Fecal metabolite profiling identifies critically ill patients with increased 30-day mortality

Critically ill patients admitted to the medical intensive care unit (MICU) have reduced intestinal microbiota diversity and altered microbiome-associated metabolite concentrations. Metabolites produced by the gut microbiota have been associated with survival of patients receiving complex medical treatments and thus might represent a treatable trait to improve clinical outcomes. We prospectively collected fecal specimens, defined microbiome compositions by shotgun metagenomic sequencing, and quantified microbiota-derived fecal metabolites by mass spectrometry from 196 critically ill patients admitted to the MICU for non–COVID-19 respiratory failure or shock to correlate microbiota features and metabolites with 30-day mortality. Microbiota compositions of the first fecal sample after MICU admission did not independently associate with 30-day mortality. We developed a metabolic dysbiosis score (MDS) that uses fecal concentrations of 13 microbiota-derived metabolites, which predicted 30-day mortality independent of known confounders. The MDS complements existing tools to identify patients at high risk of mortality by incorporating potentially modifiable, microbiome-related, independent contributors to host resilience

Novel translational approaches to the search for precision therapies for acute respiratory distress syndrome.

In the 50 years since acute respiratory distress syndrome (ARDS) was first described, substantial progress has been made in identifying the risk factors for and the pathogenic contributors to the syndrome and in characterising the protein expression patterns in plasma and bronchoalveolar lavage fluid from patients with ARDS. Despite this effort, however, pharmacological options for ARDS remain scarce. Frequently cited reasons for this absence of specific drug therapies include the heterogeneity of patients with ARDS, the potential for a differential response to drugs, and the possibility that the wrong targets have been studied. Advances in applied biomolecular technology and bioinformatics have enabled breakthroughs for other complex traits, such as cardiovascular disease or asthma, particularly when a precision medicine paradigm, wherein a biomarker or gene expression pattern indicates a patient's likelihood of responding to a treatment, has been pursued. In this Review, we consider the biological and analytical techniques that could facilitate a precision medicine approach for ARDS

Gut microbiota and its metabolic products in acute respiratory distress syndrome

The prevalence rate of acute respiratory distress syndrome (ARDS) is estimated at approximately 10% in critically ill patients worldwide, with the mortality rate ranging from 17% to 39%. Currently, ARDS mortality is usually higher in patients with COVID-19, giving another challenge for ARDS treatment. However, the treatment efficacy for ARDS is far from satisfactory. The relationship between the gut microbiota and ARDS has been substantiated by relevant scientific studies. ARDS not only changes the distribution of gut microbiota, but also influences intestinal mucosal barrier through the alteration of gut microbiota. The modulation of gut microbiota can impact the onset and progression of ARDS by triggering dysfunctions in inflammatory response and immune cells, oxidative stress, cell apoptosis, autophagy, pyroptosis, and ferroptosis mechanisms. Meanwhile, ARDS may also influence the distribution of metabolic products of gut microbiota. In this review, we focus on the impact of ARDS on gut microbiota and how the alteration of gut microbiota further influences the immune function, cellular functions and related signaling pathways during ARDS. The roles of gut microbiota-derived metabolites in the development and occurrence of ARDS are also discussed

The Microbiota of the Extremely Preterm Infant.

Colonization of the extremely preterm infant's gastrointestinal tract and skin begins in utero and is influenced by a variety of factors, the most important including gestational age and environmental exposures. The composition of the intestinal and skin microbiota influences the developing innate and adaptive immune responses with short-term and long-term consequences including altered risks for developing necrotizing enterocolitis, sepsis, and a wide variety of microbe-related diseases of children and adults. Alteration of the composition of the microbiota to decrease disease risk is particularly appealing for this ultra-high-risk cohort that is brand new from an evolutionary standpoint

The relationship between gut and nasopharyngeal microbiome composition can predict the severity of COVID-19

