COVID-19 infection may predispose to secondary bacterial infection which is associated with poor clinical outcome especially among critically ill patients. We aimed to characterize the lower ...respiratory tract bacterial microbiome of COVID-19 critically ill patients in comparison to COVID-19-negative patients. We performed a 16S rRNA profiling on bronchoalveolar lavage (BAL) samples collected between April and May 2020 from 24 COVID-19 critically ill subjects and 24 patients with non-COVID-19 pneumonia. Lung microbiome of critically ill patients with COVID-19 was characterized by a different bacterial diversity (PERMANOVA on weighted and unweighted UniFrac Pr(> F) = 0.001) compared to COVID-19-negative patients with pneumonia. Pseudomonas alcaligenes, Clostridium hiranonis, Acinetobacter schindleri, Sphingobacterium spp., Acinetobacter spp. and Enterobacteriaceae, characterized lung microbiome of COVID-19 critically ill patients (LDA score > 2), while COVID-19-negative patients showed a higher abundance of lung commensal bacteria (Haemophilus influenzae, Veillonella dispar, Granulicatella spp., Porphyromonas spp., and Streptococcus spp.). The incidence rate (IR) of infections during COVID-19 pandemic showed a significant increase of carbapenem-resistant Acinetobacter baumannii (CR-Ab) infection. In conclusion, SARS-CoV-2 infection and antibiotic pressure may predispose critically ill patients to bacterial superinfection due to opportunistic multidrug resistant pathogens.
Understanding gut microbiome functions requires cultivated bacteria for experimental validation and reference bacterial genome sequences to interpret metagenome datasets and guide functional ...analyses. We present the Human Gastrointestinal Bacteria Culture Collection (HBC), a comprehensive set of 737 whole-genome-sequenced bacterial isolates, representing 273 species (105 novel species) from 31 families found in the human gastrointestinal microbiota. The HBC increases the number of bacterial genomes derived from human gastrointestinal microbiota by 37%. The resulting global Human Gastrointestinal Bacteria Genome Collection (HGG) classifies 83% of genera by abundance across 13,490 shotgun-sequenced metagenomic samples, improves taxonomic classification by 61% compared to the Human Microbiome Project (HMP) genome collection and achieves subspecies-level classification for almost 50% of sequences. The improved resource of gastrointestinal bacterial reference sequences circumvents dependence on de novo assembly of metagenomes and enables accurate and cost-effective shotgun metagenomic analyses of human gastrointestinal microbiota.
Human-to-human transmission of symbiotic, anaerobic bacteria is a fundamental evolutionary adaptation essential for membership of the human gut microbiota. However, despite its importance, the ...genomic and biological adaptations underpinning symbiont transmission remain poorly understood. The Firmicutes are a dominant phylum within the intestinal microbiota that are capable of producing resistant endospores that maintain viability within the environment and germinate within the intestine to facilitate transmission. However, the impact of host transmission on the evolutionary and adaptive processes within the intestinal microbiota remains unknown.
We analyze 1358 genomes of Firmicutes bacteria derived from host and environment-associated habitats. Characterization of genomes as spore-forming based on the presence of sporulation-predictive genes reveals multiple losses of sporulation in many distinct lineages. Loss of sporulation in gut Firmicutes is associated with features of host-adaptation such as genome reduction and specialized metabolic capabilities. Consistent with these data, analysis of 9966 gut metagenomes from adults around the world demonstrates that bacteria now incapable of sporulation are more abundant within individuals but less prevalent in the human population compared to spore-forming bacteria.
Our results suggest host adaptation in gut Firmicutes is an evolutionary trade-off between transmission range and colonization abundance. We reveal host transmission as an underappreciated process that shapes the evolution, assembly, and functions of gut Firmicutes.
•Candida spp. colonization was higher in patients with COVID-19 than in those without COVID-19.•• ARDS in COVID-19 was characterized by lung dysbiosis and decreased fungal diversity.•• Ascomycota was ...more represented in patients with COVID-19 not colonized with Candida spp.
