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Title: Gut mycobiome dysbiosis after sepsis and trauma
AbstractBackground
Sepsis and trauma are known to disrupt gut bacterial microbiome communities, but the impacts and perturbations in the fungal (mycobiome) community after severe infection or injury, particularly in patients experiencing chronic critical illness (CCI), remain unstudied.
Methods
We assess persistence of the gut mycobiome perturbation (dysbiosis) in patients experiencing CCI following sepsis or trauma for up to two-to-three weeks after intensive care unit hospitalization.
Results
We show that the dysbiotic mycobiome arrays shift toward a pathobiome state, which is more susceptible to infection, in CCI patients compared to age-matched healthy subjects. The fungal community in CCI patients is largely dominated byCandidaspp; while, the commensal fungal species are depleted. Additionally, these myco-pathobiome arrays correlate with alterations in micro-ecological niche involving specific gut bacteria and gut-blood metabolites.
Conclusions
The findings reveal the persistence of mycobiome dysbiosis in both sepsis and trauma settings, even up to two weeks post-sepsis and trauma, highlighting the need to assess and address the increased risk of fungal infections in CCI patients.
Environmentally friendly insect management technologies, including RNA interference (RNAi) and entomopathogenic fungi, have attracted increasing attention as options for pest control. Here, we sought to extend RNAi‐directed targeting of the inhibitor of apoptosis protein 1 (IAP1) gene to the locust, and to examine its relationship to immune responses and susceptibility toMetarhizium acridum, a locust‐specific fungal pathogen.
RESULTS
Expression of the locustLmIAPgene was induced in the hemolymph and fat body afterM. acriduminfection. RNAi‐directed silencing of locustLmIAP1resulted in increased caspase3activity, degeneration of the gut and dose‐dependent mortality. Synergistic mortality was seen in RNAi‐LmIAP/fungal co‐infection experiments with median survival time (MST) values decreasing from ∼ 5 days for RNAi andM. acridumtreatments alone, to 2.6 days for co‐treatments. Reduced hemocyte numbers and antimicrobial peptide levels were seen in co‐treated locusts, with changes in gut opportunistic pathogenic bacteria seen between treatments. Enhanced fungal sporulation on co‐treated insect cadavers was also compared with fungal infection alone.
Tawfik, Vivianne L.; Quarta, Marco; Paine, Patrick; Forman, Thomas E.; Pajarinen, Jukka; Takemura, Yoshinori; Goodman, Stuart B.; Rando, Thomas A.; Clark, J. David(
, The Journal of Physiology)
Key points
Our tibial fracture orthopaedic injury model in mice recapitulates the major manifestations of complex trauma, including nociceptive sensitization, bone fracture, muscle fibrosis and muscle fibre loss.
Delayed exercise after complex orthopaedic trauma results in decreased muscle fibrosis and improved pain
Losartan, an angiotensin‐receptor blocker with anti‐fibrotic abilities, recapitulates the effect of exercise on post‐injury recovery and may provide an enhanced recovery option for those who are unable to exercise after injury
Abstract
Chronic pain and disability after limb injury are major public health problems. Early mobilization after injury improves functional outcomes for patients, although when and how to implement rehabilitation strategies remains a clinical challenge. Additionally, whether the beneficial effects of exercise can be reproduced using pharmacological tools remains unknown and may benefit patients who are unable to exercise as a result of immobilization. We developed a murine model of orthopaedic trauma combining tibia fracture and pin fixation with muscle damage. Behavioural measures included mechanical nociceptive thresholds and distances run on exercise wheels. Bone healing was quantified using microcomputed tomagraphic scanning, and muscle fibre size distribution and fibrosis were followed using immunohistochemistry. We found that the model provided robust mechanical allodynia, fibrosis and a shift to smaller average muscle fibre size lasting up to 5 weeks from injury. We also observed that allowing ‘late’ (weeks 1–2) rather than ‘early’ (weeks 0–1) exercise after injury resulted in greater overall running activity and greater reversal of allodynia. In parallel, the late running paradigm was associated with reduced muscle fibrosis, earlier increase in muscle fibre diameter and a short‐term benefit in reducing callus volume. Providing the anti‐fibrotic angiotensin receptor blocker losartan to mice in drinking water reduced both allodynia and muscle fibrosis. Combining losartan and late exercise provided no additional benefit. We conclude that early healing after orthopaedic trauma must be allowed prior to the initiation of exercise to achieve optimal pain, functional and physiological outcomes and that losartan is a viable candidate for translational studies.
Guittar, John; Koffel, Thomas; Shade, Ashley; Klausmeier, Christopher A; Litchman, Elena(
, The American Naturalist)
null
(Ed.)
