Female genital tract (FGT) diseases such as bacterial vaginosis (BV) and sexually transmitted infections are prevalent in South Africa, with young women being at an increased risk. Since imbalances in the FGT microbiome are associated with FGT diseases, it is vital to investigate the factors that influence FGT health. The mycobiome plays an important role in regulating mucosal health, especially when the bacterial component is disturbed. However, we have a limited understanding of the FGT mycobiome since many studies have focused on bacterial communities and have neglected low-abundance taxonomic groups, such as fungi. To reduce this knowledge deficit, we present the first large-scale metaproteomic study to define the taxonomic composition and potential functional processes of the FGT mycobiome in South African reproductive-age women. We examined FGT fungal communities present in 123 women by collecting lateral vaginal wall swabs for liquid chromatography-tandem mass spectrometry. From this, 39 different fungal genera were identified, with Candida dominating the mycobiome (53.2
The relationship between gut microbiota and obesity has been investigated in numerous studies. However, inter-individual heterogeneity influenced by multiple factors may explain the inconsistent findings in human studies. Our primary aim was to identify the specific gut microbial composition that distinguishes obese male and female children from normal-weight children based on their body mass index (BMI) and to compare the results with previous analyses. Methods: Gut microbiome 16S rRNA sequences data from participants divided into three groups based on age (6–16 years), gender, and weight status: 13 obese female and 6 normal-weight female children, 13 obese male and 5 normal-weight male children, and a combined group of 13 obese male and 13 obese female children, has been analyzed using he EZBiocloud public data and analytics portal. Results: Gut microbiome composition of obese female and male children groups showed significant differences in terms of their alpha and beta diversity indices. Obese female children had significantly higher alpha diversity indices than male children with obesity. The increase in alpha diversity indices observed among female children with obesity indicates higher microbial diversity within their gut microbiota. Moreover, the analysis of beta diversity uncovered notable distinctions in the gut microbiota composition among subgroups of obese male and female children. We propose that bacterial microbiota, such as Bifidobacterium lactis and Lactobacillus rhamnosus, could potentially function as health indicators in obese children of both sexes. These microbial genera might be useful in aiding obese children to manage weight problems and alleviating metabolic disorders associated with obesity. Conclusions: Gender plays a crucial role in the composition of the gut microbiota of obese children. This finding emphasizes the necessity of considering gender-specific factors in both obesity research and management. Furthermore, using prebiotic and probiotic supplements in childhood obesity treatments could act as useful adjuncts to regulate gut microbiota composition and improve metabolic health. This approach aims to modify relative microbial abundance.
Background: Necrotizing enterocolitis (NEC) is a devastating intestinal disease that affects preterm infants and remains a leading cause of morbidity and mortality in this population. The gut microbiome has been implicated in the pathogenesis of NEC, and the taxonomic composition can vary depending on several factors, including geography. This study aims to compare the gut microbiome composition and abundance in preterm infants with NEC from the United States and Brazil to explore the impact of geography and ethnicity. Methods: This cohort study included forty-three (43) fecal samples from twenty- one (21) preterm infants with NEC from the United States USA and Brazil. A 16S rRNA amplicon profiling approach was conducted on extracted fecal DNA to characterize the gut microbiome composition and abundance of those NEC infants. The inclusion criteria were preterm infants with a confirmed diagnosis of NEC, birth weight between 440 g and 2101 g, gestational age under 34 weeks, and neonatal antibiotic exposure. The exclusion criteria were children with complex congenital cardiopathy or spontaneous intestinal perforation without radiological evidence of NEC. Taxonomic and statistical analyses were conducted via the EzBioCloud platform to identify the differences in gut microbiome composition and abundance between the infants from these 2 countries. Results: Differences in gut microbiome composition and abundance between NEC-preterm infants in the United States and Brazil has been demonstrated. The USA group had a higher abundance of Pseudomonadota and a lower abundance of Actinobacteria and Bacteroidetes, while the Brazil group had a higher abundance of Firmicutes and a lower abundance of Proteobacteria. At the genus level, Staphylococcus was most predominant in the USA group, while Bacteroides and Prevotella were most predominant in Brazil. Conclusion: The study findings revealed significant compositional and abundance differences in the gut microbiome of NEC-preterm infants between the USA and Brazil, suggesting geographical and ethnicity variations impact on the gut microbiome of NEC infants. This study will help improve our understanding of NEC pathogenesis and the development of targeted interventions, taking in consideration the geographical and ethnic specificities of the subjects.
