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21 pages, 3902 KiB

Open AccessArticle

Neutrophil Extracellular Traps in Severe SARS-CoV-2 Infection: A Possible Impact of LPS and (1→3)-β-D-glucan in Blood from Gut Translocation

by Supichcha Saithong, Navaporn Worasilchai, Wilasinee Saisorn, Kanyarat Udompornpitak, Thansita Bhunyakarnjanarat, Ariya Chindamporn, Punyot Tovichayathamrong, Pattama Torvorapanit, Direkrit Chiewchengchol, Wiwat Chancharoenthana and Asada Leelahavanichkul

Cells 2022, 11(7), 1103; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11071103 - 24 Mar 2022

Cited by 16 | Viewed by 3179

Abstract

Due to limited data on the link between gut barrier defects (leaky gut) and neutrophil extracellular traps (NETs) in coronavirus disease 2019 (COVID-19), blood samples of COVID-19 cases—mild (upper respiratory tract symptoms without pneumonia; n = 27), moderate (pneumonia without hypoxia; n = [...] Read more.

Due to limited data on the link between gut barrier defects (leaky gut) and neutrophil extracellular traps (NETs) in coronavirus disease 2019 (COVID-19), blood samples of COVID-19 cases—mild (upper respiratory tract symptoms without pneumonia; n = 27), moderate (pneumonia without hypoxia; n = 28), and severe (pneumonia with hypoxia; n = 20)—versus healthy control (n = 15) were evaluated, together with in vitro experiments. Accordingly, neutrophil counts, serum cytokines (IL-6 and IL-8), lipopolysaccharide (LPS), bacteria-free DNA, and NETs parameters (fluorescent-stained nuclear morphology, dsDNA, neutrophil elastase, histone–DNA complex, and myeloperoxidase–DNA complex) were found to differentiate COVID-19 severity, whereas serum (1→3)-β-D-glucan (BG) was different between the control and COVID-19 cases. Despite non-detectable bacteria-free DNA in the blood of healthy volunteers, using blood bacteriome analysis, proteobacterial DNA was similarly predominant in both control and COVID-19 cases (all severities). In parallel, only COVID-19 samples from moderate and severe cases, but not mild cases, were activated in vitro NETs, as determined by supernatant dsDNA, Peptidyl Arginine Deiminase 4, and nuclear morphology. With neutrophil experiments, LPS plus BG (LPS + BG) more prominently induced NETs, cytokines, NFκB, and reactive oxygen species, when compared with the activation by each molecule alone. In conclusion, pathogen molecules (LPS and BG) from gut translocation along with neutrophilia and cytokinemia in COVID-19-activated, NETs-induced hyperinflammation. Full article

(This article belongs to the Special Issue Microbiota, Inflammation and Systemic Diseases)

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16 pages, 2361 KiB

Open AccessArticle

Microbiome Analysis of Mucosal Ileoanal Pouch in Ulcerative Colitis Patients Revealed Impairment of the Pouches Immunometabolites

by Orazio Palmieri, Stefano Castellana, Giuseppe Biscaglia, Anna Panza, Anna Latiano, Rosanna Fontana, Maria Guerra, Giuseppe Corritore, Tiziana Latiano, Giuseppina Martino, Tommaso Mazza, Angelo Andriulli, Francesco Perri and Fabrizio Bossa

Cells 2021, 10(11), 3243; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10113243 - 19 Nov 2021

Cited by 8 | Viewed by 3474

Abstract

The pathogenesis of ulcerative colitis (UC) is unknown, although genetic loci and altered gut microbiota have been implicated. Up to a third of patients with moderate to severe UC require proctocolectomy with ileal pouch ano-anastomosis (IPAA). We aimed to explore the mucosal microbiota [...] Read more.