The spread of an enteric pathogen in the human gut depends on many interacting factors, including pathogen exposure, diet, host gut environment, and host microbiota, but how these factors jointly influence infection outcomes remains poorly characterized. Here, we develop a model of host-mediated resource-competition between mutualistic and pathogenic taxa in the gut that aims to explain why similar hosts, exposed to the same pathogen, can have such different infection outcomes. Our model successfully reproduces several empirically observed phenomena related to transitions between healthy and infected states, including (1) the nonlinear relationship between pathogen inoculum size and infection persistence, (2) the elevated risk of chronic infection during or after treatment with broad-spectrum antibiotics, (3) the resolution of gut dysbiosis with fecal microbiota transplants, and (4) the potential protection from infection conferred by probiotics. We then use the model to explore how host-mediated interventions, namely shifts in the supply rates of electron donors (e.g., dietary fiber) and respiratory electron acceptors (e.g., oxygen), can potentially be used to direct gut community assembly. Our study demonstrates how resource competition and ecological feedbacks between the host and the gut microbiota can be critical determinants of human health outcomes. We identify several testable model predictions ready for experimental validation.
Buendia, Patricia; Fernandez, Krystal; Raley, Castle; Rahnavard, Ali; Crandall, Keith A; Castro, Jose Guillermo(
, Frontiers in Microbiology)
Introduction
During the COVID-19 Delta variant surge, the CLAIRE cross-sectional study sampled saliva from 120 hospitalized patients, 116 of whom had a positive COVID-19 PCR test. Patients received antibiotics upon admission due to possible secondary bacterial infections, with patients at risk of sepsis receiving broad-spectrum antibiotics (BSA).
Methods
The saliva samples were analyzed with shotgun DNA metagenomics and respiratory RNA virome sequencing. Medical records for the period of hospitalization were obtained for all patients. Once hospitalization outcomes were known, patients were classified based on their COVID-19 disease severity and the antibiotics they received.
Results
Our study reveals that BSA regimens differentially impacted the human salivary microbiome and disease progression. 12 patients died and all of them received BSA. Significant associations were found between the composition of the COVID-19 saliva microbiome and BSA use, between SARS-CoV-2 genome coverage and severity of disease. We also found significant associations between the non-bacterial microbiome and severity of disease, withCandida albicansdetected most frequently in critical patients. For patients who did not receive BSA before saliva sampling, our study suggestsStaphylococcus aureusas a potential risk factor for sepsis.
Discussion
Our results indicate that the course of the infection may be explained by both monitoring antibiotic treatment and profiling a patient’s salivary microbiome, establishing a compelling link between microbiome and the specific antibiotic type and timing of treatment. This approach can aid with emergency room triage and inpatient management but also requires a better understanding of and access to narrow-spectrum agents that target pathogenic bacteria.
Meili, Casey H; TagElDein, Moustafa A; Jones, Adrienne L; Moon, Christina D; Andrews, Catherine; Kirk, Michelle R; Janssen, Peter H; J_Yeoman, Carl; Grace, Savannah; Borgogna, Joanna-Lynn C; et al(
, Applied and Environmental Microbiology)
Reguera, Gemma
(Ed.)
ABSTRACT
The rumen houses a diverse community that plays a major role in the digestion process in ruminants. Anaerobic gut fungi (AGF) are key contributors to plant digestion in the rumen. Here, we present a global amplicon-based survey of the rumen AGF mycobiome by examining 206 samples from 15 animal species, 15 countries, and 6 continents. The rumen AGF mycobiome was highly diverse, with 81 out of 88 currently recognized AGF genera or candidate genera identified. However, only six genera (Neocallimastix, Orpinomyces, Caecomyces, Cyllamyces,NY9, andPiromyces) were present at >4% relative abundance. AGF diversity was higher in members of the familiesAntilocapridaeandCervidaecompared toBovidae. Community structure analysis identified a pattern of phylosymbiosis, where host family (10% of total variance) and species (13.5%) partially explained the rumen mycobiome composition. As well, diet composition (9%–19%), domestication (11.14%), and biogeography (14.1%) also partially explained AGF community structure; although sampling limitation, geographic range restrictions, and direct association between different factors hindered accurate elucidation of the relative contribution of each factor. Pairwise comparison of rumen and fecal samples obtained from the same subject (n= 13) demonstrated greater diversity and inter-sample variability in rumen versus fecal samples. The generaNeocallimastixandOrpinomyceswere present in higher abundance in rumen samples, whileCyllamycesandCaecomyceswere enriched in fecal samples. Comparative analysis of global rumen and feces data sets revealed a similar pattern. Our results provide a global view of AGF community in the rumen and identify patterns of AGF variability between rumen and feces in herbivores Gastrointestinal (GI) tract.
