo-controlled, multicentric study was carried out in which 60 persons of both genders aged ≥ 16 years affected by mild or moderate acne were enrolled. Each person used the product twice daily for 2 months. The clinical score (classified as absent, mild, moderate, and severe) of lesions such as blackheads, whiteheads, papules and pustules, erythema, desquamation, sebum secretion, and porphyrins production by a wood lamp was evaluated on the basis of a dermatologist's visual assessment at baseline (t0) and after 2 months of treatment (t1), and the results were compared between groups. Digital photographic images were also taken.

RESULTS: Sixty subjects concluded the trial. It was observed that subjects treated with the medical device (group I) showed overall improvement in the analyzed acne lesions compared with placebo (group II) after 2 months of treatment. The efficacy of the treatment was also expressed as partial and total clearance. The medical device produced higher percentages of both partial and total clearance in all analyzed parameters, compared with the placebo group. The study was safe and well tolerated.

CONCLUSIONS: It was observed that the participants showed an overall improvement of the analyzed lesions in comparison with the placebo group, without adverse events during the trial. Hence, the medical device was found to be safe and effective in the treatment of mild or moderate acne.

RevDate: 2022-07-20

Lesniak NA, Schubert AM, Flynn KJ, et al (2022)

The Gut Bacterial Community Potentiates Clostridioides difficile Infection Severity.

mBio [Epub ahead of print].

The severity of Clostridioides difficile infections (CDI) has increased over the last few decades. Patient age, white blood cell count, and creatinine levels as well as C. difficile ribotype and toxin genes have been associated with disease severity. However, it is unclear whether specific members of the gut microbiota are associated with variations in disease severity. The gut microbiota is known to interact with C. difficile during infection. Perturbations to the gut microbiota are necessary for C. difficile to colonize the gut. The gut microbiota can inhibit C. difficile colonization through bile acid metabolism, nutrient consumption, and bacteriocin production. Here, we sought to demonstrate that members of the gut bacterial communities can also contribute to disease severity. We derived diverse gut communities by colonizing germfree mice with different human fecal communities. The mice were then infected with a single C. difficile ribotype 027 clinical isolate, which resulted in moribundity and histopathologic differences. The variation in severity was associated with the human fecal community that the mice received. Generally, bacterial populations with pathogenic potential, such as Enterococcus, Helicobacter, and Klebsiella, were associated with more-severe outcomes. Bacterial groups associated with fiber degradation and bile acid metabolism, such as Anaerotignum, Blautia, Lactonifactor, and Monoglobus, were associated with less-severe outcomes. These data indicate that, in addition to the host and C. difficile subtype, populations of gut bacteria can influence CDI disease severity. IMPORTANCE Clostridioides difficile colonization can be asymptomatic or develop into an infection ranging in severity from mild diarrhea to toxic megacolon, sepsis, and death. Models that predict severity and guide treatment decisions are based on clinical factors and C. difficile characteristics. Although the gut microbiome plays a role in protecting against CDI, its effect on CDI disease severity is unclear and has not been incorporated into disease severity models. We demonstrated that variation in the microbiome of mice colonized with human feces yielded a range of disease outcomes. These results revealed groups of bacteria associated with both severe and mild C. difficile infection outcomes. Gut bacterial community data from patients with CDI could improve our ability to identify patients at risk of developing more severe disease and improve interventions that target C. difficile and the gut bacteria to reduce host damage.

RevDate: 2022-07-19

Ludwig H, Hausmann B, Schreder M, et al (2021)

Reduced alpha diversity of the oral microbiome correlates with short progression-free survival in patients with relapsed/refractory multiple myeloma treated with ixazomib-based therapy (AGMT MM 1, phase II trial).

EJHaem, 2(1):99-103.

Alterations in the human microbiome have been linked to several malignant diseases. Here, we investigated the oral microbiome of 79 patients with relapsed/refractory multiple myeloma (MM) treated with ixazomib-thalidomide-dexamethasone. Increased alpha diversity (Shannon index) at the phylum level was associated with longer progression-free survival (PFS) (10.2 vs 8.5 months, P = .04), particularly in patients with very long (>75% quartile) PFS . Additionally, alpha diversity was lower in patients with progressive disease (P < .05). These findings suggest an interrelationship between the oral microbiome and outcome in patients with MM and encourage a novel direction for diagnostic and/or therapeutic strategies.

RevDate: 2022-07-15

Ksiezarek M, Grosso F, Ribeiro TG, et al (2022)

Genomic diversity of genus Limosilactobacillus.

Microbial genomics, 8(7):.

RevDate: 2022-07-14

Merli P, Massa M, Russo A, et al (2022)

Fecal microbiota transplantation for the treatment of steroid-refractory, intestinal, graft-versus-host disease in a pediatric patient.

RevDate: 2022-07-14

Balaji A, Sapoval N, Seto C, et al (2022)

KOMB: K-core based de novo characterization of copy number variation in microbiomes.

Computational and structural biotechnology journal, 20:3208-3222 pii:S2001-0370(22)00233-1.

Characterizing metagenomes via kmer-based, database-dependent taxonomic classification has yielded key insights into underlying microbiome dynamics. However, novel approaches are needed to track community dynamics and genomic flux within metagenomes, particularly in response to perturbations. We describe KOMB, a novel method for tracking genome level dynamics within microbiomes. KOMB utilizes K-core decomposition to identify Structural variations (SVs), specifically, population-level Copy Number Variation (CNV) within microbiomes. K-core decomposition partitions the graph into shells containing nodes of induced degree at least K, yielding reduced computational complexity compared to prior approaches. Through validation on a synthetic community, we show that KOMB recovers and profiles repetitive genomic regions in the sample. KOMB is shown to identify functionally-important regions in Human Microbiome Project datasets, and was used to analyze longitudinal data and identify keystone taxa in Fecal Microbiota Transplantation (FMT) samples. In summary, KOMB represents a novel graph-based, taxonomy-oblivious, and reference-free approach for tracking CNV within microbiomes. KOMB is open source and available for download at

RevDate: 2022-07-11

Vacca M, Porrelli A, Calabrese FM, et al (2022)

How Metabolomics Provides Novel Insights on Celiac Disease and Gluten-Free Diet: A Narrative Review.

Frontiers in microbiology, 13:859467.

Celiac disease (CD) is an inflammatory autoimmune disorder triggered by the ingestion of gluten from wheat and other cereals. Nowadays, its positive diagnosis is based on invasive approaches such as the histological examination of intestinal biopsies and positive serology screening of antibodies. After proven diagnosis, the only admissible treatment for CD individuals is strict life-long adherence to gluten-free diet (GFD), although it is not a conclusive therapy. Acting by different mechanisms and with different etiologies, both CD and GFD have a great impact on gut microbiota that result in a different taxa composition. Altered production of specific metabolites reflects these microbiota changes. In this light, the currently available literature reports some suggestions about the possible use of specific metabolites, detected by meta-omics analyses, as potential biomarkers for a CD non-invasive diagnosis. To highlight insights about metabolomics application in CD study, we conducted a narrative dissertation of selected original articles published in the last decade. By applying a systematic search, it clearly emerged how the metabolomic signature appears to be contradictory, as well as poorly investigated.

RevDate: 2022-07-10

Johnson KV, L Steenbergen (2022)

Do common antibiotic treatments influence emotional processing?.

Physiology & behavior pii:S0031-9384(22)00206-2 [Epub ahead of print].

Antibiotics are among the most commonly prescribed medications worldwide, yet research in recent years has revealed the detrimental effect they can have on the human microbiome, with implications for health. The community of microorganisms inhabiting the gut has been shown to regulate physiological and neural processes. Since studies in both humans and animal models have revealed that the gut microbiome can affect the brain, influencing emotion and cognition, here we investigate whether antibiotic treatment is associated with changes in emotional processing and mood with a between-subject design in 105 young healthy adult volunteers, using both psychological tests and questionnaires. As both the immune system and vagal signalling can mediate the microbiome-gut-brain axis, we also assess whether there is any evidence of such changes in participant physiology. We find that individuals who have taken antibiotics in the past three months show a stronger emotional bias towards sadness and at a physiological level they have a higher heart rate (though this does not mediate the relationship with negative bias). While we cannot rule out a possible role of prior infection, our findings are in any case highly relevant in light of research revealing that antibiotics are linked to increased susceptibility to depression and anxiety. Our results also have implications for listing antibiotic use as an exclusion criterion in studies on emotional processing and psychophysiology.

RevDate: 2022-07-09

Mukherjee AG, Wanjari UR, Bradu P, et al (2022)

The crosstalk of the human microbiome in breast and colon cancer: A metabolomics analysis.

Critical reviews in oncology/hematology pii:S1040-8428(22)00181-0 [Epub ahead of print].

The human microbiome's role in colon and breast cancer is described in this review. Understanding how the human microbiome and metabolomics interact with breast and colon cancer is the chief area of this study. First, the role of the gut and distal microbiome in breast and colon cancer is investigated, and the direct relationship between microbial dysbiosis and breast and colon cancer is highlighted. This work also focuses on the many metabolomic techniques used to locate prospective biomarkers, make an accurate diagnosis, and research new therapeutic targets for cancer treatment. This review clarifies the influence of anti-tumor medications on the microbiota and the proactive measures that can be taken to treat cancer using a variety of therapies, including radiotherapy, chemotherapy, next-generation biotherapeutics, gene-based therapy, integrated omics technology, and machine learning.

RevDate: 2022-07-09

McKeon MG, Gallant JN, Kim YJ, et al (2022)

It Takes Two to Tango: A Review of Oncogenic Virus and Host Microbiome Associated Inflammation in Head and Neck Cancer.

Cancers, 14(13): pii:cancers14133120.

While the two primary risk factors for head and neck squamous cell carcinoma (HNSCC) are alcohol and tobacco, viruses account for an important and significant upward trend in HNSCC incidence. Human papillomavirus (HPV) is the causative agent for a subset of oropharyngeal squamous cell carcinoma (OPSCC)-a cancer that is impacting a rapidly growing group of typically middle-aged non-smoking white males. While HPV is a ubiquitously present (with about 1% of the population having high-risk oral HPV infection at any one time), less than 1% of those infected with high-risk strains develop OPSCC-suggesting that additional cofactors or coinfections may be required. Epstein-Barr virus (EBV) is a similarly ubiquitous virus that is strongly linked to nasopharyngeal carcinoma (NPC). Both of these viruses cause cellular transformation and chronic inflammation. While dysbiosis of the human microbiome has been associated with similar chronic inflammation and the pathogenesis of mucosal diseases (including OPSCC and NPC), a significant knowledge gap remains in understanding the role of bacterial-viral interactions in the initiation, development, and progression of head and neck cancers. In this review, we utilize the known associations of HPV with OPSCC and EBV with NPC to investigate these interactions. We thoroughly review the literature and highlight how perturbations of the pharyngeal microbiome may impact host-microbiome-tumor-viral interactions-leading to tumor growth.

RevDate: 2022-07-08

Schneider KM, Mohs A, Gui W, et al (2022)

Imbalanced gut microbiota fuels hepatocellular carcinoma development by shaping the hepatic inflammatory microenvironment.

Nature communications, 13(1):3964.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, and therapeutic options for advanced HCC are limited. Here, we observe that intestinal dysbiosis affects antitumor immune surveillance and drives liver disease progression towards cancer. Dysbiotic microbiota, as seen in Nlrp6-/- mice, induces a Toll-like receptor 4 dependent expansion of hepatic monocytic myeloid-derived suppressor cells (mMDSC) and suppression of T-cell abundance. This phenotype is transmissible via fecal microbiota transfer and reversible upon antibiotic treatment, pointing to the high plasticity of the tumor microenvironment. While loss of Akkermansia muciniphila correlates with mMDSC abundance, its reintroduction restores intestinal barrier function and strongly reduces liver inflammation and fibrosis. Cirrhosis patients display increased bacterial abundance in hepatic tissue, which induces pronounced transcriptional changes, including activation of fibro-inflammatory pathways as well as circuits mediating cancer immunosuppression. This study demonstrates that gut microbiota closely shapes the hepatic inflammatory microenvironment opening approaches for cancer prevention and therapy.

RevDate: 2022-07-07

Blum FC, Whitmire JM, Bennett JW, et al (2022)

Nasal microbiota evolution within the congregate setting imposed by military training.

Scientific reports, 12(1):11492.

The human microbiome is comprised of a complex and diverse community of organisms that is subject to dynamic changes over time. As such, cross-sectional studies of the microbiome provide a multitude of information for a specific body site at a particular time, but they fail to account for temporal changes in microbial constituents resulting from various factors. To address this shortcoming, longitudinal research studies of the human microbiome investigate the influence of various factors on the microbiome of individuals within a group or community setting. These studies are vital to address the effects of host and/or environmental factors on microbiome composition as well as the potential contribution of microbiome members during the course of an infection. The relationship between microbial constituents and disease development has been previously explored for skin and soft tissue infections (SSTIs) within congregate military trainees. Accordingly, approximately 25% of the population carries Staphylococcus aureus within their nasal cavity, and these colonized individuals are known to be at increased risk for SSTIs. To examine the evolution of the nasal microbiota of U.S. Army Infantry trainees, individuals were sampled longitudinally from their arrival at Fort Benning, Georgia, until completion of their training 90 days later. These samples were then processed to determine S. aureus colonization status and to profile the nasal microbiota using 16S rRNA gene-based methods. Microbiota stability differed dramatically among the individual trainees; some subjects exhibited great stability, some subjects showed gradual temporal changes and some subjects displayed a dramatic shift in nasal microbiota composition. Further analysis utilizing the available trainee metadata suggests that the major drivers of nasal microbiota stability may be S. aureus colonization status and geographic origin of the trainees. Nasal microbiota evolution within the congregate setting imposed by military training is a complex process that appears to be affected by numerous factors. This finding may indicate that future campaigns to prevent S. aureus colonization and future SSTIs among high-risk military trainees may require a 'personalized' approach.