The pathogenesis of ulcerative colitis (UC) is unknown, although genetic loci and altered gut microbiota have been implicated. Up to a third of patients with moderate to severe UC require proctocolectomy with ileal pouch ano-anastomosis (IPAA). We aimed to explore the mucosal microbiota of UC patients who underwent IPAA. Methods: For microbiome analysis, mucosal specimens were collected from 34 IPAA individuals. Endoscopic and histological examinations of IPAA were normal in 21 cases, while pouchitis was in 13 patients. 19 specimens from the healthy control (10 from colonic and 9 from ileum) were also analyzed. Data were analyzed using an ensemble of software packages: QIIME2, coda-lasso, clr-lasso, PICRUSt2, and ALDEx2. Results: IPAA specimens had significantly lower bacterial diversity as compared to normal. The microbial composition of the normal pouch was also decreased also when compared to pouchitis. Faecalibacterium prausnitzii, Gemmiger formicilis, Blautia obeum, Ruminococcus torques, Dorea formicigenerans, and an unknown species from Roseburia were the most uncommon in pouch/pouchitis, while an unknown species from Enterobacteriaceae was over-represented. Propionibacterium acnes and Enterobacteriaceae were the species most abundant in the pouchitis and in the normal pouch, respectively. Predicted metabolic pathways among the IPAA bacterial communities revealed an important role of immunometabolites such as SCFA, butyrate, and amino acids. Conclusions: Our findings showed specific bacterial signature hallmarks of dysbiosis and could represent bacterial biomarkers in IPAA patients useful to develop novel treatments in the future by modulating the gut microbiota through the administration of probiotic immunometabolites-producing bacterial strains and the addition of specific prebiotics and the faecal microbiota transplantation. Full article

(This article belongs to the Special Issue Microbiota, Inflammation and Systemic Diseases)

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13 pages, 2880 KiB

Open AccessCommunication

A Microbiome-Derived Peptide Induces Apoptosis of Cells from Different Tissues

by Haruko Saiki, Yuko Okano, Taro Yasuma, Masaaki Toda, Atsuro Takeshita, Ahmed M. Abdel-Hamid, Valeria Fridman D’Alessandro, Tatsuki Tsuruga, Corina N. D’Alessandro-Gabazza, Kan Katayama, Masahiko Sugimoto, Hajime Fujimoto, Keiichi Yamanaka, Tetsu Kobayashi, Isaac Cann and Esteban C. Gabazza

Cells 2021, 10(11), 2885; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10112885 - 26 Oct 2021

Cited by 8 | Viewed by 2015

Abstract

Apoptosis is a programmed cell death involved in embryogenesis and tissue homeostasis under physiological conditions. However, abnormalities in the process of apoptosis are implicated in the pathogenesis of various diseases. The human microbiota may release products that induce apoptosis of host cells. We [...] Read more.

Apoptosis is a programmed cell death involved in embryogenesis and tissue homeostasis under physiological conditions. However, abnormalities in the process of apoptosis are implicated in the pathogenesis of various diseases. The human microbiota may release products that induce apoptosis of host cells. We recently identified a novel microbiome-derived peptide called corisin that worsens lung fibrosis by inducing apoptosis of lung epithelial cells. We hypothesized that corisin and a corisin-like peptide might also induce apoptosis of cells from different tissues. We cultured podocytes, renal tubular epithelial cells, keratinocytes, retinal and intestinal cells treated with corisin and evaluated apoptosis by flow cytometry and Western blotting. Although at different grades, flow cytometry analysis and Western blotting showed that corisin and a corisin-like peptide induced apoptosis of podocytes, keratinocytes, tubular epithelial cells, retinal, and intestinal cells. In addition, we found that corisin synergistically enhances the proapoptotic activity of transforming growth factor-β1 on podocytes. In conclusion, these results suggest that corisin and corisin-like peptides may play a role in the pathogenesis of disease in different organs by promoting apoptosis of parenchymal cells. Full article

(This article belongs to the Special Issue Microbiota, Inflammation and Systemic Diseases)

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16 pages, 5697 KiB

Open AccessArticle

Compositional Features of Distinct Microbiota Base on Serum Extracellular Vesicle Metagenomics Analysis in Moderate to Severe Psoriasis Patients

by Chih-Jung Chang, Jing Zhang, Yu-Ling Tsai, Chun-Bing Chen, Chun-Wei Lu, Yu-Ping Huo, Huey-Ming Liou, Chao Ji and Wen-Hung Chung

Cells 2021, 10(9), 2349; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10092349 - 08 Sep 2021

Cited by 10 | Viewed by 3427

Abstract

The bacterial microbiota in the skin and intestine of patients with psoriasis were different compared with that of healthy individuals. However, the presence of a distinct blood microbiome in patients with psoriasis is yet to be investigated. In this study, we investigated the [...] Read more.