Background: While a substantial body of research has been dedicated to exploring the influence of alterations in the brain-gut-microbiome axis on conditions like depression and other mental disorders, there has been comparatively less focus on understanding how the oral microbiome affects brain function, particularly in response to smoking. Depression has been found to have a potential connection with oral dysbiosis, a condition that has shown associations with various disorders. Methods: We conducted an analysis of the oral saliva microbiome data (accession number: PRJEB44565) from a cohort of 44 adult participants to explore the link between oral microbiome composition and depression, with a particular focus on distinguishing between smokers and nonsmokers. Our study involved a comparison of salivary microbiome data between individuals with depression (n = 22) and a matched control group (n = 22). Within the depressed cohort, we further stratified participants into two subgroups: smokers (n = 11) and nonsmokers (n = 11). To analyze the microbiome data, we employed the SRA Toolkit for gut microbiome data retrieval and conducted taxonomic classification and diversity assessments using the EZBioCloud server. Results: We observed significant disparities in both the abundance and diversity of the oral microbiome when comparing smokers to nonsmokers. In the salivary microbiome of smokers who were part of the depressed cohort, the predominant phyla were Bacteroidetes (37.91
The vaginal microbiome is designed to have low bacterial diversity and is dominated by Lactobacillus species, which acidify this environment and protect against invading pathogens. However, dysbiosis of the vaginal microbiome contributes to many pathologies, including bacterial vaginosis (BV). In microbiome research, NGS technologies are used to analyze the 16S rRNA gene, a molecular marker present in all bacteria and archaea. This gene variability allows researchers to identify different microbial species, providing insights into community composition and diversity. We explored the vaginal microbiome composition in thirty-three North African women using 16S rRNA V3–V4 region sequencing. The number of samples was 11 diseased non-pregnant (DNP), 7 diseased pregnant (DP), 9 healthy non-pregnant (HNP), and 6 healthy pregnant (HP) women at reproductive age (25–40 years old). We intended to identify bacterial taxonomy and diversity using two bioinformatics tools, the DADA2 and EzBioCloud 16S-based Microbiome Taxonomic Profiling (MTP) pipelines. Our findings revealed an overrepresentation of pathogenic bacteria at the species level within women with BV, identified using the EzBioCloud MTP pipeline. Consequently, our efforts resulted in the effective elucidation of bacterial species and diversity using the EzBioCloud 16S-based MTP pipeline. This result contrasts with our efforts using DADA2, where the objective of species differentiation remained unachievable. EzBioCloud makes it a feasible choice for incorporation into clinical diagnostic protocols and novel therapy techniques for bacterial vaginosis. Its ability to distinguish microbiome taxonomy and identify constituent species has the potential to improve our understanding of this disorder and potentially guide therapeutic interventions.
There is growing evidence that comprehensive and harmonized metadata are fundamental for effective public data reusability. However, it is often challenging to extract accurate metadata from public repositories. Of particular concern is the metagenomic data related to African individuals, which often omit important information about the particular features of these populations. As part of a collaborative consortium, H3ABioNet, we created a web portal, namely the African Human Microbiome Portal (AHMP), exclusively dedicated to metadata related to African human microbiome samples. Metadata were collected from various public repositories prior to cleaning, curation and harmonization according to a pre-established guideline and using ontology terms. These metadata sets can be accessed at https://microbiome.h3abionet.org/. This web portal is open access and offers an interactive visualization of 14 889 records from 70 bioprojects associated with 72 peer reviewed research articles. It also offers the ability to download harmonized metadata according to the user's applied filters. The AHMP thereby supports metadata search and retrieve operations, facilitating, thus, access to relevant studies linked to the African Human microbiome.Database URL: https://microbiome.h3abionet.org/.