RevDate: 2022-07-06

Sadrekarimi H, Gardanova ZR, Bakhshesh M, et al (2022)

Emerging role of human microbiome in cancer development and response to therapy: special focus on intestinal microflora.

Journal of translational medicine, 20(1):301.

In recent years, there has been a greater emphasis on the impact of microbial populations inhabiting the gastrointestinal tract on human health and disease. According to the involvement of microbiota in modulating physiological processes (such as immune system development, vitamins synthesis, pathogen displacement, and nutrient uptake), any alteration in its composition and diversity (i.e., dysbiosis) has been linked to a variety of pathologies, including cancer. In this bidirectional relationship, colonization with various bacterial species is correlated with a reduced or elevated risk of certain cancers. Notably, the gut microflora could potentially play a direct or indirect role in tumor initiation and progression by inducing chronic inflammation and producing toxins and metabolites. Therefore, identifying the bacterial species involved and their mechanism of action could be beneficial in preventing the onset of tumors or controlling their advancement. Likewise, the microbial community affects anti-cancer approaches' therapeutic potential and adverse effects (such as immunotherapy and chemotherapy). Hence, their efficiency should be evaluated in the context of the microbiome, underlining the importance of personalized medicine. In this review, we summarized the evidence revealing the microbiota's involvement in cancer and its mechanism. We also delineated how microbiota could predict colon carcinoma development or response to current treatments to improve clinical outcomes.

RevDate: 2022-07-06

Singh S, Natalini JG, LN Segal (2022)

Lung microbial-host interface through the lens of multi-omics.

Mucosal immunology [Epub ahead of print].

In recent years, our understanding of the microbial world within us has been revolutionized by the use of culture-independent techniques. The use of multi-omic approaches can now not only comprehensively characterize the microbial environment but also evaluate its functional aspects and its relationship with the host immune response. Advances in bioinformatics have enabled high throughput and in-depth analyses of transcripts, proteins and metabolites and enormously expanded our understanding of the role of the human microbiome in different conditions. Such investigations of the lower airways have specific challenges but as the field develops, new approaches will be facilitated. In this review, we focus on how integrative multi-omics can advance our understanding of the microbial environment and its effects on the host immune tone in the lungs.

RevDate: 2022-07-05

Mi J, Wang S, Liu P, et al (2022)

CUL4B Upregulates RUNX2 to Promote the Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Epigenetically Repressing the Expression of miR-320c and miR-372/373-3p.

Frontiers in cell and developmental biology, 10:921663 pii:921663.

Mesenchymal stem cells (MSCs) within the periodontal ligament (PDL), termed periodontal ligament stem cells (PDLSCs), have a self-renewing capability and a multidirectional differentiation potential. The molecular mechanisms that regulate multidirectional differentiation, such as the osteogenic differentiation of PDLSCs, remain to be elucidated. Cullin 4B (CUL4B), which assembles the CUL4B-RING ubiquitin ligase (CRL4B) complex, is involved in regulating a variety of developmental and physiological processes including the skeletal development and stemness of cancer stem cells. However, nothing is known about the possible role of CUL4B in the osteogenic differentiation of PDLSCs. Here, we found that knockdown of CUL4B decreased the proliferation, migration, stemness and osteogenic differentiation ability of PDLSCs. Mechanistically, we demonstrate that CUL4B cooperates with the PRC2 complex to repress the expression of miR-320c and miR-372/373-3p, which results in the upregulation of RUNX2, a master transcription factor (TF) that regulates osteogenic differentiation. In brief, the present study reveals the role of CUL4B as a new regulator of osteogenic differentiation in PDLSCs.

RevDate: 2022-07-05

Wang L, Li F, Gu B, et al (2022)

Metaomics in Clinical Laboratory: Potential Driving Force for Innovative Disease Diagnosis.

Frontiers in microbiology, 13:883734.

Currently, more and more studies suggested that reductionism was lack of holistic and integrative view of biological processes, leading to limited understanding of complex systems like microbiota and the associated diseases. In fact, microbes are rarely present in individuals but normally live in complex multispecies communities. With the recent development of a variety of metaomics techniques, microbes could be dissected dynamically in both temporal and spatial scales. Therefore, in-depth understanding of human microbiome from different aspects such as genomes, transcriptomes, proteomes, and metabolomes could provide novel insights into their functional roles, which also holds the potential in making them diagnostic biomarkers in many human diseases, though there is still a huge gap to fill for the purpose. In this mini-review, we went through the frontlines of the metaomics techniques and explored their potential applications in clinical diagnoses of human diseases, e.g., infectious diseases, through which we concluded that novel diagnostic methods based on human microbiomes shall be achieved in the near future, while the limitations of these techniques such as standard procedures and computational challenges for rapid and accurate analysis of metaomics data in clinical settings were also examined.

RevDate: 2022-07-01

Yang S, Wang S, Wang Y, et al (2022)

MB-SupCon: Microbiome-based predictive models via Supervised Contrastive Learning.

Journal of molecular biology pii:S0022-2836(22)00285-6 [Epub ahead of print].

Human microbiome consists of trillions of microorganisms. Microbiota can modulate the host physiology through molecule and metabolite interactions. Integrating microbiome and metabolomics data have the potential to predict different diseases more accurately. Yet, most datasets only measure microbiome data but without paired metabolome data. Here, we propose a novel integrative modeling framework, Microbiome-based Supervised Contrastive Learning Framework (MB-SupCon). MB-SupCon integrates microbiome and metabolome data to generate microbiome embeddings, which can be used to improve the prediction accuracy in datasets that only measure microbiome data. As a proof of concept, we applied MB-SupCon on 720 samples with paired 16S microbiome data and metabolomics data from patients with type 2 diabetes. MB-SupCon outperformed existing prediction methods and achieves high average prediction accuracies for insulin resistance status (84.62%), sex (78.98%), and race (80.04%). Moreover, the microbiome embeddings form separable clusters for different covariate groups in the lower-dimensional space, which enhances data visualization. We also applied MB-SupCon on a large inflammatory bowel disease study and observed similar advantages. Thus, MB-SupCon could be broadly applicable to improve microbiome prediction models in multi-omics disease studies.

RevDate: 2022-07-01

Hong SY, Xia QD, Yang YY, et al (2022)

The role of microbiome: a novel insight into urolithiasis.

Critical reviews in microbiology [Epub ahead of print].

Urolithiasis, referred to as the formation of stones in the urinary tract, is a common disease with growing prevalence and high recurrence rate worldwide. Although researchers have endeavoured to explore the mechanism of urinary stone formation for novel effective therapeutic and preventative measures, the exact aetiology and pathogenesis remain unclear. Propelled by sequencing technologies and culturomics, great advances have been made in understanding the pivotal contribution of the human microbiome to urolithiasis. Indeed, there are diverse and abundant microbes interacting with the host in the urinary tract, overturning the dogma that urinary system, and urine are sterile. The urinary microbiome of stone formers was clearly distinct from healthy individuals. Besides, dysbiosis of the intestinal microbiome appears to be involved in stone formation through the gut-kidney axis. Thus, the human microbiome has potential significant implications for the aetiology of urolithiasis, providing a novel insight into diagnostic, therapeutic, and prognostic strategies. Herein, we review and summarize the landmark microbiome studies in urolithiasis and identify therapeutic implications, challenges, and future perspectives in this rapidly evolving field. To conclude, a new front has opened with the evidence for a microbial role in stone formation, offering potential applications in the prevention, and treatment of urolithiasis.

RevDate: 2022-06-30

Ndika J, Karisola P, Lahti V, et al (2022)

Epigenetic Differences in Long Non-coding RNA Expression in Finnish and Russian Karelia Teenagers With Contrasting Risk of Allergy and Asthma.

Frontiers in allergy, 3:878862.

Background: Previously, we investigated skin microbiota and blood cell gene expression in Finnish and Russian teenagers with contrasting incidence of allergic conditions. The microbiota and transcriptomic signatures were distinctly different, with high Acinetobacter abundance and suppression of genes regulating innate immune response in healthy subjects.

Objective: Here, we investigated long non-coding RNA (lncRNA) expression profiles of blood mononuclear cells (PBMC) from healthy and allergic subjects, to identify lncRNAs that act at the interphase of microbiome-mediated immune homeostasis in allergy/asthma.

Methods: Genome-wide co-expression network analyses of blood cell lncRNA/mRNA expression was integrated with skin microbiota profiles of Finnish (69) and Russian (75) subjects. Selected lncRNAs were validated by stimulation of cohort-derived PBMCs and a macrophage cell model with birch pollen allergen (Betv1) or lipopolysaccharide, respectively.

Results: Finnish and Russian PBMCs were differentiated by 3,818 lncRNA transcripts. In the Finnish subjects with high prevalence of allergy and asthma, a subset of 37 downregulated lncRNAs (including, FAM155A-IT1 and LOC400958) were identified. They were part of a co-expression network with 20 genes known to be related to asthma and allergic rhinitis (R > 0.95). Incidentally, all these 20 genes were also components of pathways corresponding to cellular response to bacterium. The Finnish and Russian samples were also differentiated by the abundance of 176 bacterial OTU (operational taxonomic units). The subset of 37 lncRNAs, associated with allergy, was most correlated with the abundance of Acinetobacter (R > +0.5), Jeotgalicoccus (R > +0.5), Corynebacterium (R < -0.5) and Micrococcus (R < -0.5).

Conclusion: In Finnish and Russian teenagers with contrasting allergy and asthma prevalence, epigenetic differences in lncRNA expression appear to be important components of the underlying microbiota-immune interactions. Unraveling the functions of the 37 differing lncRNAs may be the key to understanding microbiome-immune crosstalk, and to develop clinically relevant biomarkers.

RevDate: 2022-06-29

Kainulainen V, von Schantz-Fant C, Kovanen RM, et al (2022)

Genome-wide siRNA screening reveals several host receptors for the binding of human gut commensal Bifidobacterium bifidum.

NPJ biofilms and microbiomes, 8(1):50.

Bifidobacterium spp. are abundant gut commensals, especially in breast-fed infants. Bifidobacteria are associated with many health-promoting effects including maintenance of epithelial barrier and integrity as well as immunomodulation. However, the protective mechanisms of bifidobacteria on intestinal epithelium at molecular level are poorly understood. In this study, we developed a high-throughput in vitro screening assay to explore binding receptors of intestinal epithelial cells for Bifidobacterium bifidum. Short interfering RNAs (siRNA) were used to silence expression of each gene in the Caco-2 cell line one by one. The screen yielded four cell surface proteins, SERPINB3, LGICZ1, PKD1 and PAQR6, which were identified as potential receptors as the siRNA knock-down of their expression decreased adhesion of B. bifidum to the cell line repeatedly during the three rounds of siRNA screening. Furthermore, blocking of these host cell proteins by specific antibodies decreased the binding of B. bifidum significantly to Caco-2 and HT29 cell lines. All these molecules are located on the surface of epithelial cells and three out of four, SERPINB3, PKD1 and PAQR6, are involved in the regulation of cellular processes related to proliferation, differentiation and apoptosis as well as inflammation and immunity. Our results provide leads to the first steps in the mechanistic cascade of B. bifidum-host interactions leading to regulatory effects in the epithelium and may partly explain how this commensal bacterium is able to promote intestinal homeostasis.

RevDate: 2022-06-28

Farias da Cruz M, Baraúna Magno M, Alves Jural L, et al (2022)

Probiotics and dairy products in dentistry: A bibliometric and critical review of randomized clinical trials.

Food research international (Ottawa, Ont.), 157:111228.

The oral environment is an essential part of the human microbiome. The consumption of probiotic products may improve the oral microbiota and reduce the risk of diseases. This paper presents a bibliometric and critical review of randomized clinical trials (RCTs) that used probiotics to analyze oral parameters in humans. RCTs carried out with no age, gender, and ethnicity restrictions and published in the pre-COVID-19 period were included. Furthermore, the utilization of probiotic dairy products to improve oral health is discussed. The bibliometric review demonstrated that 'Microbiology,' 'Dental caries,' and 'Streptococcus mutants' were the most highlighted keywords. Furthermore, Sweden and India have the highest number of publications. The most prevalent outcomes were 'salivary parameters,' 'periodontal disease,' and 'dental caries.' The most used vehicles for probiotic administration were pharmaceutical formulas and dairy products. The administration of probiotic dairy products could modify the oral microbiota (reductions in S. mutans counts), influence the caries development and periodontal disease in children, adolescents, adults, and the elderly, and improve gingival health. The main probiotic dairy products investigated were milk, fermented milk, yogurt, kefir, curd, and cheese. Lacticaseibacillus paracasei SD1 was the most used probiotic culture. The studies demonstrated that the probiotic effect lasted 2-4 weeks after discontinuing consumption. However, the results depended on the subject type, study design, probiotic strain and concentration, and dairy product type. In conclusion, probiotic dairy products are promising alternatives to improve oral health.

