is present in multiple hosts and environmental compartments as a normal inhabitant, temporary or persistent colonizer, and as a pathogen. Transmission of
between hosts and with the environment is ...considered to occur more often in areas with poor sanitation. We performed whole-genome comparative analyses on 60
isolates from soils and fecal sources (cattle, chickens, and humans) in households in rural Bangladesh. Isolates from household soils were in multiple branches of the reconstructed phylogeny, intermixed with isolates from fecal sources. Pairwise differences between all strain pairs were large (minimum, 189 single nucleotide polymorphisms SNPs), suggesting high diversity and heterogeneous origins of the isolates. The presence of multiple virulence and antibiotic resistance genes is indicative of the risk that
from soil and feces represent for the transmission of variants that pose potential harm to people. Analysis of the accessory genomes of the Bangladeshi
relative to
genomes available in NCBI identified a common pool of accessory genes shared among
isolates in this geographic area. Together, these findings indicate that in rural Bangladesh, a high level of
in soil is likely driven by contributions from multiple and diverse
sources (human and animal) that share an accessory gene pool relatively unique to previously published
genomes. Thus, interventions to reduce environmental pathogen or antimicrobial resistance transmission should adopt integrated One Health approaches that consider heterogeneous origins and high diversity to improve effectiveness and reduce prevalence and transmission.
is reported in high levels in household soil in low-income settings. When
reaches a soil environment, different mechanisms, including survival, clonal expansion, and genetic exchange, have the potential to either maintain or generate
variants with capabilities of causing harm to people. In this study, we used whole-genome sequencing to identify that
isolates collected from rural Bangladeshi household soils, including pathogenic and antibiotic-resistant variants, are diverse and likely originated from multiple diverse sources. In addition, we observed specialization of the accessory genome of this Bangladeshi
compared to
genomes available in current sequence databases. Thus, to address the high level of pathogenic and antibiotic-resistant
transmission in low-income settings, interventions should focus on addressing the heterogeneous origins and high diversity.
Abstract
Motivation
We present the Pangenome Analysis Toolkit (PATO) designed to simultaneously analyze thousands of genomes using a desktop computer. The tool performs common tasks of pangenome ...analysis such as core-genome definition and accessory genome properties and includes new features that help characterize population structure, annotate pathogenic features and create gene sharedness networks. PATO has been developed in R to integrate with the large set of tools available for genetic, phylogenetic and statistical analysis in this environment.
Results
PATO can perform the most demanding bioinformatic analyses in minutes with an accuracy comparable to state-of-the-art software but 20–30× times faster. PATO also integrates all the necessary functions for the complete analysis of the most common objectives in microbiology studies. Finally, PATO includes the necessary tools for visualizing the results and can be integrated with other analytical packages available in R.
Availabilityand implementation
The source code for PATO is freely available at https://github.com/irycisBioinfo/PATO under the GPLv3 license.
Supplementary information
Supplementary data are available at Bioinformatics online.
Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) ...with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor's microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.
Metabolic dysfunction-associated steatotic liver disease (MASLD), has emerged as an increasingly recognized problem among people living with HIV (PLWH). The gut-liver axis is considered to be ...strongly implicated in the pathogenesis of MASLD. We aimed to characterize the gut microbiota composition in PLWH and MASLD and compare it with that of two control groups: PLWH without MASLD and individuals with MASLD without HIV infection.
We collected clinical data and stool samples from participants. Bacterial 16S rRNA genes were amplified, sequenced, and clustered into operational taxonomic unit. Alpha diversity was studied by Shannon and Simpson indexes. To study how different the gut microbiota composition is between the different groups, beta diversity estimation was evaluated by principal coordinate analysis (PCoA) using Bray-Curtis dissimilarity. To further analyze differences in microbiome composition we performed a linear discriminant analysis (LDA) effect size (LEfSe).
We included 30 HIV
MASLD
, 30 HIV
MASLD
and 20 HIV
MASLD
participants. Major butyrate producers, including
,
, and
dominated the microbiota in all three groups. Shannon's and Simpson's diversity metrics were higher among MASLD
individuals (Kruskal-Wallis p = 0.047). Beta diversity analysis showed distinct clustering in MASLD
, with MASLD
participants overlapping regardless of HIV status (ADONIS significance <0.001). MASLD was associated with increased homogeneity across individuals, in contrast to that observed in the HIV+NAFDL- group, in which the dispersion was higher (Permanova test, p value <0.001; ANOSIM, p value <0.001). MASLD but not HIV determined a different microbiota structure (HIV
vs. HIV
MASLD
, q-value = 0.002; HIV
MASLD
vs. HIV
MASLD
, q-value = 0.930; and HIV
MASLD
vs. HIV
MASLD
, q-value < 0.001). The most abundant genera in MASLD- were
, and
. In contrast, the most enriched genera in MASLD+ were
, and
We found a microbiome signature linked to MASLD, which had a greater influence on the overall structure of the gut microbiota than HIV status alone.