The bacterial microbiota in the skin and intestine of patients with psoriasis were different compared with that of healthy individuals. However, the presence of a distinct blood microbiome in patients with psoriasis is yet to be investigated. In this study, we investigated the differences in bacterial communities in plasma-derived extracellular vesicles (EVs) between patients with moderate to severe psoriasis (PSOs) and healthy controls (HCs). The plasma EVs from the PSO (PASI > 10) (n = 20) and HC (n = 8) groups were obtained via a series of centrifugations, and patterns were examined and confirmed using transmission electron microscopy (TEM) and EV-specific markers. The taxonomic composition of the microbiota was determined by using full-length 16S ribosomal RNA gene sequencing. The PSO group had lower bacterial diversity and richness compared with HC group. Principal coordinate analysis (PCoA)-based clustering was used to assess diversity and validated dysbiosis for both groups. Differences at the level of amplicon sequence variant (ASV) were observed, suggesting alterations in specific ASVs according to health conditions. The HC group had higher levels of the phylum Firmicutes and Fusobacteria than in the PSO group. The order Lactobacillales, family Brucellaceae, genera Streptococcus, and species Kingella oralis and Aquabacterium parvum were highly abundant in the HC group compared with the PSO group. Conversely, the order Bacillales and the genera Staphylococcus and Sphihgomonas, as well as Ralstonia insidiosa, were more abundant in the PSO group. We further predicted the microbiota functional capacities, which revealed significant differences between the PSO and HC groups. In addition to previous studies on microbiome changes in the skin and gut, we demonstrated compositional differences in the microbe-derived EVs in the plasma of PSO patients. Plasma EVs could be an indicator for assessing the composition of the microbiome of PSO patients. Full article

(This article belongs to the Special Issue Microbiota, Inflammation and Systemic Diseases)

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11 pages, 641 KiB

Open AccessArticle

Gut Leakage Markers in Response to Strenuous Exercise in Patients with Suspected Coronary Artery Disease

by Susanne Kristine Aune, Joanna Cwikiel, Arnljot Flaa, Harald Arnesen, Svein Solheim, Ayodeji Awoyemi, Marius Trøseid, Ingebjørg Seljeflot and Ragnhild Helseth

Cells 2021, 10(9), 2193; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10092193 - 25 Aug 2021

Cited by 6 | Viewed by 1984

Abstract

Elevated levels of gut leakage markers have been shown after strenuous exercise in healthy individuals. Any association between a temporary increase in these markers and the presence of coronary artery disease (CAD) is unknown. We therefore aimed to explore circulating gut leakage markers [...] Read more.

Elevated levels of gut leakage markers have been shown after strenuous exercise in healthy individuals. Any association between a temporary increase in these markers and the presence of coronary artery disease (CAD) is unknown. We therefore aimed to explore circulating gut leakage markers in response to a bout of strenuous exercise in patients with symptoms of CAD. Patients referred to exercise stress testing due to symptoms of CAD were included (n = 287). A maximal exercise ECG stress test was performed and venous blood samples were drawn at rest and within five minutes after, for analysis of soluble cluster of differentiation 14 (sCD14), lipopolysaccharide-binding protein (LBP), intestinal fatty-acid binding protein (I-FABP), lipopolysaccharide (LPS) and gene expression of toll-like receptor 4 (TLR4) in circulating leukocytes. Patients then underwent coronary angiography. LPS, LBP and sCD14 increased significantly after strenuous exercise in patients with symptoms of CAD, suggesting that even short bouts of vigorous exercise are associated with gut leakage. The gene expression of TLR4 decreased significantly after exercise, possibly as a negative feedback to the increase in LPS. There were no differences in exercise-induced changes between the groups of CAD, suggesting gut leakage to be independent of the presence of CAD. Full article

(This article belongs to the Special Issue Microbiota, Inflammation and Systemic Diseases)

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18 pages, 3902 KiB

Open AccessArticle

Identification of Lung and Blood Microbiota Implicated in COVID-19 Prognosis

by Kypros Dereschuk, Lauren Apostol, Ishan Ranjan, Jaideep Chakladar, Wei Tse Li, Mahadevan Rajasekaran, Eric Y. Chang and Weg M. Ongkeko

Cells 2021, 10(6), 1452; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10061452 - 10 Jun 2021

Cited by 10 | Viewed by 3262

Abstract

The implications of the microbiome on Coronavirus disease 2019 (COVID-19) prognosis has not been thoroughly studied. In this study we aimed to characterize the lung and blood microbiome and their implication on COVID-19 prognosis through analysis of peripheral blood mononuclear cell (PBMC) samples, [...] Read more.