Coronavirus disease 2019 (COVID-19) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that displays great variability in clinical phenotype. Many factors have been described to be correlated with its severity, and microbiota could play a key role in the infection, progression, and outcome of the disease. SARS-CoV-2 infection has been associated with nasopharyngeal and gut dysbiosis and higher abundance of opportunistic pathogens. To identify new prognostic markers for the disease, a multicentre prospective observational cohort study was carried out in COVID-19 patients divided into three cohorts based on symptomatology: mild (n = 24), moderate (n = 51), and severe/critical (n = 31). Faecal and nasopharyngeal samples were taken, and the microbiota was analysed. Linear discriminant analysis identified Mycoplasma salivarium, Prevotella dentalis, and Haemophilus parainfluenzae as biomarkers of severe COVID-19 in nasopharyngeal microbiota, while Prevotella bivia and Prevotella timonensis were defined in faecal microbiota. Additionally, a connection between faecal and nasopharyngeal microbiota was identified, with a significant ratio between P. timonensis (faeces) and P. dentalis and M. salivarium (nasopharyngeal) abundances found in critically ill patients. This ratio could serve as a novel prognostic tool for identifying severe COVID-19 cases.Peer reviewe

The relationship between gut and nasopharyngeal microbiome composition can predict the severity of COVID-19

Background: Coronavirus disease 2019 (COVID-19) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that displays great variability in clinical phenotype. Many factors have been described to be correlated with its severity but no specific determinants of infection outcome have been identified yet, maybe due the complex pathogenic mechanisms. The microbiota could play a key role in the infection and in the progression and outcome of the disease. Hence, SARS-CoV-2 infection has been associated with nasopharyngeal and gut dysbiosis and higher abundance of opportunistic pathogens. Methods: To identify new prognostic markers for the disease, a multicenter prospective observational cohort study was carried out in COVID-19 patients that were divided in three cohorts according to their symptomatology: mild (n=24), moderate (n=51) and severe/critical (n=31). Faecal and nasopharyngeal samples were taken and the microbiota was analysed. Results: Microbiota composition could be associated with the severity of the symptoms and the linear discriminant analysis identified the genera Mycoplasma and Prevotella as severity biomarkers in nasopharyngeal samples, and Allistipes, Enterococcus and Escherichia in faecal samples. Moreover, M. salivarium was defined as a unique microorganism in COVID-19 patients' nasopharyngeal microbiota while P. bivia and P. timonensis were defined in faecal microbiota. A connection between faecal and nasopharyngeal microbiota in COVID-19 patients was also identified as a strong positive correlation between P. timonensis (faeces) towards P. dentalis and M. salivarium(nasopharyngeal) was found in critically ill patients. Conclusions: This ratio could be used as a novel prognostic biomarker for severe COVID-19 patients.The research project was sup-ported by Government of Andalucia (Spain) (CV20-99908).N

Gut microbiota composition during hospitalization is associated with 60-day mortality after severe COVID-19

Background - Gut microbiota alterations have been reported in hospitalized COVID-19 patients, with reduced alpha diversity and altered microbiota composition related to respiratory failure. However, data regarding gut microbiota and mortality are scarce. Methods - Rectal swabs for gut microbiota analyses were collected within 48 h after hospital admission (baseline; n = 123) and three-month post-admission (n = 50) in a subset of patients included in the Norwegian SARS-CoV2 cohort study. Samples were analysed by sequencing the 16S rRNA gene. Gut microbiota diversity and composition at baseline were assessed in relation to need for intensive care unit (ICU) admission during hospitalization. The primary objective was to investigate whether the ICU-related gut microbiota was associated with 60-day mortality. Results - Gut microbiota diversity (Shannon index) at baseline was lower in COVID-19 patients requiring ICU admission during hospitalization than in those managed in general wards. A dysbiosis index representing a balance of enriched and reduced taxa in ICU compared with ward patients, including decreased abundance of butyrate-producing microbes and enrichment of a partly oral bacterial flora, was associated with need of ICU admission independent of antibiotic use, dexamethasone use, chronic pulmonary disease, PO2/FiO2 ratio, C-reactive protein, neutrophil counts or creatinine levels (adjusted p  Conclusions - Although our data should be regarded as exploratory due to low number of clinical end points, they suggest that gut microbiota alterations during hospitalization could be related to poor prognosis after severe COVID-19. Larger studies of gut involvement during COVID-19 in relation to long-term clinical outcome are warranted