RevDate: 2022-06-27

Kervinen K, Holster T, Saqib S, et al (2022)

Parity and gestational age are associated with vaginal microbiota composition in term and late term pregnancies.

EBioMedicine, 81:104107 pii:S2352-3964(22)00288-2 [Epub ahead of print].

BACKGROUND: Vaginal microbiota and its potential contribution to preterm birth is under intense research. However, only few studies have investigated the vaginal microbiota in later stages of pregnancy or at the onset of labour.

METHODS: We used 16S rRNA gene amplicon sequencing to analyse cross-sectional vaginal swab samples from 324 Finnish women between 37-42 weeks of gestation, sampled before elective caesarean section, at the onset of spontaneous labour, and in pregnancies lasting ≥41 weeks of gestation. Microbiota data were combined with comprehensive clinical data to identify factors associated with microbiota variation.

FINDINGS: Vaginal microbiota composition associated strongly with advancing gestational age and parity, i.e. presence of previous deliveries. Absence of previous deliveries was a strong predictor of Lactobacillus crispatus dominated vaginal microbiota, and the relative abundance of L. crispatus was higher in late term pregnancies, especially among nulliparous women.

INTERPRETATION: This study identified late term pregnancy and reproductive history as factors underlying high abundance of gynaecological health-associated L. crispatus in pregnant women. Our results suggest that the vaginal microbiota affects or reflects the regulation of the duration of gestation and labour onset, with potentially vast clinical utilities. Further studies are needed to address the causality and the mechanisms on how previous labour, but not pregnancy, affects the vaginal microbiota. Parity and gestational age should be accounted for in future studies on vaginal microbiota and reproductive outcomes.

FUNDING: This research was supported by EU H2020 programme Sweet Crosstalk ITN (814102), Academy of Finland, State Research Funding, and University of Helsinki.

RevDate: 2022-06-27

Vernocchi P, Ristori MV, Guerrera S, et al (2022)

Gut Microbiota Ecology and Inferred Functions in Children With ASD Compared to Neurotypical Subjects.

Frontiers in microbiology, 13:871086.

Autism spectrum disorders (ASDs) is a multifactorial neurodevelopmental disorder. The communication between the gastrointestinal (GI) tract and the central nervous system seems driven by gut microbiota (GM). Herein, we provide GM profiling, considering GI functional symptoms, neurological impairment, and dietary habits. Forty-one and 35 fecal samples collected from ASD and neurotypical children (CTRLs), respectively, (age range, 3-15 years) were analyzed by 16S targeted-metagenomics (the V3-V4 region) and inflammation and permeability markers (i.e., sIgA, zonulin lysozyme), and then correlated with subjects' metadata. Our ASD cohort was characterized as follows: 30/41 (73%) with GI functional symptoms; 24/41 (58%) picky eaters (PEs), with one or more dietary needs, including 10/41 (24%) with food selectivity (FS); 36/41 (88%) presenting high and medium autism severity symptoms (HMASSs). Among the cohort with GI symptoms, 28/30 (93%) showed HMASSs, 17/30 (57%) were picky eaters and only 8/30 (27%) with food selectivity. The remaining 11/41 (27%) ASDs without GI symptoms that were characterized by HMASS for 8/11 (72%) and 7/11 (63%) were picky eaters. GM ecology was investigated for the overall ASD cohort versus CTRLs; ASDs with GI and without GI, respectively, versus CTRLs; ASD with GI versus ASD without GI; ASDs with HMASS versus low ASSs; PEs versus no-PEs; and FS versus absence of FS. In particular, the GM of ASDs, compared to CTRLs, was characterized by the increase of Proteobacteria, Bacteroidetes, Rikenellaceae, Pasteurellaceae, Klebsiella, Bacteroides, Roseburia, Lactobacillus, Prevotella, Sutterella, Staphylococcus, and Haemophilus. Moreover, Sutterella, Roseburia and Fusobacterium were associated to ASD with GI symptoms compared to CTRLs. Interestingly, ASD with GI symptoms showed higher value of zonulin and lower levels of lysozyme, which were also characterized by differentially expressed predicted functional pathways. Multiple machine learning models classified correctly 80% overall ASDs, compared with CTRLs, based on Bacteroides, Lactobacillus, Prevotella, Staphylococcus, Sutterella, and Haemophilus features. In conclusion, in our patient cohort, regardless of the evaluation of many factors potentially modulating the GM profile, the major phenotypic determinant affecting the GM was represented by GI hallmarks and patients' age.

RevDate: 2022-06-24

Kelly MS, Bunyavanich S, Phipatanakul W, et al (2022)

The Environmental Microbiome, Allergic Disease and Asthma.

The journal of allergy and clinical immunology. In practice pii:S2213-2198(22)00591-8 [Epub ahead of print].

The environmental microbiome represents the entirety of the microbes and their metabolites that we encounter in our environments. A growing body of evidence supports the role of the environmental microbiome in risk for and severity of allergic diseases and asthma. The environmental microbiome represents a ubiquitous, lifelong exposure to non-self antigens. During the critical window between birth and one year of life, interactions between our early immune system and the environmental microbiome have two consequences: our individual microbiome is populated by environmental microbes, and our immune system is trained regarding which antigens to tolerate. During this time, a diversity of exposures appears largely protective, dramatically decreasing the risk of developing allergic diseases and asthma. As we grow older, our interactions with the environmental microbiome change. While it continues to exert influence over the composition of the human microbiome, the environmental microbiome becomes increasingly a source for antigenic stimulation and infection. The same microbial exposure protective against disease development may exacerbate disease severity. While much has been learned about the importance of the environmental microbiome in allergic disease, much more remains to be understood about these complicated interactions between our environment, our microbiome, our immune system and disease.

RevDate: 2022-06-24

Pang Z, Launonen H, Korpela R, et al (2022)

Local aldosterone synthesis in the large intestine of mouse: An ex vivo incubation study.

The Journal of international medical research, 50(6):3000605221105163.

OBJECTIVE: To investigate the regulation of local aldosterone synthesis by physiological stimulants in the murine gut.

METHODS: Male mice were fed for 14 days with normal, high (1.6%) or low (0.01%) sodium diets. Tissue liver receptor homolog-1 and aldosterone in the colon and caecum were detected using an enzyme-linked immunosorbent assay (ELISA). Released corticosterone and aldosterone in tissue incubation experiments after stimulation with angiotensin II (Ang II) and dibutyryl-cAMP (DBA; the second messenger of adrenocorticotropic hormone) were assayed using an ELISA. Tissue aldosterone synthase (CYP11B2) protein levels were measured using an ELISA and Western blots.

RESULTS: In incubated colon tissues, aldosterone synthase levels were increased by a low-sodium diet; and by Ang II and DBA in the normal diet group. Release of aldosterone into the incubation buffer was increased from the colon by a low-sodium diet and decreased by a high-sodium diet in parallel with changes in aldosterone synthase levels. In mice fed a normal diet, colon incubation with both Ang II and DBA increased the release of aldosterone as well as its precursor corticosterone.

CONCLUSION: Local aldosterone synthesis in the large intestine is stimulated by a low-sodium diet, dibutyryl-cAMP and Ang II similar to the adrenal glands.

RevDate: 2022-06-24

García-Mato E, Martínez-Lamas L, Álvarez-Fernández M, et al (2022)

Molecular Detection of Streptococcus downii sp. nov. from Dental Plaque Samples from Patients with Down Syndrome and Non-Syndromic Individuals.

Microorganisms, 10(6): pii:microorganisms10061098.

A new bacterial species has recently been identified in the dental plaque of an adolescent with Down syndrome. The species is known as Streptococcus downii sp. nov. (abbreviated to S. downii), and it inhibits the growth of S. mutans and certain periodontal pathogens. The aim of this study was to determine the distribution of S. downii in the oral cavity of individuals with Down syndrome. Methods: A specific polymerase chain reaction for the operon of bacteriocin (class IIb lactobin A/cerein 7B family) was designed to detect S. downii in individuals with Down syndrome (n = 200) and in the general population (n = 100). We also compared the whole genome of S. downii and the regions related to its bacteriocins against 127 metagenomes of supragingival plaque of the "Human Microbiome Project". Results: We detected the specific gene of the S. downii bacteriocin in an individual with Down syndrome (Cq, 34.52; GE/μL, 13.0) and in an individual of the non-syndromic control group (Cq, 34.78 Cq; GE/μL, 4.93). The prevalence of S. downii was ≤1% both in Down syndrome and in the general population, which did not allow for clinical-microbiological correlations to be established. This result was confirmed by detecting only one metagenome with an ANIm with approximately 95% homology and with 100% homology with ORFs that code class IIb lactobiocin A/cerein 7B bacteriocins among the 127 metagenomes of the "Human Microbiome Project" tested. Conclusions: The detection rate of S. downii in the supragingival dental plaque was very low, both in the Down syndrome individuals and in the non-syndromic controls. A clinical-microbiological correlation could therefore not be established.

RevDate: 2022-06-24

Graziani C, Laterza L, Talocco C, et al (2022)

Intestinal Permeability and Dysbiosis in Female Patients with Recurrent Cystitis: A Pilot Study.

Journal of personalized medicine, 12(6): pii:jpm12061005.

Recurrent cystitis (RC) is a common disease, especially in females. Anatomical, behavioral and genetic predisposing factors are associated with the ascending retrograde route, which often causes bladder infections. RC seems to be mainly caused by agents derived from the intestinal microbiota, and most frequently by Escherichia coli. Intestinal contiguity contributes to the etiopathogenesis of RC and an alteration in intestinal permeability could have a major role in RC. The aim of this pilot study is to assess gut microbiome dysbiosis and intestinal permeability in female patients with RC. Patients with RC (n = 16) were enrolled and compared with healthy female subjects (n = 15) and patients with chronic gastrointestinal (GI) disorders (n = 238). We calculated the Acute Cystitis Symptom Score/Urinary Tract Infection Symptom Assessment (ACSS/UTISA) and Gastrointestinal Symptom Rating Scale (GSRS) scores and evaluated intestinal permeability and the fecal microbiome in the first two cohorts. Patients with RC showed an increased prevalence of gastrointestinal symptoms compared with healthy controls. Of the patients with RC, 88% showed an increased intestinal permeability with reduced biodiversity of gut microbiota compared to healthy controls, and 68% of the RC patients had a final diagnosis of gastrointestinal disease. Similarly, GI patients reported a higher incidence of urinary symptoms with a diagnosis of RC in 20%. Gut barrier impairment seems to play a major role in the pathogenesis of RC. Further studies are necessary to elucidate the role of microbiota and intestinal permeability in urinary tract infections.

RevDate: 2022-06-24

Guan Z, Q Feng (2022)

Chitosan and Chitooligosaccharide: The Promising Non-Plant-Derived Prebiotics with Multiple Biological Activities.

International journal of molecular sciences, 23(12): pii:ijms23126761.

Biodegradable chitin is the second-most abundant natural polysaccharide, widely existing in the exoskeletons of crabs, shrimps, insects, and the cell walls of fungi. Chitosan and chitooligosaccharide (COS, also named chitosan oligosaccharide) are the two most important deacetylated derivatives of chitin. Compared with chitin, chitosan and COS not only have more satisfactory physicochemical properties but also exhibit additional biological activities, which cause them to be widely applied in the fields of food, medicine, and agriculture. Additionally, due to their significant ability to improve gut microbiota, chitosan and COS are deemed prospective prebiotics. Here, we introduced the production, physicochemical properties, applications, and pharmacokinetic characteristics of chitosan and COS. Furthermore, we summarized the latest research on their antioxidant, anti-inflammatory, and antimicrobial activities. Research progress on the prebiotic functions of chitosan and COS is particularly reviewed. We creatively analyzed and discussed the mechanisms and correlations underlying these activities of chitosan and COS and their physicochemical properties. Our work enriched people's understanding of these non-plant-derived prebiotics. Based on this review, the future directions of research on chitosan and COS are explored. Collectively, optimizing the production technology of chitin derivatives and enriching understanding of their biological functions will shed more light on their capability to improve human health.

RevDate: 2022-06-24

Wu Q, O'Malley J, Datta S, et al (2022)

MarZIC: A Marginal Mediation Model for Zero-Inflated Compositional Mediators with Applications to Microbiome Data.

Genes, 13(6): pii:genes13061049.

BACKGROUND: The human microbiome can contribute to pathogeneses of many complex diseases by mediating disease-leading causal pathways. However, standard mediation analysis methods are not adequate to analyze the microbiome as a mediator due to the excessive number of zero-valued sequencing reads in the data and that the relative abundances have to sum to one. The two main challenges raised by the zero-inflated data structure are: (a) disentangling the mediation effect induced by the point mass at zero; and (b) identifying the observed zero-valued data points that are not zero (i.e., false zeros).

METHODS: We develop a novel marginal mediation analysis method under the potential-outcomes framework to address the issues. We also show that the marginal model can account for the compositional structure of microbiome data.

