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Article ; Online: The dynamic balance of the skin microbiome across the lifespan.

Townsend, Elizabeth C / Kalan, Lindsay R

2023 Volume 51, Issue 1, Page(s) 71–86

Abstract: For decades research has centered on identifying the ideal balanced skin microbiome that prevents disease and on developing therapeutics to foster this balance. However, this single idealized balance may not exist. The skin microbiome changes across the ... ...

Abstract	For decades research has centered on identifying the ideal balanced skin microbiome that prevents disease and on developing therapeutics to foster this balance. However, this single idealized balance may not exist. The skin microbiome changes across the lifespan. This is reflected in the dynamic shifts of the skin microbiome's diverse, inter-connected community of microorganisms with age. While there are core skin microbial taxa, the precise community composition for any individual person is determined by local skin physiology, genetics, microbe-host interactions, and microbe-microbe interactions. As a key interface with the environment, the skin surface and its appendages are also constantly exchanging microbes with close personal contacts and the environment. Hormone fluctuations and immune system maturation also drive age-dependent changes in skin physiology that support different microbial community structures over time. Here, we review recent insights into the factors that shape the skin microbiome throughout life. Collectively, the works summarized within this review highlight how, depending on where we are in lifespan, our skin supports robust microbial communities, while still maintaining microbial features unique to us. This review will also highlight how disruptions to this dynamic microbial balance can influence risk for dermatological diseases as well as impact lifelong health.
MeSH term(s)	Humans ; Longevity ; Bacteria ; Microbiota ; Phylogeny ; Skin
Language	English
Publishing date	2023-01-05
Publishing country	England
Document type	Review ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	184237-7
ISSN	1470-8752 ; 0300-5127
ISSN (online)	1470-8752
ISSN	0300-5127
DOI	10.1042/BST20220216
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Article ; Online: What is slough? Defining the proteomic and microbial composition of slough and its implications for wound healing.

Townsend, Elizabeth C / Cheong, J Z Alex / Radzietza, Michael / Fritz, Blaine / Malone, Matthew / Bjarnsholt, Thomas / Ousey, Karen / Swanson, Terry / Schultz, Gregory / Gibson, Angela L F / Kalan, Lindsay R

Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society

2024

Abstract: Slough is a well-known feature of non-healing wounds. This pilot study aims to determine the proteomic and microbiologic components of slough as well as interrogate the associations between wound slough components and wound healing. Ten subjects with ... ...

Abstract	Slough is a well-known feature of non-healing wounds. This pilot study aims to determine the proteomic and microbiologic components of slough as well as interrogate the associations between wound slough components and wound healing. Ten subjects with slow-to-heal wounds and visible slough were enrolled. Aetiologies included venous stasis ulcers, post-surgical site infections and pressure ulcers. Patient co-morbidities and wound healing outcome at 3-months post-sample collection was recorded. Debrided slough was analysed microscopically, through untargeted proteomics, and high-throughput bacterial 16S-ribosomal gene sequencing. Microscopic imaging revealed wound slough to be amorphous in structure and highly variable. 16S-profiling found slough microbial communities to associate with wound aetiology and location on the body. Across all subjects, slough largely consisted of proteins involved in skin structure and formation, blood-clot formation and immune processes. To predict variables associated with wound healing, protein, microbial and clinical datasets were integrated into a supervised discriminant analysis. This analysis revealed that healing wounds were enriched for proteins involved in skin barrier development and negative regulation of immune responses. While wounds that deteriorated over time started off with a higher baseline Bates-Jensen Wound Assessment Score and were enriched for anaerobic bacterial taxa and chronic inflammatory proteins. To our knowledge, this is the first study to integrate clinical, microbiome, and proteomic data to systematically characterise wound slough and integrate it into a single assessment to predict wound healing outcome. Collectively, our findings underscore how slough components can help identify wounds at risk of continued impaired healing and serves as an underutilised biomarker.
Language	English
Publishing date	2024-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1174873-4
ISSN	1524-475X ; 1067-1927
ISSN (online)	1524-475X
ISSN	1067-1927
DOI	10.1111/wrr.13170
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Article ; Online: Key aspects of papillomavirus infection influence the host cervicovaginal microbiome in a preclinical murine papillomavirus (MmuPV1) infection model.