Gut Microbiota Composition Can Predict Colonization by Multidrug-Resistant Bacteria in SARS-CoV-2 Patients in Intensive Care Unit: A Pilot Study

The SARS-CoV-2 infection has increased the number of patients entering Intensive Care Unit (ICU) facilities and antibiotic treatments. Concurrently, the multi-drug resistant bacteria (MDRB) colonization index has risen. Considering that most of these bacteria are derived from gut microbiota, the study of its composition is essential. Additionally, SARS-CoV-2 infection may promote gut dysbiosis, suggesting an effect on microbiota composition. This pilot study aims to determine bacteria biomarkers to predict MDRB colonization risk in SARS-CoV-2 patients in ICUs. Seventeen adult patients with an ICU stay >48 h and who tested positive for SARS-CoV-2 infection were enrolled in this study. Patients were assigned to two groups according to routine MDRB colonization surveillance: non-colonized and colonized. Stool samples were collected when entering ICUs, and microbiota composition was determined through Next Generation Sequencing techniques. Gut microbiota from colonized patients presented significantly lower bacterial diversity compared with non-colonized patients (p < 0.05). Microbiota in colonized subjects showed higher abundance of Anaerococcus, Dialister and Peptoniphilus, while higher levels of Enterococcus, Ochrobactrum and Staphylococcus were found in non-colonized ones. Moreover, LEfSe analysis suggests an initial detection of Dialister propionicifaciens as a biomarker of MDRB colonization risk. This pilot study shows that gut microbiota profile can become a predictor biomarker for MDRB colonization in SARS-CoV-2 patients.Junta de Andalucía (CTS 164; CV20-77708)Instituto de Salud Carlos III (PI19/01058; PI20/01447Fundación Andaluza de Farmacia Hospitalaria” (3095/2020)

Gut and airway microbiota dysbiosis and their role in COVID-19 and long-COVID

The gut microbiota plays a crucial role in human health and disease. Gut dysbiosis is known to be associated with increased susceptibility to respiratory diseases and modifications in the immune response and homeostasis of the lungs (the so-called gut-lung axis). Furthermore, recent studies have highlighted the possible role of dysbiosis in neurological disturbances, introducing the notion of the "gut-brain axis." During the last 2 years, several studies have described the presence of gut dysbiosis during coronavirus disease 2019 (COVID-19) and its relationship with disease severity, SARS-CoV-2 gastrointestinal replication, and immune inflammation. Moreover, the possible persistence of gut dysbiosis after disease resolution may be linked to long-COVID syndrome and particularly to its neurological manifestations. We reviewed recent evidence on the association between dysbiosis and COVID-19, investigating the possible epidemiologic confounding factors like age, location, sex, sample size, the severity of disease, comorbidities, therapy, and vaccination status on gut and airway microbial dysbiosis in selected studies on both COVID-19 and long-COVID. Moreover, we analyzed the confounding factors strictly related to microbiota, specifically diet investigation and previous use of antibiotics/probiotics, and the methodology used to study the microbiota (alpha- and beta-diversity parameters and relative abundance tools). Of note, only a few studies focused on longitudinal analyses, especially for long-term observation in long-COVID. Lastly, there is a lack of knowledge regarding the role of microbiota transplantation and other therapeutic approaches and their possible impact on disease progression and severity. Preliminary data seem to suggest that gut and airway dysbiosis might play a role in COVID-19 and in long-COVID neurological symptoms. Indeed, the development and interpretation of these data could have important implications for future preventive and therapeutic strategies