RESULTS: The mediation effect can be decomposed into two components that are inherent to the two-part nature of zero-inflated distributions. With probabilistic models to account for observing zeros, we also address the challenge with false zeros. A comprehensive simulation study and the application in a real microbiome study showcase our approach in comparison with existing approaches.

CONCLUSIONS: When analyzing the zero-inflated microbiome composition as the mediators, MarZIC approach has better performance than standard causal mediation analysis approaches and existing competing approach.

RevDate: 2022-06-24

Grada A, Ghannoum MA, CG Bunick (2022)

Sarecycline Demonstrates Clinical Effectiveness against Staphylococcal Infections and Inflammatory Dermatoses: Evidence for Improving Antibiotic Stewardship in Dermatology.

Antibiotics (Basel, Switzerland), 11(6): pii:antibiotics11060722.

Tetracycline class antibiotics are widely used for multiple skin diseases, including acne vulgaris, acne rosacea, cutaneous infections, inflammatory dermatoses, and autoimmune blistering disorders. Concerns about antibiotic resistance and protecting the human/host microbiome beg the question whether broad-spectrum tetracyclines such as doxycycline and minocycline should be prescribed at such a high rate by dermatologists when a narrow-spectrum tetracycline derivative, sarecycline, exists. We evaluated the clinical effectiveness of oral sarecycline against cutaneous staphylococcal infections, eyelid stye, and mucous membrane pemphigoid to determine whether sarecycline is a viable option for clinicians to practice improved antibiotic stewardship. We observed significant improvement in staphylococcal infections and inflammatory dermatoses with courses of oral sarecycline as short as 9 days, with no reported adverse events. These clinical findings are consistent with in vitro microbiological data and anti-inflammatory properties of sarecycline. Our data provides a strong rationale for clinicians to use narrow-spectrum sarecycline rather than broad-spectrum tetracyclines as a first-line agent in treating staphylococcal skin infections and inflammatory skin diseases for which tetracyclines are currently commonly employed. Such advancement in the practice paradigm in dermatology will enhance antibiotic stewardship, reduce risk of antibiotic resistance, protect the human microbiome, and provide patients with precision medicine care.

RevDate: 2022-06-23

Cani PD, Depommier C, Derrien M, et al (2022)

Author Correction: Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms.

RevDate: 2022-06-22

Sharp C, KR Foster (2022)

Host control and the evolution of cooperation in host microbiomes.

Nature communications, 13(1):3567.

Humans, and many other species, are host to diverse symbionts. It is often suggested that the mutual benefits of host-microbe relationships can alone explain cooperative evolution. Here, we evaluate this hypothesis with evolutionary modelling. Our model predicts that mutual benefits are insufficient to drive cooperation in systems like the human microbiome, because of competition between symbionts. However, cooperation can emerge if hosts can exert control over symbionts, so long as there are constraints that limit symbiont counter evolution. We test our model with genomic data of two bacterial traits monitored by animal immune systems. In both cases, bacteria have evolved as predicted under host control, tending to lose flagella and maintain butyrate production when host-associated. Moreover, an analysis of bacteria that retain flagella supports the evolution of host control, via toll-like receptor 5, which limits symbiont counter evolution. Our work puts host control mechanisms, including the immune system, at the centre of microbiome evolution.

RevDate: 2022-06-21

Dai W, Li C, Li T, et al (2022)

Super-taxon in human microbiome are identified to be associated with colorectal cancer.

BMC bioinformatics, 23(1):243.

BACKGROUND: Microbial communities in the human body, also known as human microbiota, impact human health, such as colorectal cancer (CRC). However, the different roles that microbial communities play in healthy and disease hosts remain largely unknown. The microbial communities are typically recorded through the taxa counts of operational taxonomic units (OTUs). The sparsity and high correlations among OTUs pose major challenges for understanding the microbiota-disease relation. Furthermore, the taxa data are structured in the sense that OTUs are related evolutionarily by a hierarchical structure.

RESULTS: In this study, we borrow the idea of super-variant from statistical genetics, and propose a new concept called super-taxon to exploit hierarchical structure of taxa for microbiome studies, which is essentially a combination of taxonomic units. Specifically, we model a genus which consists of a set of OTUs at low hierarchy and is designed to reflect both marginal and joint effects of OTUs associated with the risk of CRC to address these issues. We first demonstrate the power of super-taxon in detecting highly correlated OTUs. Then, we identify CRC-associated OTUs in two publicly available datasets via a discovery-validation procedure. Specifically, four species of two genera are found to be associated with CRC: Parvimonas micra, Parvimonas sp., Peptostreptococcus stomatis, and Peptostreptococcus anaerobius. More importantly, for the first time, we report the joint effect of Parvimonas micra and Parvimonas sp. (p = 0.0084) as well as that of Peptostrepto-coccus stomatis and Peptostreptococcus anaerobius (p = 8.21e-06) on CRC. The proposed approach provides a novel and useful tool for identifying disease-related microbes by taking the hierarchical structure of taxa into account and further sheds new lights on their potential joint effects as a community in disease development.

CONCLUSIONS: Our work shows that proposed approaches are effective to study the microbiota-disease relation taking into account for the sparsity, hierarchical and correlated structure among microbes.

RevDate: 2022-06-21

Zhang L, Jonscher KR, Zhang Z, et al (2022)

Islet autoantibody seroconversion in type-1 diabetes is associated with metagenome-assembled genomes in infant gut microbiomes.

Nature communications, 13(1):3551.

The immune system of some genetically susceptible children can be triggered by certain environmental factors to produce islet autoantibodies (IA) against pancreatic β cells, which greatly increases their risk for Type-1 diabetes. An environmental factor under active investigation is the gut microbiome due to its important role in immune system education. Here, we study gut metagenomes that are de-novo-assembled in 887 at-risk children in the Environmental Determinants of Diabetes in the Young (TEDDY) project. Our results reveal a small set of core protein families, present in >50% of the subjects, which account for 64% of the sequencing reads. Time-series binning generates 21,536 high-quality metagenome-assembled genomes (MAGs) from 883 species, including 176 species that hitherto have no MAG representation in previous comprehensive human microbiome surveys. IA seroconversion is positively associated with 2373 MAGs and negatively with 1549 MAGs. Comparative genomics analysis identifies lipopolysaccharides biosynthesis in Bacteroides MAGs and sulfate reduction in Anaerostipes MAGs as functional signatures of MAGs with positive IA-association. The functional signatures in the MAGs with negative IA-association include carbohydrate degradation in lactic acid bacteria MAGs and nitrate reduction in Escherichia MAGs. Overall, our results show a distinct set of gut microorganisms associated with IA seroconversion and uncovered the functional genomics signatures of these IA-associated microorganisms.

RevDate: 2022-06-20

Smith G, Manzano Marín A, Reyes-Prieto M, et al (2022)

Human follicular mites: Ectoparasites becoming symbionts.

Molecular biology and evolution pii:6604544 [Epub ahead of print].

Most humans carry mites in the hair follicles of their skin for their entire lives. Follicular mites are the only metazoans tha continuously live on humans. We propose that Demodex folliculorum (Acari) represents a transitional stage from a host-injuring obligate parasite to an obligate symbiont. Here, we describe the profound impact of this transition on the genome and physiology of the mite. Genome sequencing revealed that the permanent host association of D. folliculorum led to an extensive genome reduction through relaxed selection and genetic drift, resulting in the smallest number of protein-coding genes yet identified among panarthropods. Confocal microscopy revealed that this gene loss coincided with an extreme reduction in the number of cells. Single uninucleate muscle cells are sufficient to operate each of the three segments that form each walking leg. While it has been assumed that the reduction of the cell number in parasites starts early in development, we identified a greater total number of cells in the last developmental stage (nymph) than in the terminal adult stage, suggesting that reduction starts at the adult or ultimate stage of development. This is the first evolutionary step in an arthropod species adopting a reductive, parasitic or endosymbiotic lifestyle. Somatic nuclei show underreplication at the diploid stage. Novel eye structures or photoreceptors as well as a unique human host melatonin-guided day/night rhythm are proposed for the first time. The loss of DNA repair genes coupled with extreme endogamy might have set this mite species on an evolutionary dead-end trajectory.

RevDate: 2022-06-20

Anonymous (2022)

Retraction: Human microbiome and homeostasis: Insights into the key role of prebiotics, probiotics, and symbiotics.

RevDate: 2022-06-20

Yoon YC, Ahn BH, Min JW, et al (2022)

Stimulatory Effects of Extracellular Vesicles Derived from Leuconostoc holzapfelii That Exists in Human Scalp on Hair Growth in Human Follicle Dermal Papilla Cells.

Current issues in molecular biology, 44(2):845-866 pii:cimb44020058.

Human hair follicle dermal papilla cells (HFDPCs) located in hair follicles (HFs) play a pivotal role in hair follicle morphogenesis, hair cycling, and hair growth. Over the past few decades, probiotic bacteria (PB) have been reported to have beneficial effects such as improved skin health, anti-obesity, and immuno-modulation for conditions including atopic dermatitis and inflammatory bowel disease (IBD). PB can secrete 50~150 nm sized extracellular vesicles (EVs) containing microbial DNA, miRNA, proteins, lipids, and cell wall components. These EVs can regulate communication between bacteria or between bacteria and their host. Although numerous biological effects of PB-EVs have been reported, the physiological roles of Leuconostoc holzapfelii (hs-Lh), which is isolated from human scalp tissue, and the extracellular vesicles derived from them (hs-LhEVs) are largely unknown. Herein, we investigated the effects of hs-LhEVs on hair growth in HFDPCs. We show that hs-LhEVs increase cell proliferation, migration, and regulate the cell cycle. Furthermore, hs-LhEVs were found to modulate the mRNA expression of hair-growth-related genes in vitro. These data demonstrate that hs-LhEVs can reduce apoptosis by modulating the cell cycle and promote hair growth by regulation via the Wnt/β-catenin signal transduction pathway.

RevDate: 2022-06-20

Jo CS, Myung CH, Yoon YC, et al (2022)

The Effect of Lactobacillus plantarum Extracellular Vesicles from Korean Women in Their 20s on Skin Aging.

Current issues in molecular biology, 44(2):526-540 pii:cimb44020036.

Extracellular vesicles, which are highly conserved in most cells, contain biologically active substances. The vesicles and substances interact with cells and impact physiological mechanisms. The skin is the most external organ and is in direct contact with the external environment. Photoaging and skin damage are caused by extrinsic factors. The formation of wrinkles is a major indicator of skin aging and is caused by a decrease in collagen and hyaluronic acid. MMP-1 expression is also increased. Due to accruing damage, skin aging reduces the ability of the skin barrier, thereby lowering the skin's ability to contain water and increasing the amount of water loss. L. plantarum suppresses various harmful bacteria by secreting an antimicrobial substance. L. plantarum is also found in the skin, and research on the interactions between the bacteria and the skin is in progress. Although several studies have investigated L. plantarum, there are only a limited number of studies on extracellular vesicles (EV) derived from L. plantarum, especially in relation to skin aging. Herein, we isolated EVs that were secreted from L. plantarum of women in their 20s (LpEVs). We then investigated the effect of LpEVs on skin aging in CCD986sk. We showed that LpEVs modulated the mRNA expression of ECM related genes in vitro. Furthermore, LpEVs suppressed wrinkle formation and pigmentation in clinical trials. These results demonstrated that LpEVs have a great effect on skin aging by regulating ECM related genes. In addition, our study offers important evidence on the depigmentation effect of LpEVs.

RevDate: 2022-06-21
CmpDate: 2022-06-21

Krawczyk KT, Locht C, M Kowalewicz-Kulbat (2022)

Halophilic Archaea Halorhabdus Rudnickae and Natrinema Salaciae Activate Human Dendritic Cells and Orient T Helper Cell Responses.

Frontiers in immunology, 13:833635.

Halophilic archaea are procaryotic organisms distinct from bacteria, known to thrive in hypersaline environments, including salt lakes, salterns, brines and salty food. They have also been identified in the human microbiome. The biological significance of halophiles for human health has rarely been examined. The interactions between halophilic archaea and human dendritic cells (DCs) and T cells have not been identified so far. Here, we show for the first time that the halophilic archaea Halorhabdus rudnickae and Natrinema salaciae activate human monocyte-derived DCs, induce DC maturation, cytokine production and autologous T cell activation. In vitro both strains induced DC up-regulation of the cell-surface receptors CD86, CD80 and CD83, and cytokine production, including IL-12p40, IL-10 and TNF-α, but not IL-23 and IL-12p70. Furthermore, autologous CD4+ T cells produced significantly higher amounts of IFN-γ and IL-13, but not IL-17A when co-cultured with halophile-stimulated DCs in comparison to T cells co-cultured with unstimulated DCs. IFN-γ was almost exclusively produced by naïve T cells, while IL-13 was produced by both naïve and memory CD4+ T cells. Our findings thus show that halophilic archaea are recognized by human DCs and are able to induce a balanced cytokine response. The immunomodulatory functions of halophilic archaea and their potential ability to re-establish the immune balance may perhaps participate in the beneficial effects of halotherapies.

RevDate: 2022-06-19

Juarez VM, Montalbine AN, A Singh (2022)

Microbiome as an immune regulator in health, disease, and therapeutics.

Advanced drug delivery reviews pii:S0169-409X(22)00290-3 [Epub ahead of print].