Spurgeon, Megan E / Townsend, Elizabeth C / Blaine-Sauer, Simon / McGregor, Stephanie M / Horswill, Mark / den Boon, Johan A / Ahlquist, Paul / Kalan, Lindsay / Lambert, Paul F

mBio

2024 , Page(s) e0093324

Abstract: Human papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States and are a major etiological agent of cancers in the anogenital tract and oral cavity. Growing evidence suggests changes in the host microbiome are ... ...

Abstract	Human papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States and are a major etiological agent of cancers in the anogenital tract and oral cavity. Growing evidence suggests changes in the host microbiome are associated with the natural history and ultimate outcome of HPV infection. We sought to define changes in the host cervicovaginal microbiome during papillomavirus infection, persistence, and pathogenesis using the murine papillomavirus (MmuPV1) cervicovaginal infection model. Cervicovaginal lavages were performed over a time course of MmuPV1 infection in immunocompetent female
Language	English
Publishing date	2024-05-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.00933-24
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Article: Discovery of a Novel Simian Pegivirus in Common Marmosets (Callithrix jacchus) with Lymphocytic Enterocolitis

Heffron, Anna S / Lauck, Michael / Somsen, Elizabeth D / Townsend, Elizabeth C / Bailey, Adam L / Sosa, Megan / Eickhoff, Jens / Capuano III, Saverio / Newman, Christina M / Kuhn, Jens H / Mejia, Andres / Simmons, Heather A / O’Connor, David H

Microorganisms. 2020 Sept. 30, v. 8, no. 10

2020

Abstract: From 2010 to 2015, 73 common marmosets (Callithrix jacchus) housed at the Wisconsin National Primate Research Center (WNPRC) were diagnosed postmortem with lymphocytic enterocolitis. We used unbiased deep-sequencing to screen the blood of deceased ... ...

Abstract	From 2010 to 2015, 73 common marmosets (Callithrix jacchus) housed at the Wisconsin National Primate Research Center (WNPRC) were diagnosed postmortem with lymphocytic enterocolitis. We used unbiased deep-sequencing to screen the blood of deceased enterocolitis-positive marmosets for viruses. In five out of eight common marmosets with lymphocytic enterocolitis, we discovered a novel pegivirus not present in ten matched, clinically normal controls. The novel virus, which we named Southwest bike trail virus (SOBV), is most closely related (68% nucleotide identity) to a strain of simian pegivirus A isolated from a three-striped night monkey (Aotus trivirgatus). We screened 146 living WNPRC common marmosets for SOBV, finding an overall prevalence of 34% (50/146). Over four years, 85 of these 146 animals died or were euthanized. Histological examination revealed 27 SOBV-positive marmosets from this cohort had lymphocytic enterocolitis, compared to 42 SOBV-negative marmosets, indicating no association between SOBV and disease in this cohort (p = 0.0798). We also detected SOBV in two of 33 (6%) clinically normal marmosets screened during transfer from the New England Primate Research Center, suggesting SOBV could be exerting confounding influences on comparisons of common marmoset studies from multiple colonies.
Keywords	Callithrix jacchus ; animals ; blood ; enterocolitis ; high-throughput nucleotide sequencing ; histology ; prevalence ; research ; viruses ; New England region ; Wisconsin
Language	English
Dates of publication	2020-0930
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-light
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms8101509
Database	NAL-Catalogue (AGRICOLA)

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Article: Discovery of a Novel Simian Pegivirus in Common Marmosets (

Heffron, Anna S / Lauck, Michael / Somsen, Elizabeth D / Townsend, Elizabeth C / Bailey, Adam L / Sosa, Megan / Eickhoff, Jens / Capuano Iii, Saverio / Newman, Christina M / Kuhn, Jens H / Mejia, Andres / Simmons, Heather A / O'Connor, David H

Microorganisms

2020 Volume 8, Issue 10

Abstract: From 2010 to 2015, 73 common marmosets ( ...

Abstract	From 2010 to 2015, 73 common marmosets (
Language	English
Publishing date	2020-09-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms8101509
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Article: Microbial Translocation in the Context of Hepatitis B Infection and Hepatitis D Infection.

Townsend, Elizabeth C / Zhang, Grace Y / Ali, Rabab / Surana, Pallavi / Firke, Marian / Moon, Mi Sun / Han, Ma Ai Thanda / Gewirtz, Meital / Haddad, James A / Kleiner, David E / Koh, Christopher / Heller, Theo

Open forum infectious diseases

2020 Volume 8, Issue 11, Page(s) ofaa496

Abstract: Background: Increased microbial translocation (MT) into the systemic circulation is associated with liver disease progression. Microbial translocation has yet to be completely defined in chronic hepatitis B virus (HBV) and chronic hepatitis delta virus ( ...

