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Article ; Online: Respiratory and Gut Microbiome Modification during Respiratory Syncytial Virus Infection: A Systematic Review.

Yagi, Kazuma / Lukacs, Nicholas W / Huffnagle, Gary B / Kato, Hideo / Asai, Nobuhiro

2024 Volume 16, Issue 2

Abstract: Background: Respiratory syncytial virus (RSV) infection is a major cause of lower respiratory tract infection, especially in infants, and increases the risk of recurrent wheezing and asthma. Recently, researchers have proposed a possible association ... ...

Abstract	Background: Respiratory syncytial virus (RSV) infection is a major cause of lower respiratory tract infection, especially in infants, and increases the risk of recurrent wheezing and asthma. Recently, researchers have proposed a possible association between respiratory diseases and microbiome alterations. However, this connection has not been fully established. Herein, we conducted a systematic literature review to evaluate the reported evidence of microbiome alterations in patients with RSV infection. Methods: The systematic literature review on the association between RSV and microbiome in humans was conducted by searching PubMed, EMBASE, Scopus, and CINAHL from 2012 until February 2022. The results were analyzed qualitatively, focusing on the relationship between microbiome and RSV infection with available key microbiome-related parameters. Results: In the 405 articles identified by searching databases, 12 (Respiratory tract: 9, Gut: 2, Both: 1) articles in line with the research aims were eligible for this qualitative review. The types of samples for the respiratory tract microbiome and the sequencing methods utilized varied from study to study. This review revealed that the overall microbial composition in both the respiratory tract and gut in RSV-infected patients was different from that in healthy controls. Our generated results demonstrated an increase in the abundance of Conclusions: The respiratory tract and gut microbiome changed in patients with RSV infection. Further research with a well-organized longitudinal design is warranted to clarify the impact of microbiome alterations on disease pathogenesis.
MeSH term(s)	Infant ; Humans ; Respiratory Syncytial Virus Infections ; Gastrointestinal Microbiome ; Respiratory Tract Infections ; Microbiota ; Asthma/complications
Language	English
Publishing date	2024-01-31
Publishing country	Switzerland
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16020220
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Article ; Online: The Lung Microbiome during Health and Disease.

Yagi, Kazuma / Huffnagle, Gary B / Lukacs, Nicholas W / Asai, Nobuhiro

International journal of molecular sciences

2021 Volume 22, Issue 19

Abstract: Healthy human lungs have traditionally been considered to be a sterile organ. However, culture-independent molecular techniques have reported that large numbers of microbes coexist in the lung and airways. The lungs harbor diverse microbial composition ... ...

Abstract	Healthy human lungs have traditionally been considered to be a sterile organ. However, culture-independent molecular techniques have reported that large numbers of microbes coexist in the lung and airways. The lungs harbor diverse microbial composition that are undetected by previous approaches. Many studies have found significant differences in microbial composition between during health and respiratory disease. The lung microbiome is likely to not only influence susceptibility or causes of diseases but be affected by disease activities or responses to treatment. Although lung microbiome research has some limitations from study design to reporting, it can add further dimensionality to host-microbe interactions. Moreover, there is a possibility that extending understanding to the lung microbiome with new multiple omics approaches would be useful for developing both diagnostic and prognostic biomarkers for respiratory diseases in clinical settings.
MeSH term(s)	Animals ; Host-Pathogen Interactions ; Humans ; Lung/microbiology ; Lung Diseases/microbiology ; Microbiota
Language	English
Publishing date	2021-10-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms221910872
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Article ; Online: Early-Life Lung and Gut Microbiota Development and Respiratory Syncytial Virus Infection.

Yagi, Kazuma / Asai, Nobuhiro / Huffnagle, Gary B / Lukacs, Nicholas W / Fonseca, Wendy

Frontiers in immunology

2022 Volume 13, Page(s) 877771

Abstract: Several environmental factors can influence the development and establishment of the early-life microbiota. For example, exposure to different environmental factors from birth to childhood will shape the lung and gut microbiota and the development of the ...