New discoveries in drugs and drug delivery systems are focused on identifying and delivering a pharmacologically effective agent, potentially targeting a specific molecular component. However, current drug discovery and therapeutic delivery approaches do not necessarily exploit the complex regulatory network of an indispensable microbiota that has been engineered through evolutionary processes in humans or has been altered by environmental exposure or diseases. The human microbiome, in all its complexity, plays an integral role in the maintenance of host functions such as metabolism and immunity. However, dysregulation in this intricate ecosystem has been linked with a variety of diseases, ranging from inflammatory bowel disease to cancer. Therapeutics and bacteria have an undeniable effect on each other and understanding the interplay between microbes and drugs could lead to new therapies, or to changes in how existing drugs are delivered. In addition, targeting the human microbiome using engineered therapeutics has the potential to address global health challenges. Here, we present the challenges and cutting-edge developments in microbiome-immune cell interactions and outline novel targeting strategies to advance drug discovery and therapeutics, which are defining a new era of personalized and precision medicine.

RevDate: 2022-06-18

Shetty SA, Kostopoulos I, Geerlings SY, et al (2022)

Dynamic metabolic interactions and trophic roles of human gut microbes identified using a minimal microbiome exhibiting ecological properties.

The ISME journal [Epub ahead of print].

Microbe-microbe interactions in the human gut are influenced by host-derived glycans and diet. The high complexity of the gut microbiome poses a major challenge for unraveling the metabolic interactions and trophic roles of key microbes. Synthetic minimal microbiomes provide a pragmatic approach to investigate their ecology including metabolic interactions. Here, we rationally designed a synthetic microbiome termed Mucin and Diet based Minimal Microbiome (MDb-MM) by taking into account known physiological features of 16 key bacteria. We combined 16S rRNA gene-based composition analysis, metabolite measurements and metatranscriptomics to investigate community dynamics, stability, inter-species metabolic interactions and their trophic roles. The 16 species co-existed in the in vitro gut ecosystems containing a mixture of complex substrates representing dietary fibers and mucin. The triplicate MDb-MM's followed the Taylor's power law and exhibited strikingly similar ecological and metabolic patterns. The MDb-MM exhibited resistance and resilience to temporal perturbations as evidenced by the abundance and metabolic end products. Microbe-specific temporal dynamics in transcriptional niche overlap and trophic interaction network explained the observed co-existence in a competitive minimal microbiome. Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem.

RevDate: 2022-06-17

Shaffer JP, Carpenter CS, Martino C, et al (2022)

A comparison of six DNA extraction protocols for 16S, ITS and shotgun metagenomic sequencing of microbial communities.

BioTechniques [Epub ahead of print].

Microbial communities contain a broad phylogenetic diversity of organisms; however, the majority of methods center on describing bacteria and archaea. Fungi are important symbionts in many ecosystems and are potentially important members of the human microbiome, beyond those that can cause disease. To expand our analysis of microbial communities to include data from the fungal internal transcribed spacer (ITS) region, five candidate DNA extraction kits were compared against our standardized protocol for describing bacteria and archaea using 16S rRNA gene amplicon- and shotgun metagenomics sequencing. The results are presented considering a diverse panel of host-associated and environmental sample types and comparing the cost, processing time, well-to-well contamination, DNA yield, limit of detection and microbial community composition among protocols. Across all criteria, the MagMAX Microbiome kit was found to perform best. The PowerSoil Pro kit performed comparably but with increased cost per sample and overall processing time. The Zymo MagBead, NucleoMag Food and Norgen Stool kits were included.

RevDate: 2022-06-21
CmpDate: 2022-06-17

Ley R (2022)

The human microbiome: there is much left to do.

Nature, 606(7914):435.

RevDate: 2022-06-14

Anipindi M, D Bitetto (2022)

Diagnostic and Therapeutic Uses of the Microbiome in the Field of Oncology.

Cureus, 14(5):e24890.

Cancer is a leading cause of death worldwide and it can affect almost every part of the human body. Effective screening and early diagnosis of cancers is extremely difficult due to the multifactorial etiology of the disease and delayed presentation of the patients. The available treatments are usually not specific to the affected organ system, leading to intolerable systemic side effects and early withdrawal from therapies. In vivo and in vitro studies have revealed an association of specific microbiome signatures with individual cancers. The cancer-related human microbiome has also been shown to affect the response of tissues to chemotherapy, immunotherapy, and radiation. This is an excellent opportunity for us to design specific screening markers using the microbiome to prevent cancers and diagnose them early. We can also develop precise treatments that can target cancer-affected specific organ systems and probably use a lesser dose of chemotherapy or radiation for the same effect. This prevents adverse effects and early cessation of treatments. However, we need further studies to exactly clarify and characterize these associations. In this review article, we focus on the association of the microbiome with individual cancers and highlight its future role in cancer screenings, diagnosis, prognosis, and treatments.

RevDate: 2022-06-13

Laÿna D, Jannel R, CDD Rupprecht (2022)

Living through multispecies societies: Approaching the microbiome with Imanishi Kinji.

Endeavour pii:S0160-9327(22)00014-X [Epub ahead of print].

Recent research about the microbiome points to a picture in which we, humans, are 'living through' nature, and nature itself is living in us. Our bodies are hosting-and depend on-the multiple species that constitute human microbiota. This article will discuss current research on the microbiome through the ideas of Japanese ecologist Imanishi Kinji (1902-1992). First, some of Imanishi's key ideas regarding the world of living beings and multispecies societies are presented. Second, seven types of relationships concerning the human microbiome, human beings, and the environment are explored. Third, inspired by Imanishi's work, this paper develops the idea of dynamic, porous, and complex multispecies societies in which different living beings or species are codependent on others, including microbiota and human beings.

RevDate: 2022-06-13

Swafford AD, Khandelwal S, S Bhute (2021)

Potential Immune-Microbiome Interactions in Breast Cancer May Advance Treatment: What's Holding Us Back?.

Critical reviews in immunology, 41(6):27-42.

The impact of the human microbiome, the diverse collection of microorganisms that inhabit nearly every niche in the human body, in shaping the immune response to dysbiotic events is apparent if poorly understood, particularly in complex, evolving disease states such as breast cancer. The impacts can be both indirect via metabolites and immune-interactions along the skin, gut, and oral cavities where the microbial communities are most abundant, or direct in the tumor microenvironment where microbial activities can promote growth or clearance of cancerous cells. Based on reports of using gut microbial signatures to predict therapeutic efficacy, the role that gut microbes and their metabolites may play in shaping the success or failure of immunotherapy has been extensively reviewed. In this review, we dissect the evidence for the direct and distal impact of microbes on oncogenesis, tumor growth and the immune responses to combat or promote tolerance of breast cancer tumors. Implementation of robust, valid analyses and methods are lacking in the field, and we provide recommendations for researchers and clinicians to work together to characterize the micro-biome-immune-breast cancer interactions that will hopefully enable the next generation of biomarkers and targets for improving disease outcomes.

RevDate: 2022-06-13

Maslinska M, Kostyra-Grabczak K, Królicki L, et al (2021)

The Role of the Microbiome in Sjogren's Syndrome.

Critical reviews in immunology, 41(6):13-26.

The human microbiome is a living ecosystem existing within the host organism, determined by a balance between pathogenic microorganisms, symbionts, and commensals. The disturbance of microbiome composition-dysbiosis-often resulting in the excess of commensal numbers, may push the immune system towards activation of inflammatory and autoimmune processes. Changes in the microbiome of gut, eyes, and mouth may play a significant role in the development and course of autoimmune diseases, including primary Sjogren's syndrome. This autoimmune disease is associated with changes in the protective barrier of the epithelium, which is an important part of the antimicrobial defense. The development of pSS may be influenced by a mechanism of molecular mimicry between microbial antigens and self antigens leading to the initiation of anti-Ro60 antibody response. The knowledge of the influence of the state of microbiome on pSS may translate into the prophylaxis of the progression of dryness symptoms. The aim of this review is to present various aspects related to the human microbiome and Sjogren's syndrome.

RevDate: 2022-06-13

Passos GA, VK Chaturvedi (2021)

Preface Special Issue: Microbiome-Immune System Interactions.

Critical reviews in immunology, 41(6):v.

Body homeostasis, immune response to microbial infections or vaccination, control of cancer onset or autoimmune or inflammatory diseases, as well as autism or other behavioral disorders, among other examples, are now recognized to be associated with the complex constitution of the body's microbiome. Recent findings demonstrate that the microbial composition, i.e., pathogenic, symbionts, and commensal viruses, bacteria, or yeast mainly in the gut, is strongly associated with susceptibility/resistance to several classes of diseases or its therapeutic response. This Special Issue focuses on the processes that link the human microbiome to three classes of diseases; immunodeficiency, autoimmunity, and cancer. Review articles cover aspects of the recent progress in selective immunoglobulin A (IgA) deficiency, Sjörgren's syndrome, breast cancer.

RevDate: 2022-06-13

Ene A, Stegman N, Wolfe A, et al (2022)

Genomic insights into Lactobacillus gasseri and Lactobacillus paragasseri.

PeerJ, 10:e13479 pii:13479.

Background: Antimicrobial and antifungal species are essential members of the healthy human microbiota. Several different species of lactobacilli that naturally inhabit the human body have been explored for their probiotic capabilities including strains of the species Lactobacillus gasseri. However, L. gasseri (identified by 16S rRNA gene sequencing) has been associated with urogenital symptoms. Recently a new sister taxon of L. gasseri was described: L. paragasseri. L. paragasseri is also posited to have probiotic qualities.

Methods: Here, we present a genomic investigation of all (n = 79) publicly available genome assemblies for both species. These strains include isolates from the vaginal tract, gastrointestinal tract, urinary tract, oral cavity, wounds, and lungs.

Results: The two species cannot be distinguished from short-read sequencing of the 16S rRNA as the full-length gene sequences differ only by two nucleotides. Based upon average nucleotide identity (ANI), we identified 20 strains deposited as L. gasseri that are in fact representatives of L. paragasseri. Investigation of the genic content of the strains of these two species suggests recent divergence and/or frequent gene exchange between the two species. The genomes frequently harbored intact prophage sequences, including prophages identified in strains of both species. To further explore the antimicrobial potential associated with both species, genome assemblies were examined for biosynthetic gene clusters. Gassericin T and S were identified in 46 of the genome assemblies, with all L. paragasseri strains including one or both bacteriocins. This suggests that the properties once ascribed to L. gasseri may better represent the L. paragasseri species.

RevDate: 2022-06-13

Ozma MA, Abbasi A, Akrami S, et al (2022)

Postbiotics as the key mediators of the gut microbiota-host interactions.

Le infezioni in medicina, 30(2):180-193 pii:1124-9390_30_2_2022_180-193.

The priority of the Sustainable Development Goals for 2022 is to reduce all causes related to mortality. In this regard, microbial bioactive compounds with characteristics such as optimal compatibility and close interaction with the host immune system are considered a novel therapeutic approach. The fermentation process is one of the most well-known pathways involved in the natural synthesis of a diverse range of postbiotics. However, some postbiotics are a type of probiotic response behavior to environmental stimuli that usually play well-known biological roles. Also, postbiotics with unique structure and function are key mediators between intestinal microbiota and host cellular processes/metabolic pathways that play a significant role in maintaining homeostasis. By further understanding the nature of parent microbial cells, factors affecting their metabolic pathways, and the development of compatible extraction and identification methods, it is possible to achieve certain formulations of postbiotics with special efficiencies, which in turn will significantly improve the performance of health systems (especially in developing countries) toward a wide range of acute/chronic diseases. The present review aims to describe the fundamental role of postbiotics as the key mediators of the microbiota-host interactions. Besides, it presents the available current evidence regarding the interaction between postbiotics and host cells through potential cell receptors, stimulation/improvement of immune system function, and the enhancement of the composition and function of the human microbiome.

RevDate: 2022-06-12

Song WJ, Kang WY, Liu XM, et al (2022)

[Study on the dynamic changes of oral microbiota in type 2 diabetes patients with periodontitis after initial periodontal therapy].

Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology, 57(6):585-594.

