Erratum: Corrigendum: Gut microbiome–derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease

Mathewson, Nathan D.; Jenq, Robert R.; Mathew, Anna V.; Koenigsknecht, Mark J.; Hanash, Alan M.; Toubai, Tomomi; Oravecz-Wilson, Katherine; Wu, S. Julia; Sun, Yaping; Rossi, Corinne; Fujiwara, Hideaki; Byun, Jaeman; Shono, Yusuke; Lindemans, Caroline A.; Calafiore, Marco; Schmidt, Thomas C.; Honda, Kenya; Young, Vincent B.; Pennathur, Subramaniam; Brink, Marcel van den; Reddy, Pavan

doi:10.1038/ni1016-1235b

Cited by 20 publications

(11 citation statements)

References 1 publication

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“…Efforts to maintain the mucosal barrier and host microbiota are therefore warranted and may aid in reducing the over-reliance on antimicrobials. This is particularly relevant in the broader setting of HSCT, in which antibiotic-induced disruption of the microbiota has been shown to exacerbate graft-versus-host disease (GvHD) and increase mortality [12,43].…”

Section: Discussionmentioning

confidence: 99%

Translational model of melphalan-induced gut toxicity reveals drug-host-microbe interactions that drive tissue injury and fever

Wardill

Mooij

Ferreira

et al. 2021

Cancer Chemother Pharmacol

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Purpose Conditioning therapy with high-dose melphalan (HDM) is associated with a high risk of gut toxicity, fever and infections in haematopoietic stem cell transplant (HSCT) recipients. However, validated preclinical models that adequately reflect clinical features of melphalan-induced toxicity are not available. We therefore aimed to develop a novel preclinical model of melphalan-induced toxicity that reflected well-defined clinical dynamics, as well as to identify targetable mechanisms that drive intestinal injury. Methods Male Wistar rats were treated with 4–8 mg/kg melphalan intravenously. The primary endpoint was plasma citrulline. Secondary endpoints included survival, weight loss, diarrhea, food/water intake, histopathology, body temperature, microbiota composition (16S sequencing) and bacterial translocation. Results Melphalan 5 mg/kg caused self-limiting intestinal injury, severe neutropenia and fever while impairing the microbial metabolome, prompting expansion of enteric pathogens. Intestinal inflammation was characterized by infiltration of polymorphic nuclear cells in the acute phases of mucosal injury, driving derangement of intestinal architecture. Ileal atrophy prevented bile acid reabsorption, exacerbating colonic injury via microbiota-dependent mechanisms. Conclusion We developed a novel translational model of melphalan-induced toxicity, which has excellent homology with the well-known clinical features of HDM transplantation. Application of this model will accelerate fundamental and translational study of melphalan-induced toxicity, with the clinical parallels of this model ensuring a greater likelihood of clinical success. Graphic abstract

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Section: Discussionmentioning

confidence: 99%

Translational model of melphalan-induced gut toxicity reveals drug-host-microbe interactions that drive tissue injury and fever

Wardill

Mooij

Ferreira

et al. 2021

Cancer Chemother Pharmacol

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“…71 The importance of the gut microbiome is increasingly recognized as connections have been found between the microbiome and autism, mental disorders, transplant integration, obesity, allergies, and cancer. [72][73][74][75][76][77] In summary, intestinal homeostasis is a complex phenomenon that depends on many factors: intercellular signaling within the epithelium, paracrine communication between the epithelium and mesenchyme, mechanical stimuli, and ECM cues. Moreover, it is incredibly important in both intestinal physiology and pathology.…”

Section: Gut Microbiomementioning

confidence: 99%

In VitroModels of the Small Intestine: Engineering Challenges and Engineering Solutions

Hewes

Wilson

Estes

et al. 2020

Tissue Engineering Part B: Reviews

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Pathologies affecting the small intestine contribute significantly to the disease burden of both the developing and the developed world, which has motivated investigation into the disease mechanisms through in vitro models. Although existing in vitro models recapitulate selected features of the intestine, various important aspects have often been isolated or omitted due to the anatomical and physiological complexity. The small intestine's intricate microanatomy, heterogeneous cell populations, steep oxygen gradients, microbiota, and intestinal wall contractions are often not included in in vitro experimental models of the small intestine, despite their importance in both intestinal biology and pathology. Known and unknown interdependencies between various physiological aspects necessitate more complex in vitro models. Microfluidic technology has made it possible to mimic the dynamic mechanical environment, signaling gradients, and other important aspects of small intestinal biology. This review presents an overview of the complexity of small intestinal anatomy and bioengineered models that recapitulate some of these physiological aspects. Keywords: gut-on-a-chip, microfluidic models of intestine, small intestine model, tissue engineered intestine Impact Statement There is a need for improved cell culture models of the small intestine. To develop such models, it is necessary to give engineers a better understanding of intestinal biology, and conversely, to give biologists an idea of what is possible with microfluidic devices and biomaterial platforms. This work provides a detailed overview of aspects of intestinal biology that are important for tissue engineers to understand when designing models of the small intestine and provides a summary of current approaches. This review highlights both unique and common features of various strategies for modeling the intestinal cell environment, not only using microfluidic chip-based systems but also several elegant designs that use a materials-based static culture approach.

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“…Ggtree was next used for dendrogram construction 72 . ReactomePA package was used for functional GSEA 73 . All unique detected genes in the cell subset were sorted by log fold change values to create ranked list that was inputted for GSEA analysis.…”

Section: Downstream Analysismentioning

confidence: 99%

Metabolic dysregulation induces impaired lymphocyte memory formation during severe SARS-CoV-2 infection

Nguyen

Gurshaney

Alvarez

et al. 2021

Preprint

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Cellular metabolic dysregulation is a consequence of COVID-19 infection that is a key determinant of disease severity. To understand the mechanisms underlying these cellular changes, we performed high-dimensional immune cell profiling of PBMCs from COVID-19-infected patients, in combination with single cell transcriptomic analysis of COVID-19 BALFs. Hypoxia, a hallmark of COVID-19 ARDS, was found to elicit a global metabolic reprogramming in effector lymphocytes. In response to oxygen and nutrient-deprived microenvironments, these cells shift from aerobic respiration to increase their dependence on anaerobic processes including glycolysis, mitophagy, and glutaminolysis to fulfill their bioenergetic demands. We also demonstrate metabolic dysregulation of ciliated lung epithelial cells is linked to significant increase of proinflammatory cytokine secretion and upregulation of HLA class 1 machinery. Augmented HLA class-1 antigen stimulation by epithelial cells leads to cellular exhaustion of metabolically dysregulated CD8 and NK cells, impairing their memory cell differentiation. Unsupervised clustering techniques revealed multiple distinct, differentially abundant CD8 and NK memory cell states that are marked by high glycolytic flux, mitochondrial dysfunction, and cellular exhaustion, further highlighting the connection between disrupted metabolism and impaired memory cell function in COVID-19. Our findings provide novel insight on how SARS-CoV-2 infection affects host immunometabolism and anti-viral response during COVID-19.

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Erratum: Corrigendum: Gut microbiome–derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease

Cited by 20 publications

References 1 publication

Translational model of melphalan-induced gut toxicity reveals drug-host-microbe interactions that drive tissue injury and fever

Translational model of melphalan-induced gut toxicity reveals drug-host-microbe interactions that drive tissue injury and fever

In VitroModels of the Small Intestine: Engineering Challenges and Engineering Solutions

Metabolic dysregulation induces impaired lymphocyte memory formation during severe SARS-CoV-2 infection

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