Abstract	Several environmental factors can influence the development and establishment of the early-life microbiota. For example, exposure to different environmental factors from birth to childhood will shape the lung and gut microbiota and the development of the immune system, which will impact respiratory tract infection and widespread disease occurrence during infancy and later in life. Respiratory syncytial virus (RSV) infects most infants by the age of two and is the primary cause of bronchiolitis in children worldwide. Approximately a third of infants hospitalized with bronchiolitis develop asthma later in life. However, it is unclear what factors increase susceptibility to severe RSV-bronchiolitis and the subsequent asthma development. In recent years, the role of the gut and lung microbiota in airway diseases has received increased interest, and more studies have focused on this field. Different epidemiological studies and experimental animal models have associated early-life gut microbiota dysbiosis with an increased risk of lung disease later in life. This work will review published evidence that correlated environmental factors that affect the early-life microbiota composition and their role in developing severe RSV infection.
MeSH term(s)	Animals ; Asthma/etiology ; Bronchiolitis/complications ; Child ; Gastrointestinal Microbiome ; Humans ; Lung ; Microbiota ; Respiratory Syncytial Virus Infections ; Respiratory Syncytial Virus, Human
Language	English
Publishing date	2022-04-04
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.877771
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Article ; Online: Early-life pulmonary viral infection leads to long-term functional and lower airway structural changes in the lungs.

Malinczak, Carrie-Anne / Fonseca, Wendy / Hrycaj, Steven M / Morris, Susan B / Rasky, Andrew J / Yagi, Kazuma / Wellik, Deneen M / Ziegler, Steven F / Zemans, Rachel L / Lukacs, Nicholas W

American journal of physiology. Lung cellular and molecular physiology

2024 Volume 326, Issue 3, Page(s) L280–L291

Abstract: Early-life respiratory virus infections have been correlated with enhanced development of childhood asthma. In particular, significant numbers of respiratory syncytial virus (RSV)-hospitalized infants go on to develop lung disease. It has been suggested ... ...

Abstract	Early-life respiratory virus infections have been correlated with enhanced development of childhood asthma. In particular, significant numbers of respiratory syncytial virus (RSV)-hospitalized infants go on to develop lung disease. It has been suggested that early-life viral infections may lead to altered lung development or repair that negatively impacts lung function later in life. Our data demonstrate that early-life RSV infection modifies lung structure, leading to decreased lung function. At 5 wk postneonatal RSV infection, significant defects are observed in baseline pulmonary function test (PFT) parameters consistent with decreased lung function as well as enlarged alveolar spaces. Lung function changes in the early-life RSV-infected group continue at 3 mo of age. The altered PFT and structural changes induced by early-life RSV were mitigated in
MeSH term(s)	Humans ; Infant ; Animals ; Mice ; Respiratory Syncytial Virus Infections ; Lung/pathology ; Pneumonia/complications ; Lung Diseases/complications ; Respiratory Syncytial Virus, Human ; Mice, Inbred BALB C
Language	English
Publishing date	2024-01-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	1013184-x
ISSN	1522-1504 ; 1040-0605
ISSN (online)	1522-1504
ISSN	1040-0605
DOI	10.1152/ajplung.00300.2023
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Article ; Online: A solitary pulmonary nodule caused by Mycobacterium avium with pleural effusion and pleuritis after transbronchial biopsy: a case report.

Nukaga, Shigenari / Murakami, Hiroaki / Yagi, Kazuma / Satomi, Ryosuke / Oyama, Takahiko / Maeshima, Arafumi / Oyamada, Yoshitaka

Journal of medical case reports

2021 Volume 15, Issue 1, Page(s) 342

Abstract: Background: Pleural effusion and pleuritis are uncommon manifestations of Mycobacterium avium complex pulmonary disease. Pleuritis caused by Mycobacterium avium complex pulmonary disease presenting as a solitary pulmonary nodule is extremely rare. The ... ...