Objectives: To clarify the effect of initial periodontal therapy on the dynamic changes of oral (saliva, dorsal tongue and subgingival plaque) microbiota in periodontitis patients with or without type 2 diabetes mellitus (T2DM). Methods: A total of 14 patients with chronic periodontitis (CP group) and 14 CP patients with T2DM (CP-T2DM group) were included from Department of Periodontology, School and Hospital of Stomatology,Cheeloo College of Medicine, Shandong University. The microbial samples were collected from saliva, dorsal tongue and subgingival plaque of first molars at baseline, 1.5 and 3 months after initial periodontal therapy, and were detected by 16S rRNA (V3-V4 region) gene sequencing. The sequencing data were analyzed to obtain microbial distribution and community structure information. The same professional periodontist evaluated the periodontal status of patients according to periodontitis detection indices before and after initial periodontal therapy. Meanwhile, patients' blood samples were collected and related metabolic indices were evaluated. Results: After initial periodontal therapy, the glycosylated hemoglobin levels [(7.46±1.69)%] in CP-T2DM group were significantly improved than that at baseline [(7.65±1.34)%] (t=0.52,P=0.610). The probing depth of the sampling sites [CP group: (2.94±0.46) mm, CP-T2DM group: (2.95±0.35) mm] and bleeding index (CP group: 1.91±0.42, CP-T2DM group: 1.67±0.49) at 3 months after treatment were significantly decreased than the probing depth [CP group: (3.99±0.77) mm, CP-T2DM group: (3.80±0.76) mm] (F=25.61, P<0.001; F=17.63, P<0.001) and bleeding index (CP group: 3.03±0.52, CP-T2DM group: 2.54±0.65) (F=28.43, P<0.001; F=20.21, P<0.001) at baseline. The flora analysis showed that the α and β diversity indices of the same sites in the CP and CP-T2DM groups did not change significantly before and after the initial therapy, but the bacterial abundance at each site changed. There were commonalities and differences in the microbial composition of each site in the CP and CP-T2DM groups. Among them, the relative abundance of Proteobacteria in saliva and dorsal tongue samples of the two groups after treatment was basically consistent with the change trend in the subgingival plaque microbes. In the subgingival plaque of the CP group, the relative abundance of Proteobacteria showed a gradual increase with the prolongation of initial periodontal therapy; while in the CP-T2DM group, it showed a trend of first increase and then decrease. Syntrophy, Dethiosulfate, Methanobacteriaceae and TG5 in CP and CP-T2DM groups were all significantly dominant bacteria in subgingival plaque at baseline (P<0.05). Moreover, in the CP-T2DM group Spirochetes also showed a significant advantage. At 1.5 months after treatment, Rhizobacteria, Alcaligenes, Comamomons, Delftia, Blautella, etc. were dominant in subgingival plaque (P<0.05). Firmicutes, Clostridia/Clostridiales, Enterococci and Ruminococci showed significant differences at 3 months (P<0.05). Conclusions: Plaques in saliva and tongue dorsal could reflect the effects of initial periodontal therapy on the dynamic changes of microorganisms to a certain extent. CP and CP-T2DM patients had differences in microbial composition and responses to initial periodontal therapy.

RevDate: 2022-06-11

Mills JG, Selway CA, Thomas T, et al (2022)

Schoolyard Biodiversity Determines Short-Term Recovery of Disturbed Skin Microbiota in Children.

Microbial ecology [Epub ahead of print].

Creating biodiverse urban habitat has been proposed, with growing empirical support, as an intervention for increasing human microbial diversity and reducing associated diseases. However, ecological understanding of urban biodiversity interventions on human skin microbiota remains limited. Here, we experimentally test the hypotheses that disturbed skin microbiota recover better in outdoor schoolyard environments and that greater biodiversity provides a greater response. Repeating the experiment three times, we disturbed skin microbiota of fifty-seven healthy 10-to-11-year-old students with a skin swab (i.e., cleaning), then exposed them to one school environment-either a 'classroom' (n = 20), 'sports field' (n = 14), or biodiverse 'forest' (n = 23)-for 45 min. Another skin swab followed the exposure to compare 'before' and 'after' microbial communities. After 45 min, the disturbance immediately followed by outdoor exposure, especially the 'forest', had an enriching and diversifying effect on skin microbiota, while 'classroom' exposure homogenised inter-personal variability. Each effect compounded over consecutive days indicating longer-term exposure outcomes. The experimental disturbance also reduced the core skin microbiota, and only outdoor environments were able to replenish lost species richness to core membership (n species > 50% prevalent). Overall, we find that environmental setting, especially including biodiversity, is important in human microbiota recovery periods and that the outdoors provide resilience to skin communities. This work also has implications for the inclusion of short periods of outside or forest exposure in school scheduling. Future investigations of the health impacts of permanent urban biodiversity interventions are needed.

RevDate: 2022-06-11

Diociaiuti A, Giancristoforo S, Calò Carducci FI, et al (2022)

Auricular leishmaniasis in a child successfully treated with intralesional amphotericin B.

Pediatric dermatology [Epub ahead of print].

Cutaneous leishmaniasis (CL) is the most frequent form of leishmaniasis. The auricle is an extremely rare site for CL in the Old World. Auricular CL may be mistaken for other entities, such as relapsing polychondritis (RP). Here we report a pediatric case of Old World auricular CL mimicking RP in a child successfully treated with intralesional liposomal amphotericin B.

RevDate: 2022-06-10

Chen Y, Rudolph S, Longo BN, et al (2022)

Bioengineered 3D tissue model of intestine epithelium with oxygen gradients to sustain human gut microbiome.

Advanced healthcare materials [Epub ahead of print].

The human gut microbiome is crucial to host physiology and health. Therefore, stable in vitro coculture of primary human intestinal cells with a microbiome community is essential for understanding intestinal disease progression and revealing novel therapeutic targets. Here, we present a three-dimensional (3D) scaffold system to regenerate an in vitro human intestinal epithelium that recapitulates many functional characteristics of the in vivo small intestine. The epithelium, derived from human intestinal enteroids, contains mature intestinal epithelial cell types and possesses selectively permeable barrier functions. Importantly, by properly positioning the scaffolds cultured under normal atmospheric conditions, two physiologically relevant oxygen gradients, a proximal-to-distal oxygen gradient along the gastrointestinal (GI) tract and a radial oxygen gradient across the epithelium, were distinguished in the tissues when the lumens were faced up and down in cultures, respectively. Furthermore, the presence of the low oxygen gradients supported the coculture of intestinal epithelial cells along with a complex living commensal gut microbiome (including obligate anaerobes) to simulate temporal microbiome dynamics in the native human gut. This unique silk scaffold platform may enable the exploration of microbiota-related mechanisms of disease pathogenesis and host-pathogen dynamics in infectious diseases including the potential to explore the human microbiome-gut-brain axis and potential novel microbiome-based therapeutics. This article is protected by copyright. All rights reserved.

RevDate: 2022-06-09

Wedenoja S, Saarikivi A, Mälkönen J, et al (2022)

Fecal microbiota in congenital chloride diarrhea and inflammatory bowel disease.

PloS one, 17(6):e0269561 pii:PONE-D-21-40434.

BACKGROUND AND AIMS: Subjects with congenital chloride diarrhea (CLD; a defect in solute carrier family 26 member 3 (SLC26A3)) are prone to inflammatory bowel disease (IBD). We investigated fecal microbiota in CLD and CLD-associated IBD. We also tested whether microbiota is modulated by supplementation with the short-chain fatty acid butyrate.

SUBJECTS AND METHODS: We recruited 30 patients with CLD for an observational 3-week follow-up study. Thereafter, 16 consented to oral butyrate substitution for a 3-week observational period. Fecal samples, collected once a week, were assayed for calprotectin and potential markers of inflammation, and studied by 16S ribosomal ribonucleic acid (rRNA) gene amplicon sequencing and compared to that of 19 healthy controls and 43 controls with Crohn's disease. Data on intestinal symptoms, diet and quality of life were collected.

RESULTS: Patients with CLD had increased abundances of Proteobacteria, Veillonella, and Prevotella, and lower abundances of normally dominant taxa Ruminococcaceae and Lachnospiraceae when compared with healthy controls and Crohn´s disease. No major differences in fecal microbiota were found between CLD and CLD-associated IBD (including two with yet untreated IBD). Butyrate was poorly tolerated and showed no major effects on fecal microbiota or biomarkers in CLD.

CONCLUSIONS: Fecal microbiota in CLD is different from that of healthy subjects or Crohn´s disease. Unexpectedly, no changes in the microbiota or fecal markers characterized CLD-associated IBD, an entity with high frequency among patients with CLD.

RevDate: 2022-06-09

Hou Y, Tan T, Guo Z, et al (2022)

Gram-selective antibacterial peptide hydrogels.

Biomaterials science [Epub ahead of print].

The human microbiome plays fundamental roles in human health and disease. However, widely used broad-spectrum antibiotics severely disrupt human-related microbial communities, eventually leading to resistant bacteria, posing a growing threat to global medical health. Antimicrobial peptides (AMPs) are promising antimicrobial agents that barely cause bacterial resistance. Excellent broad-spectrum antimicrobial activities have been achieved using hydrogels self-assembled from AMPs, but there is still a lack of AMP hydrogels that can target Gram-positive and Gram-negative bacteria. Herein, several hydrogels self-assembled from AMPs, termed IK1, IK3, and IK4, were designed and synthesized. In vitro antibacterial results indicated that the IK1 and IK4 hydrogels specifically targeted Gram-positive and Gram-negative bacteria, respectively, while the IK3 hydrogel targeted both Gram-positive and Gram-negative bacteria. The desired broad-spectrum or Gram-selective AMP hydrogels are believed to be obtained through the rational design of the hydrophilicity, hydrophobicity, and charge properties of the peptide molecules. Good in vivo Gram-selective antibacterial properties and the ability to promote wound healing have been demonstrated via treating mouse wound models with these AMP hydrogels. We believe that these Gram-selective AMP hydrogels could potentially have important applications in treating common recurring infections.

RevDate: 2022-06-09

Dedrick RM, Smith BE, Cristinziano M, et al (2022)

Phage Therapy of Mycobacterium Infections: Compassionate-use of Phages in Twenty Patients with Drug-Resistant Mycobacterial Disease.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America pii:6604409 [Epub ahead of print].

BACKGROUND: Non-tuberculous Mycobacterium (NTM) infections, particularly Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification.

METHODS: Mycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid.

RESULTS: No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favorable clinical or microbiological responses were observed in 11 patients. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in eight patients, potentially contributing to lack of treatment response in four cases but were not consistently associated with unfavorable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these.

CONCLUSIONS: Phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections.

RevDate: 2022-06-07

Shahzad M, Andrews SC, Z Ul-Haq (2022)

Exploring the role of Microbiome in Susceptibility, Treatment Response and Outcome among Tuberculosis Patients from Pakistan: study protocol for a prospective cohort study (Micro-STOP).

BMJ open, 12(6):e058463 pii:bmjopen-2021-058463.

INTRODUCTION: Tuberculosis (TB) caused by Mycobacterium tuberculosis is a common infectious disease associated with significant morbidity and mortality, especially in low-income and middle-income countries. Successful treatment of the disease requires prolonged intake (6-8 months) of multiple antibiotics with potentially detrimental consequences on the composition and functional potential of the human microbiome. The protocol described in the current study aims to identify microbiome (oral and gut) signatures associated with TB pathogenesis, treatment response and outcome in humans.

METHODS AND ANALYSIS: Four hundred and fifty, newly diagnosed patients with TB from three district levels (Peshawar, Mardan and Swat) TB diagnosis and treatment centres, will be recruited in this non-interventional, prospective cohort study and will be followed and monitored until treatment completion. Demographic and dietary intake data, anthropometric measurement and blood, stool and salivary rinse samples will be collected at baseline, day 15, month-2 and end of the treatment. Additionally, we will recruit age (±3 years) and sex-matched healthy controls (n=30). Blood sampling will allow monitoring of the immune response during the treatment, while salivary rinse and faecal samples will allow monitoring of dynamic changes in oral and gut microbiome diversity. Within this prospective cohort study, a nested case-control study design will be conducted to assess perturbations in oral and gut microbiome diversity (microbial dysbiosis) and immune response and compare between the patients groups (treatment success vs failure).

ETHICS AND DISSEMINATION: The study has received ethics approval from the Ethic Board of Khyber Medical University Peshawar, and administrative approval from Provincial TB Control Programme of Khyber Pakhtunkhwa, Pakistan. The study results will be presented in national and international conferences and published in peer-reviewed journals.


RevDate: 2022-06-06

Girgis HZ (2022)

MeShClust v3.0: high-quality clustering of DNA sequences using the mean shift algorithm and alignment-free identity scores.

BMC genomics, 23(1):423.

BACKGROUND: Tools for accurately clustering biological sequences are among the most important tools in computational biology. Two pioneering tools for clustering sequences are CD-HIT and UCLUST, both of which are fast and consume reasonable amounts of memory; however, there is a big room for improvement in terms of cluster quality. Motivated by this opportunity for improving cluster quality, we applied the mean shift algorithm in MeShClust v1.0. The mean shift algorithm is an instance of unsupervised learning. Its strong theoretical foundation guarantees the convergence to the true cluster centers. Our implementation of the mean shift algorithm in MeShClust v1.0 was a step forward. In this work, we scale up the algorithm by adapting an out-of-core strategy while utilizing alignment-free identity scores in a new tool: MeShClust v3.0.

RESULTS: We evaluated CD-HIT, MeShClust v1.0, MeShClust v3.0, and UCLUST on 22 synthetic sets and five real sets. These data sets were designed or selected for testing the tools in terms of scalability and different similarity levels among sequences comprising clusters. On the synthetic data sets, MeShClust v3.0 outperformed the related tools on all sets in terms of cluster quality. On two real data sets obtained from human microbiome and maize transposons, MeShClust v3.0 outperformed the related tools by wide margins, achieving 55%-300% improvement in cluster quality. On another set that includes degenerate viral sequences, MeShClust v3.0 came third. On two bacterial sets, MeShClust v3.0 was the only applicable tool because of the long sequences in these sets. MeShClust v3.0 requires more time and memory than the related tools; almost all personal computers at the time of this writing can accommodate such requirements. MeShClust v3.0 can estimate an important parameter that controls cluster membership with high accuracy.

CONCLUSIONS: These results demonstrate the high quality of clusters produced by MeShClust v3.0 and its ability to apply the mean shift algorithm to large data sets and long sequences. Because clustering tools are utilized in many studies, providing high-quality clusters will help with deriving accurate biological knowledge.