Microbiome research has made significant gains with the evolution of sequencing technologies. Ensuring comparability between studies and enhancing the findability, accessibility, interoperability and reproducibility of microbiome data are crucial for maximizing the value of this growing body of research. Addressing the challenges of standardized metadata reporting, collection and curation, the Microbiome Working Group of the Human Hereditary and Health in Africa (H3Africa) consortium aimed to develop a comprehensive solution. In this paper, we present the Microbiome Research Data Toolkit, a versatile tool designed to standardize microbiome research metadata, facilitate MIxS-MIMS and PhenX reporting, standardize prospective collection of participant biological and lifestyle data, and retrospectively harmonize such data. This toolkit enables past, present and future microbiome research endeavors to collaborate effectively, fostering novel collaborations and accelerating knowledge discovery in the field. Database URL: https://doi.org/10.25375/uct.24218999.v2.
COVID-19 is a disease caused by SARS-CoV-2. The entry of a virus into human cells is a critical phase in its infection. The binding of the spike protein of SARS-CoV-2 to Angiotensin converting enzyme 2 ACE2, an enzyme found on the surface of human cells, initiates the infection. Online software tools that overlay the three-dimensional structures of viruses, including SARS-CoV-2, address the problem of structure superposition by overlaying the ACE2 and spike complexes of the first protein on those of the second protein. In this work, overlaying the three-dimensional structures of viruses was addressed by superimposing ACE2 and then applying the resulting transformation from this superposition to the spike. Finally, the root mean square deviation RMSD was calculated. We used the discrete to continuous DTC algorithm to align the 3D structures; the results from the DTC were compared to the results from TopMatch and SuperPose, which are online tools for aligning 3D structures. The obtained results prove that aligning each structure then combining them is the most suitable approach for properly studying the structural evolution of SARS-CoV-2.
We explored the gut microbiome composition in four Moroccan patients with coronavirus disease 2019 (COVID-19) during hospitalization and treatment, using 16S rRNA gene amplicon metataxonomic profiling, and compared it with that in four healthy severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-free control subjects.
The emergence of a novel coronavirus that later on rendered a global pandemic, caused desperation within the communities and drove increased interest in exploring medicinal plant–based therapeutics to treat and prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infections. Many medicinal plants have been reported to have antiviral, anti-inflammatory, and immunomodulatory effects that hinder, cure, or ease the symptoms of COVID-19 infection. This exploratory study seeks to dock the active components of Cannabis sativa, a natural plant with several pharmacological and biological properties, with the angiotensin-converting enzyme II (ACE2) receptor. A total of 3 C. sativa active components have been found to bind to the ACE2 protein active site and could inhibit spike binding, although they do not compete directly with the receptor-binding domain (RBD) of SARS-CoV-2. 6-Prenylapigenin, cannabivarin (CBN-C3), and Δ8-tetrahydrocannabinolic acid-A (Δ8-THCA) have a greater affinity (−8.3, −8.3, and −8.0 kcal/mol, respectively) and satisfactory interaction with ACE2 than its inhibitor MLN-4760 (−7.1 kcal/mol). These potential drugs with higher affinity for the ACE2 receptor and adequate absorption, distribution, metabolism, excretion, and toxicity (ADMET) values are candidates for treating or preventing SARS-CoV-2 infections. In vitro and in vivo investigations are needed to evaluate further the efficacy and toxicity of these hit compounds.
Digital Technology (DT) and Artificial Intelligence (AI) are of decisive importance for the understanding of the virus and the development of prevention and control measures. They can intervene in various fields, in particular, in the deployment of mathematical modeling to analyze the transmission of the virus, structural biology to identify the structure of the virus and develop vaccines, computational biology to study the evolution of the virus, as well as docking studies to screen for drugs. In this article, we will expose the role of new digital technologies to deal with the COVID-19 virus, by exposing certain applications as well as our scientific contribution which consists in applying an approach to analyze and study the three-dimensional structures of molecules, in particular, that of SARS-CoV-2 which generates Covid-19. Our method is a shape recognition algorithm based on the principle of the passage from the discrete to the continuous of entities. The results obtained demonstrated the performance of our algorithm in terms of response time and accuracy.