Abstract	Background: Pleural effusion and pleuritis are uncommon manifestations of Mycobacterium avium complex pulmonary disease. Pleuritis caused by Mycobacterium avium complex pulmonary disease presenting as a solitary pulmonary nodule is extremely rare. The pathogenesis of Mycobacterium avium complex pleuritis has not been elucidated. However, it has been suggested that secondary spontaneous pneumothorax from Mycobacterium avium complex pulmonary disease is one of the causes of Mycobacterium avium complex pleuritis. Case presentation: A 67-year-old Japanese woman who presented with a solitary pulmonary nodule developed a transient pneumothorax after transbronchial biopsy. A definitive diagnosis of solitary pulmonary nodule could not be made on bronchoscopy, so video-assisted thoracoscopic surgery was performed 1 month after bronchoscopy. On the day of hospitalization for the procedure, a left-sided pleural effusion appeared on a chest radiograph. Thickening of the parietal and visceral pleura and numerous scattered white small granules were seen on thoracoscopy. Histologic examination of the resected left lower lobe and a biopsy of the parietal pleura showed Mycobacterium avium complex solitary pulmonary nodule and Mycobacterium avium complex pleuritis. Conclusion: Iatrogenic pneumothorax can be a cause of pleuritis in a patient with Mycobacterium avium complex pulmonary disease. Clinicians should watch for the appearance of secondary pleuritis after transbronchial biopsy even in a patient with localized disease such as Mycobacterium avium complex solitary pulmonary nodule.
MeSH term(s)	Aged ; Biopsy ; Female ; Humans ; Mycobacterium avium ; Pleural Effusion/etiology ; Pleurisy/etiology ; Solitary Pulmonary Nodule/diagnostic imaging
Language	English
Publishing date	2021-07-11
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	2269805-X
ISSN	1752-1947 ; 1752-1947
ISSN (online)	1752-1947
ISSN	1752-1947
DOI	10.1186/s13256-021-02929-9
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Article ; Online: Fatal Disseminated Tuberculosis and Concurrent Disseminated Cryptococcosis in a Ruxolitinib-treated Patient with Primary Myelofibrosis: A Case Report and Literature Review.

Ogai, Asuka / Yagi, Kazuma / Ito, Fumimaro / Domoto, Hideharu / Shiomi, Tetsuya / Chin, Kenko

Internal medicine (Tokyo, Japan)

2021 Volume 61, Issue 8, Page(s) 1271–1278

Abstract: Ruxolitinib, a Janus kinase inhibitor, improves symptoms in patients with myelofibrosis. However, its association with the development of opportunistic infections has been a concern. We herein report a 71-year-old man with primary myelofibrosis who ... ...

Abstract	Ruxolitinib, a Janus kinase inhibitor, improves symptoms in patients with myelofibrosis. However, its association with the development of opportunistic infections has been a concern. We herein report a 71-year-old man with primary myelofibrosis who developed disseminated tuberculosis and concurrent disseminated cryptococcosis during ruxolitinib treatment. We also reviewed the literature on disseminated tuberculosis and/or cryptococcosis associated with ruxolitinib treatment. This is the first case of disseminated tuberculosis and concurrent disseminated cryptococcosis during treatment with ruxolitinib. We therefore suggest considering not only disseminated tuberculosis but also cryptococcosis in the differential diagnosis of patients with abnormal pulmonary shadows during ruxolitinib treatment.
MeSH term(s)	Aged ; Cryptococcosis/complications ; Cryptococcosis/diagnosis ; Cryptococcosis/drug therapy ; Granuloma ; Humans ; Male ; Nitriles ; Primary Myelofibrosis/complications ; Primary Myelofibrosis/drug therapy ; Pyrazoles ; Pyrimidines ; Tuberculosis, Miliary
Chemical Substances	Nitriles ; Pyrazoles ; Pyrimidines ; ruxolitinib (82S8X8XX8H)
Language	English
Publishing date	2021-09-25
Publishing country	Japan
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	32371-8
ISSN	1349-7235 ; 0021-5120 ; 0918-2918
ISSN (online)	1349-7235
ISSN	0021-5120 ; 0918-2918
DOI	10.2169/internalmedicine.6436-20
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Article ; Online: Clinical features of Japanese patients with gastrointestinal long-COVID symptoms.