IMPORTANCE
Ruminants are highly successful and economically important mammalian suborder. Ruminants are herbivores that digest plant material with the aid of microorganisms residing in their GI tract. In ruminants, the rumen compartment represents the most important location where microbially mediated plant digestion occurs, and is known to house a bewildering array of microbial diversity. An important component of the rumen microbiome is the anaerobic gut fungi (AGF), members of the phylumNeocallimastigomycota. So far, studies examining AGF diversity have mostly employed fecal samples, and little is currently known regarding the identity of AGF residing in the rumen compartment, factors that impact the observed patterns of diversity and community structure of AGF in the rumen, and how AGF communities in the rumen compare to AGF communities in feces. Here, we examined the rumen AGF diversity using an amplicon-based survey targeting a wide range of wild and domesticated ruminants (n= 206, 15 different animal species) obtained from 15 different countries. Our results demonstrate that while highly diverse, no new AGF genera were identified in the rumen mycobiome samples examined. Our analysis also indicate that animal host phylogeny, diet, biogeography, and domestication status could play a role in shaping AGF community structure. Finally, we demonstrate that a greater level of diversity and higher inter-sample variability was observed in rumen compared to fecal samples, with two genera (NeocallimastixandOrpinomyces) present in higher abundance in rumen samples, and two others (CyllamycesandCaecomyces) enriched in fecal samples. Our results provide a global view of the identity, diversity, and community structure of AGF in ruminants, elucidate factors impacting diversity and community structure of the rumen mycobiome, and identify patterns of AGF community variability between the rumen and feces in the herbivorous GI tract.
Park, Gwoncheol, Munley, Jennifer A, Kelly, Lauren S, Kannan, Kolenkode B, Mankowski, Robert T, Sharma, Ashish, Upchurch, Gilbert, Casadesus, Gemma, Chakrabarty, Paramita, Wallet, Shannon M, Maile, Robert, Bible, Letitia E, Wang, Bo, Moldawer, Lyle L, Mohr, Alicia M, Efron, Philip A, and Nagpal, Ravinder. Gut mycobiome dysbiosis after sepsis and trauma. Retrieved from https://par.nsf.gov/biblio/10533345. Critical Care 28.1 Web. doi:10.1186/s13054-023-04780-4.
Park, Gwoncheol, Munley, Jennifer A, Kelly, Lauren S, Kannan, Kolenkode B, Mankowski, Robert T, Sharma, Ashish, Upchurch, Gilbert, Casadesus, Gemma, Chakrabarty, Paramita, Wallet, Shannon M, Maile, Robert, Bible, Letitia E, Wang, Bo, Moldawer, Lyle L, Mohr, Alicia M, Efron, Philip A, & Nagpal, Ravinder. Gut mycobiome dysbiosis after sepsis and trauma. Critical Care, 28 (1). Retrieved from https://par.nsf.gov/biblio/10533345. https://doi.org/10.1186/s13054-023-04780-4
Park, Gwoncheol, Munley, Jennifer A, Kelly, Lauren S, Kannan, Kolenkode B, Mankowski, Robert T, Sharma, Ashish, Upchurch, Gilbert, Casadesus, Gemma, Chakrabarty, Paramita, Wallet, Shannon M, Maile, Robert, Bible, Letitia E, Wang, Bo, Moldawer, Lyle L, Mohr, Alicia M, Efron, Philip A, and Nagpal, Ravinder.
"Gut mycobiome dysbiosis after sepsis and trauma". Critical Care 28 (1). Country unknown/Code not available: Critical Care. https://doi.org/10.1186/s13054-023-04780-4.https://par.nsf.gov/biblio/10533345.
@article{osti_10533345,
place = {Country unknown/Code not available},
title = {Gut mycobiome dysbiosis after sepsis and trauma},
url = {https://par.nsf.gov/biblio/10533345},
DOI = {10.1186/s13054-023-04780-4},
abstractNote = {Abstract BackgroundSepsis and trauma are known to disrupt gut bacterial microbiome communities, but the impacts and perturbations in the fungal (mycobiome) community after severe infection or injury, particularly in patients experiencing chronic critical illness (CCI), remain unstudied. MethodsWe assess persistence of the gut mycobiome perturbation (dysbiosis) in patients experiencing CCI following sepsis or trauma for up to two-to-three weeks after intensive care unit hospitalization. ResultsWe show that the dysbiotic mycobiome arrays shift toward a pathobiome state, which is more susceptible to infection, in CCI patients compared to age-matched healthy subjects. The fungal community in CCI patients is largely dominated byCandidaspp; while, the commensal fungal species are depleted. Additionally, these myco-pathobiome arrays correlate with alterations in micro-ecological niche involving specific gut bacteria and gut-blood metabolites. ConclusionsThe findings reveal the persistence of mycobiome dysbiosis in both sepsis and trauma settings, even up to two weeks post-sepsis and trauma, highlighting the need to assess and address the increased risk of fungal infections in CCI patients. Graphical Abstract},
journal = {Critical Care},
volume = {28},
number = {1},
publisher = {Critical Care},
author = {Park, Gwoncheol and Munley, Jennifer A and Kelly, Lauren S and Kannan, Kolenkode B and Mankowski, Robert T and Sharma, Ashish and Upchurch, Gilbert and Casadesus, Gemma and Chakrabarty, Paramita and Wallet, Shannon M and Maile, Robert and Bible, Letitia E and Wang, Bo and Moldawer, Lyle L and Mohr, Alicia M and Efron, Philip A and Nagpal, Ravinder},
}
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