Background: Women with a cervicovaginal microbiota dominated by Lactobacillus spp. are at reduced risk of acquiring sexually transmitted infections including HIV but the biological mechanisms involved remain poorly defined. Here we performed metaproteomics on vaginal swab samples from young South African women (n=113) and transcriptomics analysis of cervicovaginal epithelial cell cultures to examine the ability of lactic acid, a metabolite produced by cervicovaginal lactobacilli, to modulate genital epithelial barrier function. Results: Compared to women with Lactobacillus -depleted microbiota, women dominated by vaginal lactobacilli exhibit higher abundance of bacterial lactate dehydrogenase, a key enzyme responsible for lactic acid production, which is independently associated with an increased abundance of epithelial barrier proteins. Physiological concentrations of lactic acid enhance epithelial cell culture barrier integrity and increase intercellular junctional molecule expression. Conclusions: These findings reveal a novel ability of vaginal lactic acid to enhance genital epithelial barrier integrity that may help prevent invasion by sexually transmitted pathogens.
The emergence of a novel coronavirus that later on rendered a global pandemic, caused desperation within the communities and drove increased interest in exploring medicinal plant–based therapeutics to treat and prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infections. Many medicinal plants have been reported to have antiviral, anti-inflammatory, and immunomodulatory effects that hinder, cure, or ease the symptoms of COVID-19 infection. This exploratory study seeks to dock the active components of Cannabis sativa , a natural plant with several pharmacological and biological properties, with the angiotensin-converting enzyme II (ACE2) receptor. A total of 3 C. sativa active components have been found to bind to the ACE2 protein active site and could inhibit spike binding, although they do not compete directly with the receptor-binding domain (RBD) of SARS-CoV-2. 6-Prenylapigenin, cannabivarin (CBN-C3), and Δ8-tetrahydrocannabinolic acid-A (Δ8-THCA) have a greater affinity (−8.3, −8.3, and −8.0 kcal/mol, respectively) and satisfactory interaction with ACE2 than its inhibitor MLN-4760 (−7.1 kcal/mol). These potential drugs with higher affinity for the ACE2 receptor and adequate absorption, distribution, metabolism, excretion, and toxicity (ADMET) values are candidates for treating or preventing SARS-CoV-2 infections. In vitro and in vivo investigations are needed to evaluate further the efficacy and toxicity of these hit compounds. Keywords Medicinal plant , , , COVID-19 , SARS-CoV-2 , ACE2 , spike , drug discovery , molecular docking , ADMET
An amendment to this paper has been published and can be accessed via the original article.
Female genital tract (FGT) inflammation is an important risk factor for HIV acquisition. The FGT microbiome is closely associated with inflammatory profile; however, the relative importance of microbial activities has not been established. Since proteins are key elements representing actual microbial functions, this study utilized metaproteomics to evaluate the relationship between FGT microbial function and inflammation in 113 young and adolescent South African women at high risk of HIV infection. Women were grouped as having low, medium, or high FGT inflammation by K-means clustering according to pro-inflammatory cytokine concentrations. A total of 3186 microbial and human proteins were identified in lateral vaginal wall swabs using liquid chromatography-tandem mass spectrometry, while 94 microbial taxa were included in the taxonomic analysis. Both metaproteomics and 16S rRNA gene sequencing analyses showed increased non-optimal bacteria and decreased lactobacilli in women with FGT inflammatory profiles. However, differences in the predicted relative abundance of most bacteria were observed between 16S rRNA gene sequencing and metaproteomics analyses. Bacterial protein functional annotations (gene ontology) predicted inflammatory cytokine profiles more accurately than bacterial relative abundance determined by 16S rRNA gene sequence analysis, as well as functional predictions based on 16S rRNA gene sequence data (p < 0.0001). The majority of microbial biological processes were underrepresented in women with high inflammation compared to those with low inflammation, including a Lactobacillus-associated signature of reduced cell wall organization and peptidoglycan biosynthesis. This signature remained associated with high FGT inflammation in a subset of 74 women 9 weeks later, was upheld after adjusting for Lactobacillus relative abundance, and was associated with in vitro inflammatory cytokine responses to Lactobacillus isolates from the same women. Reduced cell wall organization and peptidoglycan biosynthesis were also associated with high FGT inflammation in an independent sample of ten women. Both the presence of specific microbial taxa in the FGT and their properties and activities are critical determinants of FGT inflammation. Our findings support those of previous studies suggesting that peptidoglycan is directly immunosuppressive, and identify a possible avenue for biotherapeutic development to reduce inflammation in the FGT. To facilitate further investigations of microbial activities, we have developed the FGT-DB application that is available at http://fgtdb.org/ .