Yagi, Kazuma / Asakura, Takanori / Terai, Hideki / Ohgino, Keiko / Masaki, Katsunori / Namkoong, Ho / Chubachi, Shotaro / Miyata, Jun / Kawada, Ichiro / Kodama, Nobuhiro / Sakamoto, Satoshi / Umeda, Akira / Ishiguro, Takashi / Ishii, Makoto / Fukunaga, Koichi

JGH open : an open access journal of gastroenterology and hepatology

2023 Volume 7, Issue 12, Page(s) 998–1002

Abstract: Gastrointestinal (GI) long-COVID symptoms, including diarrhea and abdominal pain, have been reported in patients with long-COVID. However, the clinical features of patients with GI long-COVID symptoms remain unclear. We conducted a large-scale ... ...

Abstract	Gastrointestinal (GI) long-COVID symptoms, including diarrhea and abdominal pain, have been reported in patients with long-COVID. However, the clinical features of patients with GI long-COVID symptoms remain unclear. We conducted a large-scale prospective cohort study focusing on the clinical characteristics of patients with GI long-COVID symptoms in Japan. Among 943 COVID-19 patients, 58 patients (6.2%) had GI long-COVID symptoms. The health-related quality of life (QOL) parameters (the Short Form-8 [SF-8] and Euro Quality of Life 5 Dimensions 5 level [EQ-5D-5L]) at 12 months after diagnosis in patients with GI long-COVID symptoms were significantly lower than in those without GI long-COVID symptoms (
Language	English
Publishing date	2023-12-06
Publishing country	Australia
Document type	Journal Article
ISSN	2397-9070
ISSN (online)	2397-9070
DOI	10.1002/jgh3.13006
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Article ; Online: A steroid-resistant cockroach allergen model is associated with lung and cecal microbiome changes.

Asai, Nobuhiro / Ethridge, Alexander D / Fonseca, Wendy / Yagi, Kazuma / Rasky, Andrew J / Morris, Susan B / Falkowski, Nicole R / Huang, Yvonne J / Huffnagle, Gary B / Lukacs, Nicholas W

Physiological reports

2023 Volume 11, Issue 13, Page(s) e15761

Abstract: The pathogenesis of asthma has been partially linked to lung and gut microbiome. We utilized a steroid-resistant chronic model of cockroach antigen-induced (CRA) asthma with corticosteroid (fluticasone) treatment to examine lung and gut microbiome during ...

Abstract	The pathogenesis of asthma has been partially linked to lung and gut microbiome. We utilized a steroid-resistant chronic model of cockroach antigen-induced (CRA) asthma with corticosteroid (fluticasone) treatment to examine lung and gut microbiome during disease. The pathophysiology assessment demonstrated that mucus and airway hyperresponsiveness were increased in the chronic CRA with no alteration in the fluticasone (Flut)-treated group, demonstrating steroid resistance. Analysis of mRNA from lungs showed no decrease of MUC5AC or Gob5 in the Flut-treated group. Furthermore, flow-cytometry in lung tissue showed eosinophils and neutrophils were not significantly reduced in the Flut-treated group compared to the chronic CRA group. When the microbiome profiles were assessed, data showed that only the Flut-treated animals were significantly different in the gut microbiome. Finally, a functional analysis of cecal microbiome metabolites using PiCRUSt showed several biosynthetic pathways were significantly enriched in the Flut-treated group, with tryptophan pathway verified by ELISA with increased kynurenine in homogenized cecum samples. While the implications of these data are unclear, they may suggest a significant impact of steroid treatment on future disease pathogenesis through microbiome and associated metabolite pathway changes.
MeSH term(s)	Animals ; Lung/pathology ; Asthma/etiology ; Allergens ; Fluticasone ; Microbiota ; Cockroaches
Chemical Substances	Allergens ; Fluticasone (CUT2W21N7U)
Language	English
Publishing date	2023-07-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2724325-4
ISSN	2051-817X ; 2051-817X
ISSN (online)	2051-817X
ISSN	2051-817X
DOI	10.14814/phy2.15761
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Article ; Online: Comparing minimum inhibitory concentrations of amikacin for pulmonary Mycobacterium avium complex disease: An analysis of culture media differences.