The implications of the microbiome on Coronavirus disease 2019 (COVID-19) prognosis has not been thoroughly studied. In this study we aimed to characterize the lung and blood microbiome and their implication on COVID-19 prognosis through analysis of peripheral blood mononuclear cell (PBMC) samples, lung biopsy samples, and bronchoalveolar lavage fluid (BALF) samples. In all three tissue types, we found panels of microbes differentially abundant between COVID-19 and normal samples correlated to immune dysregulation and upregulation of inflammatory pathways, including key cytokine pathways such as interleukin (IL)-2, 3, 5-10 and 23 signaling pathways and downregulation of anti-inflammatory pathways including IL-4 signaling. In the PBMC samples, six microbes were correlated with worse COVID-19 severity, and one microbe was correlated with improved COVID-19 severity. Collectively, our findings contribute to the understanding of the human microbiome and suggest interplay between our identified microbes and key inflammatory pathways which may be leveraged in the development of immune therapies for treating COVID-19 patients. Full article

(This article belongs to the Special Issue Microbiota, Inflammation and Systemic Diseases)

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Review

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18 pages, 1159 KiB

Open AccessReview

The Relevance of the Bacterial Microbiome, Archaeome and Mycobiome in Pediatric Asthma and Respiratory Disorders

by Carolin Baehren, Eleni Buedding, Aliyah Bellm, Frank Schult, Anton Pembaur, Stefan Wirth, Anja Ehrhardt, Friedrich Paulsen, Jan Postberg and Malik Aydin

Cells 2022, 11(8), 1287; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11081287 - 10 Apr 2022

Cited by 5 | Viewed by 2864

Abstract

Bacteria, as well as eukaryotes, principally fungi, of the upper respiratory tract play key roles in the etiopathogenesis of respiratory diseases, whereas the potential role of archaea remains poorly understood. In this review, we discuss the contribution of all three domains of cellular [...] Read more.

Bacteria, as well as eukaryotes, principally fungi, of the upper respiratory tract play key roles in the etiopathogenesis of respiratory diseases, whereas the potential role of archaea remains poorly understood. In this review, we discuss the contribution of all three domains of cellular life to human naso- and oropharyngeal microbiomes, i.e., bacterial microbiota, eukaryotes (mostly fungi), as well as the archaeome and their relation to respiratory and atopic disorders in infancy and adolescence. With this review, we aim to summarize state-of-the-art contributions to the field published in the last decade. In particular, we intend to build bridges between basic and clinical science. Full article

(This article belongs to the Special Issue Microbiota, Inflammation and Systemic Diseases)

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31 pages, 1484 KiB

Open AccessReview

High-Fat, Western-Style Diet, Systemic Inflammation, and Gut Microbiota: A Narrative Review

by Ida Judyta Malesza, Michał Malesza, Jarosław Walkowiak, Nadiar Mussin, Dariusz Walkowiak, Raisa Aringazina, Joanna Bartkowiak-Wieczorek and Edyta Mądry

Cells 2021, 10(11), 3164; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10113164 - 14 Nov 2021

Cited by 202 | Viewed by 17251

Abstract

The gut microbiota is responsible for recovering energy from food, providing hosts with vitamins, and providing a barrier function against exogenous pathogens. In addition, it is involved in maintaining the integrity of the intestinal epithelial barrier, crucial for the functional maturation of the [...] Read more.

The gut microbiota is responsible for recovering energy from food, providing hosts with vitamins, and providing a barrier function against exogenous pathogens. In addition, it is involved in maintaining the integrity of the intestinal epithelial barrier, crucial for the functional maturation of the gut immune system. The Western diet (WD)—an unhealthy diet with high consumption of fats—can be broadly characterized by overeating, frequent snacking, and a prolonged postprandial state. The term WD is commonly known and intuitively understood. However, the strict digital expression of nutrient ratios is not precisely defined. Based on the US data for 1908–1989, the calory intake available from fats increased from 32% to 45%. Besides the metabolic aspects (hyperinsulinemia, insulin resistance, dyslipidemia, sympathetic nervous system and renin-angiotensin system overstimulation, and oxidative stress), the consequences of excessive fat consumption (high-fat diet—HFD) comprise dysbiosis, gut barrier dysfunction, increased intestinal permeability, and leakage of toxic bacterial metabolites into the circulation. These can strongly contribute to the development of low-grade systemic inflammation. This narrative review highlights the most important recent advances linking HFD-driven dysbiosis and HFD-related inflammation, presents the pathomechanisms for these phenomena, and examines the possible causative relationship between pro-inflammatory status and gut microbiota changes. Full article

(This article belongs to the Special Issue Microbiota, Inflammation and Systemic Diseases)

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