Following the publication of the first human genome, OMICs research, including genomics, transcriptomics, proteomics, and metagenomics, has been on the rise. OMICs studies revealed the complex genetic diversity among human populations and challenged our understandings of genotype-phenotype correlations. Africa, being the cradle of the first modern humans, is distinguished by a large genetic diversity within its populations and rich ethnolinguistic history. However, the available human OMICs tools and databases are not representative of this diversity, therefore creating significant gaps in biomedical research. African scientists, students, and publics are among the key contributors to OMICs systems science. This expert review examines the pressing issues in human OMICs research, education, and development in Africa, as seen through a lens of computational biology, public health relevant technology innovation, critically-informed science governance, and how best to harness OMICs data to benefit health and societies in Africa and beyond. We underscore the disparities between North and Sub-Saharan Africa at different levels. A harmonized African ethnolinguistic classification would help address annotation challenges associated with population diversity. Finally, building on the existing strategic research initiatives, such as the H3Africa and H3ABioNet Consortia, we highly recommend addressing large-scale multidisciplinary research challenges, strengthening research collaborations and knowledge transfer, and enhancing the ability of African researchers to influence and shape national and international research, policy, and funding agendas. This article and analysis contribute to a deeper understanding of past and current challenges in the African OMICs innovation ecosystem, while also offering foresight on future innovation trajectories.
COVID-19 is a pandemic infection of the respiratory system caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The viral ribonucleic acid (RNA) was found in many parts of the COVID-19 patients including the stool, suggesting a potential interaction with the host’s gut microbiome. The gut microbiome also plays major roles in immunity and inflammation. It also impacts pulmonary functions through the gut-lung axis. There have been recent reports of the importance of the host microbiome in infection and pathogenicity. The understanding of the gut and lung microbiomes would open the gate to new therapeutic approaches.
Over the last decade, it has become increasingly apparent that the microbiome is a central component in human well-being and illness. However, to establish innovative therapeutic methods, it is crucial to learn more about the microbiota. Thereby, the area of metagenomics and associated bioinformatics methods and tools has become considerable in the study of the human microbiome biodiversity. The application of these metagenomics approaches to studying the gut microbiome in COVID-19 patients could be one of the promising areas of research in the fight against the SARS-CoV-2 infection and disparity. Therefore, understanding how the gut microbiome is affected by or could affect the SARS-CoV-2 is very important. Herein, we present an overview of approaches and methods used in the current published studies on COVID-19 patients and the gut microbiome. The accuracy of these researches depends on the appropriate choice and the optimal use of the metagenomics bioinformatics platforms and tools. Interestingly, most studies reported that COVID-19 patients' microbiota are enriched with opportunistic microorganisms. The choice and use of appropriate computational tools and techniques to accurately investigate the gut microbiota is therefore critical in determining the appropriate microbiome profile for diagnosis and the most reliable antiviral or preventive microbial composition.
Researchers have long been presented with the challenge imposed by the role of genetic heterogeneity in drug response. For many years, Pharmacogenomics and pharmacomicrobiomics has been investigating the influence of an individual's genetic background to drug response and disposition. More recently, the human gut microbiome has proven to play a crucial role in the way patients respond to different therapeutic drugs and it has been shown that by understanding the composition of the human microbiome, we can improve the drug efficacy and effectively identify drug targets. However, our knowledge on the effect of host genetics on specific gut microbes related to variation in drug metabolizing enzymes, the drug remains limited and therefore limits the application of joint host-microbiome genome-wide association studies. In this paper, we provide a historical overview of the complex interactions between the host, human microbiome and drugs. While discussing applications, challenges and opportunities of these studies, we draw attention to the critical need for inclusion of diverse populations and the development of an innovative and combined pharmacogenomics and pharmacomicrobiomics approach, that may provide an important basis in personalized medicine.