Abstract	Background: Increased microbial translocation (MT) into the systemic circulation is associated with liver disease progression. Microbial translocation has yet to be completely defined in chronic hepatitis B virus (HBV) and chronic hepatitis delta virus (HDV). Methods: Our aim was to characterize MT and associated immune response in chronic HBV and HDV at various stages of disease. Serum from 53 HBV, 43 HDV, and 36 healthy control (HC) subjects was obtained. Subjects were categorized by aspartate aminotransferase-to-platelet ratio index into mild (<0.5), moderate, and severe (>1.0) disease. Cytokines, microbial products, and microbial deoxyribonucleic acid (DNA) levels were assessed in a single treatment-naive time point for each patient. Next-generation sequencing identified bacterial species present within patient sera. Results: The HBV and HDV subjects display higher serum concentrations of Gram-negative (G Conclusions: The HBV and HDV patients display increased translocation of bacterial and fungal products into serum. An increased proportion of Gram-positive genera is associated with disease progression. Correlations of peptidoglycan with antimicrobial cytokines suggest that particular microbial classes may contribute to systemic inflammation and possibly disease progression.
Language	English
Publishing date	2020-10-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofaa496
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Article ; Online: Longitudinal multi-omics analyses of the gut-liver axis reveals metabolic dysregulation in hepatitis C infection and cirrhosis.

Nature microbiology

2022 Volume 8, Issue 1, Page(s) 12–27

Abstract: The gut and liver are connected via the portal vein, and this relationship, which includes the gut microbiome, is described as the gut-liver axis. Hepatitis C virus (HCV) can infect the liver and cause fibrosis with chronic infection. HCV has been ... ...

Abstract	The gut and liver are connected via the portal vein, and this relationship, which includes the gut microbiome, is described as the gut-liver axis. Hepatitis C virus (HCV) can infect the liver and cause fibrosis with chronic infection. HCV has been associated with an altered gut microbiome; however, how these changes impact metabolism across the gut-liver axis and how this varies with disease severity and time is unclear. Here we used multi-omics analysis of portal and peripheral blood, faeces and liver tissue to characterize the gut-liver axis of patients with HCV across a fibrosis severity gradient before (n = 29) and 6 months after (n = 23) sustained virologic response, that is, no detection of the virus. Fatty acids were the major metabolites perturbed across the liver, portal vein and gut microbiome in HCV, especially in patients with cirrhosis. Decreased fatty acid degradation by hepatic peroxisomes and mitochondria was coupled with increased free fatty acid (FFA) influx to the liver via the portal vein. Metatranscriptomics indicated that Anaerostipes hadrus-mediated fatty acid synthesis influences portal FFAs. Both microbial fatty acid synthesis and portal FFAs were associated with enhanced hepatic fibrosis. Bacteroides vulgatus-mediated intestinal glycan breakdown was linked to portal glycan products, which in turn correlated with enhanced portal inflammation in HCV. Paired comparison of patient samples at both timepoints showed that hepatic metabolism, especially in peroxisomes, is persistently dysregulated in cirrhosis independently of the virus. Sustained virologic response was associated with a potential beneficial role for Methanobrevibacter smithii, which correlated with liver disease severity markers. These results develop our understanding of the gut-liver axis in HCV and non-HCV liver disease aetiologies and provide a foundation for future therapies.
MeSH term(s)	Humans ; Multiomics ; Liver Cirrhosis ; Hepatitis C/complications ; Hepacivirus/genetics
Language	English
Publishing date	2022-12-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural
ISSN	2058-5276
ISSN (online)	2058-5276
DOI	10.1038/s41564-022-01273-y
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Article: Bacterial Translocation and Host Immune Activation in Chronic Hepatitis C Infection.

Moon, Mi Sun / Quinn, Gabriella / Townsend, Elizabeth C / Ali, Rabab O / Zhang, Grace Y / Bradshaw, Alyson / Hill, Kareen / Guan, Hannah / Hamilton, Destanee / Kleiner, David E / Koh, Christopher / Heller, Theo

Open forum infectious diseases

2019 Volume 6, Issue 7

Abstract: Hepatitis C virus (HCV) infects 71 million individuals, and barriers to treatment remain. Bacterial translocation is a complication of chronic HCV infection, and this study evaluated circulating microbial components including lipopolysaccharide, ... ...