While changes in microbiome composition have been associated with HIV, the effect of diet and its potential impact on inflammation remains unclear. Methods: Twenty-seven people living with HIV (PWH) ...on antiretroviral therapy (ART) were studied. A comprehensive dietary analysis was performed and two types of dietary patterns were determined. We explored the associations of each dietary pattern with gut microbiota and plasma inflammatory biomarkers. Results: We appreciated two dietary patterns, Mediterranean-like (MEL) and one Western-like (WEL). Compared to participants with the WEL pattern, participants with MEL pattern showed higher abundance of Lachnospira (p-value = 0.02) and lower levels of the inflammatory biomarkers D-dimer (p-value = 0.050) and soluble TNF-alpha receptor 2 (sTNFR2) (p-value = 0.049). Men who have sex with men (MSM) with MEL pattern had lower abundance of Erysipelotrichaceae (p-value < 0.001) and lower levels of D-dimer (p-value = 0.026) than MSM with WEL pattern. Conclusion: MEL pattern favours Lachnospira abundance, and protects against Erysipelotrichaceae abundance and higher levels of the inflammatory biomarkers D-dimer and sTNFR2, precursors of inflammatory processes in HIV-infected patients. Our study contributes to understanding the determinants of a healthier diet and its connections with gut microbiota and inflammation.
Abstract
Background
While the microbiota has been associated with human papillomavirus malignant transformation, it is unclear whether anal bacteria could improve the low specificity of anal cytology ...for the screening of high-grade intraepithelial squamous neoplasia (HSIL)
Methods
We recruited men who have sex with men undergoing anal cytology and high-resolution anoscopy. We assessed the microbiota composition from fecal samples and cytobrush anal samples using 16S ribosomal DNA sequencing in participants with or without biopsy-proven HSIL (bHSIL). We selected bacterial biomarkers based on their linear discriminant analysis. We assessed their predictive performance using logistic regression and bootstrap resampling.
Results
We included 128 individuals, 47 (36.7%) with bHSIL and 99 (77.3%) with human immunodeficiency virus. We detected 40 potential predictors of bHSIL. Ruminococcaceae NK4A214 group, Alloprevotella genus, Prevotella melanonigenica, and Ruminococcaceae UCG-014 were the most predictive of bHSIL. From 35 false-positive cytologic results, the combination of these 4 biomarkers with the anal cytology reclassified to true-negative 33 individuals (94%) and showed good diagnostic performance (area under the receiver operating characteristic curve, 0.805; 95% confidence interval, .728–.882).
Conclusions
We found anal-associated bacteria indicative of a higher risk of precancerous anal lesions, which combination was highly specific. The microbiota could be developed as a complementary diagnostic tool to overcome the limitations of the current screening strategy for anal cancer.
We here propose a set of bacterial biomarkers indicative of a higher risk of precancerous anal lesions, which combination was highly specific. Our findings indicate that the microbiota could be developed as a complementary diagnostic tool for anal cancer screening.
Abstract
Human immunodeficiency virus (HIV) infection impairs mucosal immunity and leads to bacterial translocation, fueling chronic inflammation and disease progression. While this is well ...established, questions remain about the compositional profile of the translocated bacteria, and to what extent it is influenced by antiretroviral therapy (ART). Using 16S ribosomal DNA targeted sequencing and shotgun proteomics, we showed that HIV increases bacterial translocation from the gut to the blood. HIV increased alpha diversity in the blood, which was dominated by aerobic bacteria belonging to Micrococcaceae (Actinobacteria) and Pseudomonadaceae (Proteobacteria) families, and the number of circulating bacterial proteins was also increased. Forty-eight weeks of ART attenuated this phenomenon. We found that enrichment with Lactobacillales order, and depletion of Actinobacteria class and Moraxellaceae and Corynebacteriacae families, were significantly associated with greater immune recovery and correlated with several inflammatory markers. Our findings suggest that the molecular cross talk between the host and the translocated bacterial products could influence ART-mediated immune recovery.