RevDate: 2022-06-06

Chueachavalit C, Meephansan J, Payungporn S, et al (2022)

Comparison of Malassezia spp. colonization between human skin exposed to high and low ambient air pollution.

Experimental dermatology [Epub ahead of print].

BACKGROUND: The skin microbiota is essential for human health; altered skin microbiome colonization and homeostasis may be associated with several inflammatory skin conditions and other inflammatory diseases. The effects of particulate matter of diameter less than 2.5 micrometers (PM2.5) on the skin and the skin microbiome are poorly understood. Malassezia spp. are commensal fungi commonly found on the human skin, and they also play a pathogenic role in various skin diseases. It is hypothesized that the exposure of human skin to air pollution with a high concentration of PM2.5 might be associated with Malassezia spp. colonization. The aim of this study was to compare Malassezia spp. colonization on healthy human skin between people living in two major cities in Thailand with different air qualities: one city with highly polluted ambient air and the other with less polluted air.

METHODS: Skin microbiome samples from 66 participants were collected using swabbing and scraping techniques. The skin fungal composition was analyzed using high-throughput sequencing based on internal transcribed spacer 2 (ITS2) rDNA.

RESULTS: A significant difference was found in alpha and beta diversities and the relative abundance of fungal profiles between the groups. The relative abundance of Malassezia spp. was found to be significantly higher in the highly polluted area than in the less polluted area.

CONCLUSION: This study demonstrates that ambient air polluted with high concentrations of PM2.5 may alter Malassezia spp. colonization on healthy human skin, which could lead to dysbiosis of the cutaneous ecosystem and eventually result in some skin disorders.

RevDate: 2022-06-06

Chen Q, Lin S, C Song (2022)

An Adaptive and Robust Test for Microbial Community Analysis.

Frontiers in genetics, 13:846258 pii:846258.

In microbiome studies, researchers measure the abundance of each operational taxon unit (OTU) and are often interested in testing the association between the microbiota and the clinical outcome while conditional on certain covariates. Two types of approaches exists for this testing purpose: the OTU-level tests that assess the association between each OTU and the outcome, and the community-level tests that examine the microbial community all together. It is of considerable interest to develop methods that enjoy both the flexibility of OTU-level tests and the biological relevance of community-level tests. We proposed MiAF, a method that adaptively combines p-values from the OTU-level tests to construct a community-level test. By borrowing the flexibility of OTU-level tests, the proposed method has great potential to generate a series of community-level tests that suit a range of different microbiome profiles, while achieving the desirable high statistical power of community-level testing methods. Using simulation study and real data applications in a smoker throat microbiome study and a HIV patient stool microbiome study, we demonstrated that MiAF has comparable or better power than methods that are specifically designed for community-level tests. The proposed method also provides a natural heuristic taxa selection.

RevDate: 2022-06-06

Wang L, Zhang W, Wu X, et al (2022)

MIAOME: Human microbiome affect the host epigenome.

Computational and structural biotechnology journal, 20:2455-2463 pii:S2001-0370(22)00180-5.

Besides the genetic factors having tremendous influences on the regulations of the epigenome, the microenvironmental factors have recently gained extensive attention for their roles in affecting the host epigenome. There are three major types of microenvironmental factors: microbiota-derived metabolites (MDM), microbiota-derived components (MDC) and microbiota-secreted proteins (MSP). These factors can regulate host physiology by modifying host gene expression through the three highly interconnected epigenetic mechanisms (e.g. histone modifications, DNA modifications, and non-coding RNAs). However, no database was available to provide the comprehensive factors of these types. Herein, a database entitled 'Human Microbiome Affect The Host Epigenome (MIAOME)' was constructed. Based on the types of epigenetic modifications confirmed in the literature review, the MIAOME database captures 1068 (63 genus, 281 species, 707 strains, etc.) human microbes, 91 unique microbiota-derived metabolites & components (16 fatty acids, 10 bile acids, 10 phenolic compounds, 10 vitamins, 9 tryptophan metabolites, etc.) derived from 967 microbes; 50 microbes that secreted 40 proteins; 98 microbes that directly influence the host epigenetic modification, and provides 3 classifications of the epigenome, including (1) 4 types of DNA modifications, (2) 20 histone modifications and (3) 490 ncRNAs regulations, involved in 160 human diseases. All in all, MIAOME has compiled the information on the microenvironmental factors influence host epigenome through the scientific literature and biochemical databases, and allows the collective considerations among the different types of factors. It can be freely assessed without login requirement by all users at:

RevDate: 2022-06-07

Cohen LJ, Han SM, Lau P, et al (2022)

Unraveling function and diversity of bacterial lectins in the human microbiome.

Nature communications, 13(1):3101.

The mechanisms by which commensal organisms affect human physiology remain poorly understood. Lectins are non-enzymatic carbohydrate binding proteins that all organisms employ as part of establishing a niche, evading host-defenses and protecting against pathogens. Although lectins have been extensively studied in plants, bacterial pathogens and human immune cells for their role in disease pathophysiology and as therapeutics, the role of bacterial lectins in the human microbiome is largely unexplored. Here we report on the characterization of a lectin produced by a common human associated bacterium that interacts with myeloid cells in the blood and intestine. In mouse and cell-based models, we demonstrate that this lectin induces distinct immunologic responses in peripheral and intestinal leukocytes and that these responses are specific to monocytes, macrophages and dendritic cells. Our analysis of human microbiota sequencing data reveal thousands of unique sequences that are predicted to encode lectins, many of which are highly prevalent in the human microbiome yet completely uncharacterized. Based on the varied domain architectures of these lectins we predict they will have diverse effects on the human host. The systematic investigation of lectins in the human microbiome should improve our understanding of human health and provide new therapeutic opportunities.

RevDate: 2022-06-07

Almand AT, Anderson AP, Hitt BD, et al (2022)

The influence of perceived stress on the human microbiome.

BMC research notes, 15(1):193.

OBJECTIVE: Microbial dysbiosis, a shift from commensal to pathogenic microbiota, is often associated with mental health and the gut-brain axis, where dysbiosis in the gut may be linked to dysfunction in the brain. Many studies focus on dysbiosis induced by clinical events or traumatic incidents; however, many professions in austere or demanding environments may encounter continuously compounded stressors. This study seeks to explore the relationship between microbial populations and stress, both perceived and biochemical.

RESULTS: Eight individuals enrolled in the study to provide a longitudinal assessment of the impact of stress on gut health, with four individuals providing enough samples for analysis. Eleven core microbial genera were identified, although the relative abundance of these genera and other members of the microbial population shifted over time. Although our results indicate a potential relationship between perceived stress and microbial composition of the gut, no association with biochemical stress was observed. Increases in perceived stress seem to elucidate a change in potentially beneficial Bacteroides, with a loss in Firmicutes phyla. This shift occurred in multiple individuals, whereas using cortisol as a stress biomarker showed contradictory responses. These preliminary data provide a potential mechanism for gut monitoring, while identifying targets for downstream modulation.

RevDate: 2022-06-06

Naud S, Ibrahim A, Valles C, et al (2022)

Candidate Phyla Radiation, an Underappreciated Division of the Human Microbiome, and Its Impact on Health and Disease.

Clinical microbiology reviews [Epub ahead of print].

Candidate phyla radiation (CPR) is an emerging division of the bacterial domain within the human microbiota. Still poorly known, these microorganisms were first described in the environment in 1981 as "ultramicrobacteria" with a cell volume under 0.1 μm3 and were first associated with the human oral microbiota in 2007. The evolution of technology has been paramount for the study of CPR within the human microbiota. In fact, since these ultramicrobacteria have yet to be axenically cultured despite ongoing efforts, progress in imaging technology has allowed their observation and morphological description. Although their genomic abilities and taxonomy are still being studied, great strides have been made regarding their taxonomic classification, as well as their lifestyle. In addition, advancements in next-generation sequencing and the continued development of bioinformatics tools have allowed their detection as commensals in different human habitats, including the oral cavity and gastrointestinal and genital tracts, thus highlighting CPR as a nonnegligible part of the human microbiota with an impact on physiological settings. Conversely, several pathologies present dysbiosis affecting CPR levels, including inflammatory, mucosal, and infectious diseases. In this exhaustive review of the literature, we provide a historical perspective on the study of CPR, an overview of the methods available to study these organisms and a description of their taxonomy and lifestyle. In addition, their distribution in the human microbiome is presented in both homeostatic and dysbiotic settings. Future efforts should focus on developing cocultures and, if possible, axenic cultures to obtain isolates and therefore genomes that would provide a better understanding of these ultramicrobacteria, the importance of which in the human microbiome is undeniable.

RevDate: 2022-06-06
CmpDate: 2022-06-06

Stockdale SR, Harrington RS, Shkoporov AN, et al (2022)

Metagenomic assembled plasmids of the human microbiome vary across disease cohorts.

Scientific reports, 12(1):9212.

We compiled a human metagenome assembled plasmid (MAP) database and interrogated differences across multiple studies that were originally designed to investigate the composition of the human microbiome across various lifestyles, life stages and events. This was performed as plasmids enable bacteria to rapidly expand their functional capacity through mobilisation, yet their contribution to human health and disease is poorly understood. We observed that inter-sample β-diversity differences of plasmid content (plasmidome) could distinguish cohorts across a multitude of conditions. We also show that reduced intra-sample plasmidome α-diversity is consistent amongst patients with inflammatory bowel disease (IBD) and Clostridioides difficile infections. We also show that faecal microbiota transplants can restore plasmidome diversity. Overall plasmidome diversity, specific plasmids, and plasmid-encoded functions can all potentially act as biomarkers of IBD or its severity. The human plasmidome is an overlooked facet of the microbiome and should be integrated into investigations regarding the role of the microbiome in promoting health or disease. Including MAP databases in analyses will enable a greater understanding of the roles of plasmid-encoded functions within the gut microbiome and will inform future human metagenome analyses.

RevDate: 2022-06-02

Bhoite SS, Han Y, Ruotolo BT, et al (2022)

Mechanistic insights into accelerated α-synuclein aggregation mediated by human microbiome-associated functional amyloids.

The Journal of biological chemistry pii:S0021-9258(22)00529-4 [Epub ahead of print].

The gut microbiome has been shown to have key implications in the pathogenesis of Parkinson's disease (PD). The E. coli functional amyloid CsgA is known to accelerate α-synuclein aggregation in vitro and induce PD symptoms in mice. However, the mechanism governing CsgA-mediated acceleration of α-synuclein aggregation is unclear. Here, we show that CsgA can form stable homodimeric species that correlate with faster α-synuclein amyloid aggregation. Furthermore, we identify and characterize new CsgA homologs encoded by bacteria present in the human microbiome. These CsgA homologs display diverse aggregation kinetics, and they differ in their ability to modulate α-synuclein aggregation. Remarkably, we demonstrate that slowing down CsgA aggregation leads to increased acceleration of α-synuclein aggregation suggesting that the intrinsic amyloidogenicity of gut bacterial CsgA homologs affects their ability to accelerate α-synuclein aggregation. Finally, we identify a complex between CsgA and α-synuclein that functions as a platform to accelerate α-synuclein aggregation. Taken together, our work reveals complex interplay between bacterial amyloids and α-synuclein that better informs our understanding of PD causation.

RevDate: 2022-06-01

Pausan MR, Blohs M, Mahnert A, et al (2022)

The sanitary indoor environment-a potential source for intact human-associated anaerobes.

NPJ biofilms and microbiomes, 8(1):44.

A healthy human microbiome relies on the interaction with and exchange of microbes that takes place between the human body and its environment. People in high-income countries spend most of their time indoors and for this reason, the built environment (BE) might represent a potent source of commensal microbes. Anaerobic microbes are of particular interest, as researchers have not yet sufficiently clarified how the human microbiome acquires oxygen-sensitive microbes. We sampled the bathrooms in ten households and used propidium monoazide (PMA) to assess the viability of the collected prokaryotes. We compared the microbiome profiles based on 16S rRNA gene sequencing and confirmed our results by genetic and cultivation-based analyses. Quantitative and qualitative analysis revealed that most of the microbial taxa in the BE samples are human-associated. Less than 25% of the prokaryotic signatures originate from intact cells, indicating that aerobic and stress resistant taxa display an apparent survival advantage. However, we also confirmed the presence of intact, strictly anaerobic taxa on bathroom floors, including methanogenic archaea. As methanogens are regarded as highly sensitive to aerobic conditions, oxygen-tolerance experiments were performed with human-associated isolates to validate their survival. These results show that human-associated methanogens can survive oxic conditions for at least 6 h. We collected strong evidence that supports the hypothesis that obligate anaerobic taxa can survive in the BE for a limited amount of time. This suggests that the BE serves as a potential source of anaerobic human commensals.

RevDate: 2022-06-01

Guthrie L, Spencer SP, Perelman D, et al (2022)

Impact of a 7-day homogeneous diet on interpersonal variation in human gut microbiomes and metabolomes.

Cell host & microbe pii:S1931-3128(22)00263-3 [Epub ahead of print].