Abstract	Hepatitis C virus (HCV) infects 71 million individuals, and barriers to treatment remain. Bacterial translocation is a complication of chronic HCV infection, and this study evaluated circulating microbial components including lipopolysaccharide, peptidoglycan, and β-D-glucan in addition to their pattern recognition receptors and degree of hepatic macrophage uptake. The findings suggest that regulation of serum peptidoglycan and β-D-glucan differs from that of lipopolysaccharide. Additionally, macrophage activation in the liver may be better reflected by the degree of macrophage uptake than by circulating levels of microbial markers. These findings allow for a greater understanding of bacterial translocation and host immune activation during HCV infection.
Language	English
Publishing date	2019-02-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofz255
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Article ; Online: The balance of type 1 and type 2 immune responses in the contexts of hepatitis B infection and hepatitis D infection.

Townsend, Elizabeth C / Zhang, Grace Y / Ali, Rabab / Firke, Marian / Moon, Mi Sun / Han, Ma Ai Thanda / Fram, Benjamin / Glenn, Jeffrey S / Kleiner, David E / Koh, Christopher / Heller, Theo

Journal of gastroenterology and hepatology

2019 Volume 34, Issue 4, Page(s) 764–775

Abstract: Background and aim: Hepatitis delta virus (HDV) infection is the most rapidly progressive chronic viral hepatitis. Little is understood about the immune responses to HDV. This study aims to characterize the systemic immune environments of hepatitis B ... ...

Abstract	Background and aim: Hepatitis delta virus (HDV) infection is the most rapidly progressive chronic viral hepatitis. Little is understood about the immune responses to HDV. This study aims to characterize the systemic immune environments of hepatitis B virus (HBV) and HDV patients at various disease stages. Methods: A total of 129 subjects were evaluated: 53 HBV, 43 HDV, and 33 healthy controls. HBV and HDV subjects were categorized by aspartate aminotransferase to platelet ratio index (APRI) into mild (APRI < 0.5), moderate, and severe (APRI > 1.0). Serum cytokines and immune markers were assessed at a single treatment-naïve time-point. Results: Type 1 cytokines are elevated in both HBV and HDV. Both groups show higher tumor necrosis factor-α (TNF-α), interleukin (IL)-12p40, and C-X-C motif chemokine ligand 9 when compared with controls (all P < 0.05). However, only HBV group displayed elevated γ-interferon compared with controls. Type 2 cytokines are elevated in HBV. HBV group shows higher IL-4, IL-13, and C-C motif chemokine ligand (CCL) 26 compared with healthy controls and HDV. Chemokines CCL2 and CCL13 are lower in HDV. When assessing ratios, HDV displays higher γ-interferon/IL-4, TNF-α/IL-4, and TNF-α/IL-13 ratios than HBV and controls. Conclusion: Hepatitis B virus and HDV subjects show similarly elevated type 1 cytokines. HDV subjects display relatively lower type 2 cytokines. These differences in the systemic immune environments, particularly the predominance of type 1 responses, may contribute to the comparatively rapid progression of HDV disease. Characterization of the imbalance in type 1 and type 2 immunity unique HDV has the potential to provide immunological insights for designing therapeutic targets in HDV-associated disease progression.
MeSH term(s)	Adult ; Aged ; Chemokine CCL2/blood ; Chemokines, CXC/blood ; Cytokines/blood ; Disease Progression ; Female ; Hepatitis B/immunology ; Hepatitis B virus/immunology ; Hepatitis D/immunology ; Hepatitis D/therapy ; Hepatitis Delta Virus/immunology ; Humans ; Interferon-gamma/blood ; Interleukin-12/blood ; Interleukin-13/blood ; Interleukin-4/blood ; Male ; Middle Aged ; Molecular Targeted Therapy ; Tumor Necrosis Factor-alpha/blood
Chemical Substances	Chemokine CCL2 ; Chemokines, CXC ; Cytokines ; Interleukin-13 ; Tumor Necrosis Factor-alpha ; Interleukin-12 (187348-17-0) ; Interleukin-4 (207137-56-2) ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2019-02-25
Publishing country	Australia
Document type	Journal Article
ZDB-ID	632882-9
ISSN	1440-1746 ; 0815-9319
ISSN (online)	1440-1746
ISSN	0815-9319
DOI	10.1111/jgh.14617
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Zs.A 2180: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Exploring the Link Between Platelet Numbers and Vascular Homeostasis Across Early and Late Stages of Fibrosis in Hepatitis C.