The COVID-19 pandemic has intensified interest in how the infection affects the lung microbiome of critically ill patients and how it contributes to acute respiratory distress syndrome (ARDS). We aimed to characterize the lower respiratory tract mycobiome of critically ill patients with COVID-19 in comparison to patients without COVID-19.
We performed an internal transcribed spacer 2 (ITS2) profiling with the Illumina MiSeq platform on 26 respiratory specimens from patients with COVID-19 as well as from 26 patients with non–COVID-19 pneumonia.
Patients with COVID-19 were more likely to be colonized with Candida spp. ARDS was associated with lung dysbiosis characterized by a shift to Candida species colonization and a decrease of fungal diversity. We also observed higher bacterial phylogenetic distance among taxa in colonized patients with COVID-19. In patients with COVID-19 not colonized with Candida spp., ITS2 amplicon sequencing revealed an increase of Ascomycota unassigned spp. and 1 Aspergillus spp.–positive specimen. In addition, we found that corticosteroid therapy was frequently associated with positive Galactomannan cell wall component of Aspergillus spp. among patients with COVID-19.
Our study underpins that ARDS in patients with COVID-19 is associated with lung dysbiosis and that an increased density of Ascomycota unassigned spp. is present in patients not colonized with Candida spp.
Bacterial speciation is a fundamental evolutionary process characterized by diverging genotypic and phenotypic properties. However, the selective forces that affect genetic adaptations and how they ...relate to the biological changes that underpin the formation of a new bacterial species remain poorly understood. Here, we show that the spore-forming, healthcare-associated enteropathogen Clostridium difficile is actively undergoing speciation. Through large-scale genomic analysis of 906 strains, we demonstrate that the ongoing speciation process is linked to positive selection on core genes in the newly forming species that are involved in sporulation and the metabolism of simple dietary sugars. Functional validation shows that the new C. difficile produces spores that are more resistant and have increased sporulation and host colonization capacity when glucose or fructose is available for metabolism. Thus, we report the formation of an emerging C. difficile species, selected for metabolizing simple dietary sugars and producing high levels of resistant spores, that is adapted for healthcare-mediated transmission.
The menopausal transition marks a significant physiological shift in women. Menopause-related symptoms can significantly affect a woman's quality of life and probiotics have emerged as a promising ...avenue. This study aims to investigate the benefits of probiotics in improving vaginal well-being and microbiota composition in post-menopausal women. A prospective observational clinical trial was carried out enrolling 50 post-menopausal healthy women, aged between 45 and 65 years old, taking a supplement containing
PBS067,
subsp.
BL050, and
LRH020 (3B CFU/day) for 28 days. Vaginal swabs were collected to evaluate microbiota fluctuation and the inflammatory pattern was recorded. A Vaginal Health Index was provided to evaluate vaginal well-being throughout the trial. Clinical outcomes revealed a decrease in menopausal symptoms. Significant improvements were observed across various parameters: a 50% enhancement in the VHI score (
< 0.0001), alongside substantial reductions in inflammatory cytokine levels. An 87.8% decrease in IL-6, 57.6% in IL-1β, and 40.8% in TNF-α was observed (
< 0.05). Moreover, the probiotic intervention facilitated the restoration of vaginal microbiota, evidenced by an increase in lactobacilli abundance. In conclusion, the combination of these specific probiotic strains, previously clinically tested in childbearing-age women, showed to be effective also for post-menopausal women.
COVID-19, whose causative pathogen is the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), was declared a pandemic in March 2020. The gastrointestinal tract is one of the targets of this ...virus, and mounting evidence suggests that gastrointestinal symptoms may contribute to disease severity. The gut-lung axis is involved in the immune response to SARS-CoV-2; therefore, we investigated whether COVID-19 patients' bacterial and fungal gut microbiome composition was linked to disease clinical outcome.
