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Critical illness can significantly alter the composition and function of the human microbiome, but few studies have examined these changes over time. Here, we conduct a comprehensive analysis of the oral, lung, and gut microbiota in 479 mechanically ventilated patients (223 females, 256 males) with acute respiratory failure. We use advanced DNA sequencing technologies, including Illumina amplicon sequencing (utilizing 16S and ITS rRNA genes for bacteria and fungi, respectively, in all sample types) and Nanopore metagenomics for lung microbiota. Our results reveal a progressive dysbiosis in all three body compartments, characterized by a reduction in microbial diversity, a decrease in beneficial anaerobes, and an increase in pathogens. We find that clinical factors, such as chronic obstructive pulmonary disease, immunosuppression, and antibiotic exposure, are associated with specific patterns of dysbiosis. Interestingly, unsupervised clustering of lung microbiota diversity and composition by 16S independently predicted survival and performed better than traditional clinical and host-response predictors. These observations are validated in two separate cohorts of COVID-19 patients, highlighting the potential of lung microbiota as valuable prognostic biomarkers in critical care. Understanding these microbiome changes during critical illness points to new opportunities for microbiota-targeted precision medicine interventions. Here, the authors profile the oral, lung, and gut microbiota of 479 patients with acute respiratory failure, revealing that reduced diversity and increased pathogen presence can predict survival outcomes, highlighting the potential for microbiota-based approaches in critical care. [ABSTRACT FROM AUTHOR]

Background: The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional alterations in severe COVID-19, defined as acute respiratory or other organ failure. Methods: We profiled 127 hospitalized patients with COVID-19 (n = 79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites. Results: Forty-eight species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis, each previously linked to post-acute COVID syndrome or "long COVID," suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with classifying whether stool was obtained from patients with severe vs. moderate COVID-19, a finding that was externally validated in an independent cohort. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease. Conclusions: Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to expand upon these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background: Intestinal ischemia/reperfusion (I/R) causes barrier impairment and bacterial influx. Protection against I/R injury in sterile organs by hypoxic preconditioning (HPC) had been attributed to erythropoietic and angiogenic responses. Our previous study showed attenuation of intestinal I/R injury by HPC for 21 days in a neutrophil-dependent manner.Aim: To investigate the underlying mechanisms of neutrophil priming by HPC, and explore whether adoptive transfer of primed neutrophils is sufficient to ameliorate intestinal I/R injury.Methods: Rats raised in normoxia (NM) and HPC for 3 or 7 days were subjected to sham operation or superior mesenteric artery occlusion for I/R challenge. Neutrophils isolated from rats raised in NM or HPC for 21 days were intravenously injected into naïve controls prior to I/R.Results: Similar to the protective effect of HPC-21d, I/R-induced mucosal damage was attenuated by HPC-7d but not by HPC-3d. Naïve rats reconstituted with neutrophils of HPC-21d rats showed increase in intestinal phagocytic infiltration and myeloperoxidase activity, and barrier protection against I/R insult. Elevated free radical production, and higher bactericidal and phagocytic activity were observed in HPC neutrophils compared to NM controls. Moreover, increased serum levels of tumor necrosis factor α (TNFα) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) were seen in HPC rats. Naïve neutrophils incubated with HPC serum or recombinant TNFα, but not CINC-1, exhibited heightened respiratory burst and bactericidal activity. Lastly, neutrophil priming effect was abolished by neutralization of TNFα in HPC serum.Conclusions: TNFα-primed neutrophils by HPC act as effectors cells for enhancing barrier integrity under gut ischemia. [ABSTRACT FROM AUTHOR]

Acute sleep deprivation (ASD) is often observed in shift workers and characterized by drowsiness and unrelenting exhaustion. The physiological and psychological effects of ASD include anxiety, depression, cognitive impairment, systemic inflammation, stress responses, and disruptions of gut microbiota. However, the mechanisms involved in the ASD-associated circadian dysregulations with regard to gut dysbiosis, systemic inflammation, physiological modulation, and psychiatry disorders remain unclear. The aim of this study was to investigate whether central nervous system disorders induced by ASD are related to inflammation, barrier dysfunction, and circadian dysregulation. We also assessed impacts on microbiota succession. Male C57BL/6 mice were randomly allocated to the control and sleep deprivation (SD) groups. Mice in the SD group were subjected to 72 h of paradoxical SD using the modified multiple-platform method for ASD induction (72 h rapid eye movement-SD). The effects of ASD on dietary consumption, behaviors, cytokines, microbiota, and functional genes were determined. The appetite of the SD group was significantly higher than that of the control group, but the body weight was significantly lower than that of the control group. The anxiety-like behaviors were found in the SD group. Alpha and beta diversity of microbiota showed significant decrease after ASD induction; the relative abundance of Candidatus_Arthromitus and Enterobacter was increased, whereas that abundance of Lactobacillus , Muribaculum , Monoglobus , Parasutterella , and others was decreased in the SD group. These effects were accompanied by reduction in fecal propionic acid. In the proximal colon, the SD group exhibited significantly higher inflammation (tumor necrosis factor-α [ TNF-α ]) and dysregulation of the circadian rhythms (brain and muscle ARNT-like 1 [ BMAL1 ] and cryptochrome circadian regulator 1 [ CRY1 ]) and tight junction genes (occludin [ OCLN ]) than the control group. Gut barrier dysfunction slightly increased the plasma concentration of lipopolysaccharide and significantly elevated TNF-α. Inflammatory signals might be transduced through the brain via TNF receptor superfamily member 1 A (TNFRSF1A), which significantly increased the levels of microglia activation marker (ionized calcium-binding adapter molecule 1 [ IBA1 ]) and chemokine (intercellular adhesion molecule 1 [ ICAM1 ]) in the cerebral cortex. The serotonin receptor (5-hydroxytryptamine 1A receptor [ 5-HT 1A R ]) was significantly downregulated in the hippocampus. In summary, 72 h of rapid eye movement-SD induced physiological and psychological stress, which led to disruption of the circadian rhythms and gut microbiota dysbiosis; these effects were related to decrement of short chain fatty acids, gut inflammation, and hyperpermeability. The microbiota may be utilized as preventive and therapeutic strategies for ASD from the perspectives of medicine and nutrition. [ABSTRACT FROM AUTHOR]