Ali, Rabab O / Moon, Mi Sun / Townsend, Elizabeth C / Hill, Kareen / Zhang, Grace Y / Bradshaw, Alyson / Guan, Hannah / Hamilton, Destanee / Kleiner, David E / Auh, Sungyoung / Koh, Christopher / Heller, Theo

Digestive diseases and sciences

2019 Volume 65, Issue 2, Page(s) 524–533

Abstract: Background: Thrombocytopenia is a hallmark of advanced liver disease. Platelets, growth factors (GFs), and vascular integrity are closely linked factors in disease pathogenesis, and their relationship, particularly in early disease stages, is not ... ...

Abstract	Background: Thrombocytopenia is a hallmark of advanced liver disease. Platelets, growth factors (GFs), and vascular integrity are closely linked factors in disease pathogenesis, and their relationship, particularly in early disease stages, is not entirely understood. The aim was to compare circulating platelets, growth factors, and vascular injury markers (VIMs) in hepatitis C-infected (HCV) patients with early fibrosis and cirrhosis. Methods: Retrospective evaluation of serum GFs and VIMs by ELISA were evaluated from twenty-six HCV patients. Analytes from an earlier time-point were correlated with MELD at a later time-point. Results: Platelets and GFs decreased, and VIMs increased with fibrosis. Platelets correlated positively with PDGF-AA, PDGF-BB, TGFB1, EGF, and P-selectin, and negatively with ICAM-3 and VCAM-1. P-selectin showed no correlations with VIMs but positively correlated with PDGF-AA, PDGF-BB, TGFB1, and EGF. Soluble VCAM-1 and ICAM-3 were linked to increasing fibrosis, liver enzymes, and synthetic dysfunction. Higher VCAM-1 and ICAM-3 and lower P-selectin at an earlier time-point were linked to higher MELD score at a later time-point. Conclusion: In chronic HCV, progressive decline in platelets and growth factors with fibrosis and their associations suggest that platelets are an important source of circulating GFs and influence GF decline with fibrosis. Enhanced markers of vascular injury in patients with early fibrosis suggest an earlier onset of endothelial dysfunction preceding cirrhosis. Associations of VIMs with platelets suggest a critical link between platelets and vascular homeostasis. Circulating markers of vascular injury may not only have prognostic importance but emphasize the role of vascular dysfunction in liver disease pathogenesis (NCT00001971).
MeSH term(s)	Adult ; Antigens, CD/blood ; Becaplermin/blood ; Biomarkers ; Cell Adhesion Molecules/blood ; Disease Progression ; End Stage Liver Disease/blood ; End Stage Liver Disease/metabolism ; Endothelial Growth Factors/blood ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/physiopathology ; Enzyme-Linked Immunosorbent Assay ; Female ; Hepatitis C, Chronic/blood ; Hepatitis C, Chronic/complications ; Hepatitis C, Chronic/metabolism ; Homeostasis ; Humans ; Liver Cirrhosis/blood ; Liver Cirrhosis/etiology ; Longitudinal Studies ; Male ; Middle Aged ; P-Selectin/blood ; Platelet Count ; Platelet-Derived Growth Factor/metabolism ; Retrospective Studies ; Severity of Illness Index ; Thrombocytopenia/blood ; Thrombocytopenia/etiology ; Thrombocytopenia/metabolism ; Transforming Growth Factor beta1/blood ; Vascular Cell Adhesion Molecule-1/blood
Chemical Substances	Antigens, CD ; Biomarkers ; Cell Adhesion Molecules ; Endothelial Growth Factors ; ICAM3 protein, human ; P-Selectin ; Platelet-Derived Growth Factor ; TGFB1 protein, human ; Transforming Growth Factor beta1 ; Vascular Cell Adhesion Molecule-1 ; platelet-derived growth factor A ; Becaplermin (1B56C968OA)
Language	English
Publishing date	2019-08-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	304250-9
ISSN	1573-2568 ; 0163-2116
ISSN (online)	1573-2568
ISSN	0163-2116
DOI	10.1007/s10620-019-05760-x
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