In this longitudinal study in human immunodeficiency virus (HIV)–infected individuals, we found a specific signature of bacterial circulating DNA sequences and proteins, suggesting that molecular cross talk between host and translocated bacterial products could influence antiretroviral therapy–mediated immune recovery.
Despite its high prevalence, the mechanisms underlying non-alcoholic fatty liver disease (NAFLD) in people living with HIV (PLWH) are still unclear. In this prospective cohort study, we aim to ...evaluate differences in plasma fatty acid profiles between HIV-infected and HIV-uninfected participants with NAFLD. We included participants diagnosed with NAFLD, both HIV-infected and HIV-uninfected. Fatty acid methyl esters were measured from plasma samples. Ratios (product/substrate) were used to estimate desaturases and elongases activity. We used linear regression for adjusted analyses. We included 31 PLWH and 22 HIV-uninfected controls. We did not find differences in the sum of different types of FA or in FA with a greater presence of plasma. However, there were significant differences in the distribution of some FA, with higher concentrations of ALA, trans-palmitoleic, and behenic acids, and a lower concentration of lignoceric acid in PLWH. PLWH had lower C24:0/C22:0 and C16:0/C14:0 ratios, which estimates the activity of elongases ELOVL1 and ELOVL6. Both groups had similar fatty acid distribution, despite differences in traditional risk factors. PLWH had a lower proportion of specific ratios that estimate ELOVL1 and ELOVL6 activity, which had been previously described for other inflammatory conditions, such as psoriasis.
The gut microbiota exerts a critical influence in the immune system. The gut microbiota of human virus immunodeficiency (HIV)-infected children remains barely explored. We aimed to characterize the ...fecal microbiota in vertically HIV-infected children and to explore the effects of its modulation with a symbiotic nutritional intervention.
a pilot, double blind, randomized placebo-controlled study including HIV-infected children who were randomized to receive a nutritional supplementation including prebiotics and probiotics or placebo for four weeks. HIV-uninfected siblings were recruited as controls. The V3-V4 region of the 16S rRNA gene was sequenced in fecal samples.
22 HIV-infected children on antiretroviral therapy (ART) and with viral load (VL) <50/mL completed the follow-up period. Mean age was 11.4 ± 3.4 years, eight (32%) were male. Their microbiota showed reduced alpha diversity compared to controls and distinct beta diversity at the genus level (Adonis
= 0.042). Patients showed decreased abundance of commensals
and an increase in
and
The nutritional intervention shaped the microbiota towards the control group, without a clear directionality.
Vertical HIV infection is characterized by changes in gut microbiota structure, distinct at the compositional level from the findings reported in adults. A short nutritional intervention attenuated bacterial dysbiosis, without clear changes at the community level.
In a group of 24 vertically HIV-infected children, in comparison to 11 uninfected controls, intestinal dysbiosis was observed despite effective ART. Although not fully effective to restore the microbiota, a short intervention with pre/probiotics attenuated bacterial dysbiosis.
While the intestinal microbiome seems a major driver of persistent immune defects in people with HIV (PWH), little is known about its fungal component, the mycobiome. We assessed the inter-kingdom ...mycobiome-bacteriome interactions, the impact of diet, and the association with the innate and adaptive immunity in PWH on antiretroviral therapy. We included 24 PWH individuals and 12 healthy controls. We sequenced the Internal Transcribed Spacer 2 amplicons, determined amplicon sequence variants, measured biomarkers of the innate and adaptive immunity in blood and relations with diet. Compared to healthy controls, PWH subjects exhibited a distinct and richer mycobiome and an enrichment for Debaryomyces hansenii, Candida albicans, and Candida parapsilosis. In PWH, Candida and Pichia species were strongly correlated with several bacterial genera, including Faecalibacterium genus. Regarding the links between the mycobiome and systemic immunology, we found a positive correlation between Candida species and the levels of proinflammatory cytokines (sTNF-R2 and IL-17), interleukin 22 (a cytokine implicated in the regulation of mucosal immunity), and CD8+ T cell counts. This suggests an important role of the yeasts in systemic innate and adaptive immune responses. Finally, we identified inter-kingdom interactions implicated in fiber degradation, short-chain fatty acid production, and lipid metabolism, and an effect of vegetable and fiber intake on the mycobiome. Therefore, despite the great differences in abundance and diversity between the bacterial and fungal communities of the gut, we defined the changes associated with HIV, determined several different inter-kingdom associations, and found links between the mycobiome, nutrient metabolism, and systemic immunity.
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