In May 2020, we collected stool samples and patient records from 24 hospitalized patients with laboratory-confirmed SARS-CoV-2 infection. Fungal and bacterial gut microbiome was characterized by amplicon sequencing on the MiSeq, Illumina's integrated next generation sequencing instrument. A cohort of 201 age- and sex-matched healthy volunteers from the project PRJNA661289 was used as a control group for the bacterial gut microbiota analysis.
We observed that female COVID-19 patients had a lower gut bacterial microbiota richness than male patients, which was consistent with a different latency in hospital admittance time between the two groups. Both sexes in the COVID-19 patient study group displayed multiple positive associations with opportunistic bacterial pathogens such as
,
, and
. Of note, the
genus dominated the gut mycobiota of COVID-19 patients, and adult patients showed a higher intestinal fungal diversity than elderly patients. We found that
fungal genera were positively associated with bacterial short-chain fatty acid (SCFA) producers and negatively associated with the proinflammatory genus
in COVID-19 patients, and we observed that none of the patients who harbored it were admitted to the high-intensity unit.
COVID-19 was associated with opportunistic bacterial pathogens, and
was the dominant fungal taxon in the intestine. Together, we found an association between commensal SCFA-producers and a fungal genus that was present in the intestines of patients who did not experience the most severe outcome of the disease. We believe that this taxon could have played a role in the disease outcome, and that further studies should be conducted to understand the role of fungi in gastrointestinal and health protection.
There is a wide array of evidence across species that exposure to antibiotics is associated with dysbiosis, and due to their widespread use, this also raises concerns also in medicine. The study ...aimed to determine the changes on the fecal microbiota in hospitalized neonatal foals administered with broad-spectrum antimicrobials and supplemented probiotics. Fecal samples were collected at hospital admission (Ta), at the end of the antimicrobial treatment (Te) and at discharge (Td). Feces were analysed by next-generation sequencing of the 16S rRNA gene on Illumina MiSeq. Seven foals treated with IV ampicillin and amikacin/gentamicin were included. The mean age at Ta was 19 h, the mean treatment length was 7 days and the mean time between Te and Td was 4.3 days. Seven phyla were identified: Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, Proteobacteria, TM7 and Verrucomicrobia. At Ta, Firmicutes (48.19%) and Proteobacteria (31.56%) were dominant. The alpha diversity decreased from Ta to Te, but it was the highest at Td. The beta diversity was higher at Ta than at Te and higher at Td than at Te. An increase in Akkermansia over time was detected. The results suggest that the intestinal microbiota of neonatal foals rapidly returns to a high diversity after treatment. It is possible that in foals, the effect of antimicrobials is strongly influenced or overshadowed by the time-dependent changes in the developing gut microbiota.
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•Gut dysbiosis correlated with systemic inflammation in COVID-19 patients.•Dysbiosis in COVID-19 patients was antibiotic-independent.•Oral tannins reduced systemic inflammation but ...was not clinically efficacious.•Tannins inhibited MIP-1α, which negatively correlated with Bifidobacterium abundance.
The clinical study aim was to investigate whether a tannin-based dietary supplementation could improve the efficacy of standard-of-care treatment of hospitalized COVID-19 patients by restoring gut microbiota function. Adverse events and immunomodulation post-tannin supplementation were also investigated. A total of 124 patients receiving standard-of-care treatment were randomized to oral tannin-based supplement or placebo for a total of 14 days. Longitudinal blood and stool samples were collected for cytokine and 16S rDNA microbiome profiling, and results were compared with 53 healthy controls. Although oral tannin supplementation did not result in clinical improvement or significant gut microbiome shifts after 14-days, a reduction in the inflammatory state was evident and significantly correlated with microbiota modulation. Among cytokines measured, MIP-1α was significantly decreased with tannin treatment (p = 0.03) where it correlated positively with IL-1β and TNF- α, and negatively with stool Bifidobacterium abundance.
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