Gut microbiota metabolism of dietary compounds generates a vast array of microbiome-dependent metabolites (MDMs), which are highly variable between individuals. The uremic MDMs (uMDMs) phenylacetylglutamine (PAG), p-cresol sulfate (PCS), and indoxyl sulfate (IS) accumulate during renal failure and are associated with poor outcomes. Targeted dietary interventions may reduce toxic MDM generation; however, it is unclear if inter-individual differences in diet or gut microbiome dominantly contribute to MDM variance. Here, we use a 7-day homogeneous average American diet to standardize dietary precursor availability in 21 healthy individuals. During dietary homogeneity, the coefficient of variation in PAG, PCS, and IS (primary outcome) did not decrease, nor did inter-individual variation in most identified metabolites; other microbiome metrics showed no or modest responses to the intervention. Host identity and age are dominant contributors to variability in MDMs. These results highlight the potential need to pair dietary modification with microbial therapies to control MDM profiles.

RevDate: 2022-05-31

Attai H, Wilde J, Liu R, et al (2022)

Bacteriophage-Mediated Perturbation of Defined Bacterial Communities in an In Vitro Model of the Human Gut.

Microbiology spectrum [Epub ahead of print].

The study of bacteriophage communities reproducing in the gastrointestinal tract is limited by the quality of model systems supporting experimental manipulation in vitro. Traditionally, studies aiming to experimentally address phage-bacteria dynamics have utilized gnotobiotic mice inoculated with defined bacterial communities. While mouse models simulate complex interactions between microbes and their host, they also forestall the study of phage-bacteria dynamics in isolation of host factors. Here, we established a method for manipulating phage-bacteria dynamics using an in vitro chemostat bioreactor model of the distal human gut. We create defined communities representing a subset of bacteria in the feces of two human individuals, cultivated these communities in chemostat bioreactors, developed methods to purify the autochthonous viromes associated with each cultured community, and trialed a system for transmitting live or heat-killed viruses between chemostat bioreactors to decipher outcomes of virus-mediated perturbation. We found that allochthonous viromes were detectable via metagenomic sequencing against the autochthonous virome background and that shifts in bacterial community diversity and composition were detectable in relation to time posttreatment. These microbiome composition changes spanned multiple phyla, including Bacteroidetes, Firmicutes, and Actinobacteria. We also found that compositional changes occurred when using live viruses regardless of whether intrasubject or intersubject viruses were used as the perturbation agents. Our results supported the use of chemostat bioreactors as a platform for studying complex bacteria-phage dynamics in vitro. IMPORTANCE Bacteriophages are relatively ubiquitous in the environment and are highly abundant in the human microbiome. Phages can be commonly transmitted between close contacts, but the impact that such transmissions may have on their bacteria counterparts in our microbiomes is unknown. We developed a chemostat cultivation system to simulate individual-specific features of human distal gut microbiota that can be used to transmit phages between ecosystems and measure their impacts on the microbiota. We used this system to transfer phage communities between chemostats that represented different human subjects. We found that there were significant effects on overall microbiota diversity and changes in the relative abundances of Bacteroidetes, Firmicutes, and Actinobacteria, when intersubject perturbations were performed, compared to intrasubject perturbations. These changes were observed when perturbations were performed using live phages, but not when heat-killed phages were used, and they support the use of chemostat systems for studying complex human bacteria-phage dynamics.

RevDate: 2022-05-31

Bryan NS, Burleigh MC, C Easton (2022)

The oral microbiome, nitric oxide and exercise performance.

Nitric oxide : biology and chemistry pii:S1089-8603(22)00054-4 [Epub ahead of print].

The human microbiome comprises ∼1013-1014 microbial cells which form a symbiotic relationship with the host and play a critical role in the regulation of human metabolism. In the oral cavity, several species of bacteria are capable of reducing nitrate to nitrite; a key precursor of the signaling molecule nitric oxide. Nitric oxide has myriad physiological functions, which include the maintenance of cardiovascular homeostasis and the regulation of acute and chronic responses to exercise. This article provides a brief narrative review of the research that has explored how diversity and plasticity of the oral microbiome influences nitric oxide bioavailability and related physiological outcomes. There is unequivocal evidence that dysbiosis (e.g. through disease) or disruption (e.g. by use of antiseptic mouthwash or antibiotics) of the oral microbiota will suppress nitric oxide production via the nitrate-nitrite-nitric oxide pathway and negatively impact blood pressure. Conversely, there is preliminary evidence to suggest that proliferation of nitrate-reducing bacteria via the diet or targeted probiotics can augment nitric oxide production and improve markers of oral health. Despite this, it is yet to be established whether purposefully altering the oral microbiome can have a meaningful impact on exercise performance. Future research should determine whether alterations to the composition and metabolic activity of bacteria in the mouth influence the acute responses to exercise and the physiological adaptations to exercise training.

RevDate: 2022-05-31

Maestre-Carballa L, Navarro-López V, M Martinez-Garcia (2022)

A Resistome Roadmap: From the Human Body to Pristine Environments.

Frontiers in microbiology, 13:858831.

A comprehensive characterization of the human body resistome [sets of antibiotic resistance genes (ARGs)] is yet to be done and paramount for addressing the antibiotic microbial resistance threat. Here, we study the resistome of 771 samples from five major body parts (skin, nares, vagina, gut, and oral cavity) of healthy subjects from the Human Microbiome Project (HMP) and addressed the potential dispersion of ARGs in pristine environments. A total of 28,714 ARGs belonging to 235 different ARG types were found in the HMP proteome dataset (n = 9.1 × 107 proteins analyzed). Our study reveals a distinct resistome profile (ARG type and abundance) between body sites and high interindividual variability. Nares had the highest ARG load (≈5.4 genes/genome) followed by the oral cavity, whereas the gut showed one of the highest ARG richness (shared with nares) but the lowest abundance (≈1.3 genes/genome). The fluroquinolone resistance genes were the most abundant in the human body, followed by macrolide-lincosamide-streptogramin (MLS) or tetracycline. Most ARGs belonged to common bacterial commensals and multidrug resistance trait were predominant in the nares and vagina. Many ARGs detected here were considered as low risk for human health, whereas only a few of them, such as BlaZ, dfrA14, dfrA17, or tetM, were classified as high-risk ARG. Our data also provide hope, since the spread of common ARG from the human body to pristine environments (n = 271 samples; 77 Gb of sequencing data and 2.1 × 108 proteins analyzed) thus far remains very unlikely (only one case found in an autochthonous bacterium from a pristine environment). These findings broaden our understanding of ARG in the context of the human microbiome and the One-Health Initiative of WHO uniting human host-microbes and environments as a whole.

RevDate: 2022-05-31

El-Chami C, Choudhury R, Mohammedsaeed W, et al (2022)

Multiple Proteins of Lacticaseibacillus rhamnosus GG Are Involved in the Protection of Keratinocytes From the Toxic Effects of Staphylococcus aureus.

Frontiers in microbiology, 13:875542.

We have previously shown that lysates of Lacticaseibacillus rhamnosus GG confer protection to human keratinocytes against Staphylococcus aureus. L. rhamnosus GG inhibits the growth of S. aureus as well as competitively excludes and displaces the pathogen from keratinocytes. In this study, we have specifically investigated the anti-adhesive action. We have tested the hypothesis that this activity is due to quenching of S. aureus binding sites on keratinocytes by molecules within the Lacticaseibacillus lysate. Trypsinisation or heat treatment removed the protective effect of the lysate suggesting the involvement of proteins as effector molecules. Column separation of the lysate and analysis of discrete fractions in adhesion assays identified a fraction of moderate hydrophobicity that possessed all anti-adhesive functions. Immunoblotting demonstrated that this fraction contained the pilus protein, SpaC. Recombinant SpaC inhibited staphylococcal adhesion to keratinocytes in a dose-dependent manner and improved keratinocyte viability following challenge with viable S. aureus. However, SpaC did not confer the full anti-adhesive effects of the LGG lysate and excluded but did not displace S. aureus from keratinocytes. Further purification produced four protein-containing peaks (F1-F4). Of these, F4, which had the greatest column retention time, was the most efficacious in anti-staphylococcal adhesion and keratinocyte viability assays. Identification of proteins by mass spectrometry showed F4 to contain several known "moonlighting proteins"-i.e., with additional activities to the canonical function, including enolase, Triosephosphate isomerase (TPI), Glyceraldehyde 3 phosphate dehydrogenase (G3P) and Elongation factor TU (EF-Tu). Of these, only enolase and TPI inhibited S. aureus adhesion and protected keratinocytes viability in a dose-dependent manner. These data suggest that inhibition of staphylococcal binding by the L. rhamnosus GG lysate is mediated by SpaC and specific moonlight proteins.

RevDate: 2022-05-28

Brogna C, Brogna B, Bisaccia DR, et al (2022)

Could SARS-CoV-2 Have Bacteriophage Behavior or Induce the Activity of Other Bacteriophages?.

Vaccines, 10(5): pii:vaccines10050708.

SARS-CoV-2 has become one of the most studied viruses of the last century. It was assumed that the only possible host for these types of viruses was mammalian eukaryotic cells. Our recent studies show that microorganisms in the human gastrointestinal tract affect the severity of COVID-19 and for the first time provide indications that the virus might replicate in gut bacteria. In order to further support these findings, in the present work, cultures of bacteria from the human microbiome and SARS-CoV-2 were analyzed by electron and fluorescence microscopy. The images presented in this article, in association with the nitrogen (15N) isotope-labeled culture medium experiment, suggest that SARS-CoV-2 could also infect bacteria in the gut microbiota, indicating that SARS-CoV-2 could act as a bacteriophage. Our results add new knowledge to the understanding of the mechanisms of SARS-CoV-2 infection and fill gaps in the study of the interactions between SARS-CoV-2 and non-mammalian cells. These findings could be useful in suggesting specific new pharmacological solutions to support the vaccination campaign.

RevDate: 2022-05-28

Harutyunyan N, Kushugulova A, Hovhannisyan N, et al (2022)

One Health Probiotics as Biocontrol Agents: One Health Tomato Probiotics.

Plants (Basel, Switzerland), 11(10): pii:plants11101334.

Tomato (Lycopersicon esculentum) is one of the most popular and valuable vegetables in the world. The most common products of its industrial processing in the food industry are juice, tomato paste, various sauces, canned or sun-dried fruits and powdered products. Tomato fruits are susceptible to bacterial diseases, and bacterial contamination can be a risk factor for the safety of processed tomato products. Developments in bioinformatics allow researchers to discuss target probiotic strains from an existing large number of probiotic strains for any link in the soil-plant-animal-human chain. Based on the literature and knowledge on the "One Health" concept, this study relates to the suggestion of a new term for probiotics: "One Health probiotics", beneficial for the unity of people, animals, and the environment. Strains of Lactiplantibacillus plantarum, having an ability to ferment a broad spectrum of plant carbohydrates, probiotic effects in human, and animal health, as well as being found in dairy products, vegetables, sauerkraut, pickles, some cheeses, fermented sausages, fish products, and rhizospheric soil, might be suggested as one of the probable candidates for "One Health" probiotics (also, for "One Health-tomato" probiotics) for the utilization in agriculture, food processing, and healthcare.

RevDate: 2022-05-28

Pane S, L Putignani (2022)

Cryptosporidium: Still Open Scenarios.

Pathogens (Basel, Switzerland), 11(5): pii:pathogens11050515.

Cryptosporidiosis is increasingly identified as a leading cause of childhood diarrhea and malnutrition in both low-income and high-income countries. The strong impact on public health in epidemic scenarios makes it increasingly essential to identify the sources of infection and understand the transmission routes in order to apply the right prevention or treatment protocols. The objective of this literature review was to present an overview of the current state of human cryptosporidiosis, reviewing risk factors, discussing advances in the drug treatment and epidemiology, and emphasizing the need to identify a government system for reporting diagnosed cases, hitherto undervalued.

RevDate: 2022-05-28

Puigbò P, Leino LI, Rainio MJ, et al (2022)

Does Glyphosate Affect the Human Microbiota?.

Life (Basel, Switzerland), 12(5): pii:life12050707.

Glyphosate is the world's most widely used agrochemical. Its use in agriculture and gardening has been proclaimed safe because humans and other animals do not have the target enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). However, increasing numbers of studies have demonstrated risks to humans and animals because the shikimate metabolic pathway is present in many microbes. Here, we assess the potential effect of glyphosate on healthy human microbiota. Our results demonstrate that more than one-half of human microbiome are intrinsically sensitive to glyphosate. However, further empirical studies are needed to determine the effect of glyphosate on healthy human microbiota.


ESP Quick Facts

ESP Origins

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.

ESP Support

In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

ESP Rationale

Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

ESP Goal

In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.

ESP Usage

Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

ESP Content

When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

ESP Help

Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

ESP Plans

With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

Electronic Scholarly Publishing
961 Red Tail Lane
Bellingham, WA 98226

E-mail: RJR8222 @

Papers in Classical Genetics

The ESP began as an effort to share a handful of key papers from the early days of classical genetics. Now the collection has grown to include hundreds of papers, in full-text format.

Digital Books

Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin (and even a collection of poetry — Chicago Poems by Carl Sandburg).


ESP now offers a much improved and expanded collection of timelines, designed to give the user choice over subject matter and dates.


Biographical information about many key scientists.

Selected Bibliographies

Bibliographies on several topics of potential interest to the ESP community are now being automatically maintained and generated on the ESP site.

ESP Picks from Around the Web (updated 07 JUL 2018 )