Morita, Atsuho / Namkoong, Ho / Uwamino, Yoshifumi / Mitarai, Satoshi / Aono, Akio / Asakura, Takanori / Yagi, Kazuma / Tanaka, Hiromu / Azekawa, Shuhei / Nakagawara, Kensuke / Kaji, Masanori / Nagao, Genta / Kamata, Hirofumi / Matsushita, Hiromichi / Fukunaga, Koichi / Hasegawa, Naoki

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy

2023 Volume 30, Issue 2, Page(s) 159–163

Abstract: Mycobacterium avium complex (MAC) is considered a paramount microbe, especially in East Asia, including Japan. The commonly used commercial Minimum Inhibitory Concentrations (MIC) assay using Middlebrook 7H9 (7H9) medium deviates from the latest Clinical ...

Abstract	Mycobacterium avium complex (MAC) is considered a paramount microbe, especially in East Asia, including Japan. The commonly used commercial Minimum Inhibitory Concentrations (MIC) assay using Middlebrook 7H9 (7H9) medium deviates from the latest Clinical and Laboratory Standards Institute (CLSI) guidelines. Alternatively, measurement with cation-adjusted Mueller-Hinton broth (CAMHB) that conforms to CLSI standards is not yet widely available. Following the approval and commercialization of amikacin liposome inhalation suspension (ALIS) in 2021, a more precise evaluation of amikacin (AMK) susceptibility in MAC is necessary for treatment decisions. In the present study, 33 sputum samples were extracted from 27 patients, and MICs of AMK were compared between the frequently used 7H9 and the recommended CAMHB of the isolated MAC strains. The history of exposure to aminoglycosides for each sample was also added as clinical information. The findings indicated that there was only an 18% concordance rate in MIC between the two media, with 19 samples (58%) indicating lower MICs in 7H9 relative to CAMHB. The 17 samples had a history of exposure to aminoglycosides for periods ranging from 1.5 to 28 months. Specifically, 10 samples were exposed to amikacin by inhalation and intravenous injection, and the remaining seven samples had a history of ALIS inhalation. Samples with a prior utilization of aminoglycosides were significantly predisposed to developing resistance to ALIS compared to those without such a history (P = 0.046). Physicians are encouraged to scrutinize the findings of susceptibility testing utilizing CLSI-endorsed MIC assay using CAMHB medium to ascertain the optimal therapeutic approach.
MeSH term(s)	Humans ; Amikacin/pharmacology ; Amikacin/therapeutic use ; Mycobacterium avium Complex ; Mycobacterium avium-intracellulare Infection/drug therapy ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Lung Diseases/microbiology ; Culture Media ; Microbial Sensitivity Tests
Chemical Substances	Amikacin (84319SGC3C) ; Anti-Bacterial Agents ; Culture Media
Language	English
Publishing date	2023-09-16
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1355399-9
ISSN	1437-7780 ; 1341-321X
ISSN (online)	1437-7780
ISSN	1341-321X
DOI	10.1016/j.jiac.2023.09.016
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Zs.A 5236: Show issues

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Article ; Online: Sex-associated early-life viral innate immune response is transcriptionally associated with chromatin remodeling of type-I IFN-inducible genes.

Malinczak, Carrie-Anne / Fonseca, Wendy / Mire, Mohamed M / Parolia, Abhijit / Chinnaiyan, Arul / Rasky, Andrew J / Morris, Susan / Yagi, Kazuma / Bermick, Jennifer R / Lukacs, Nicholas W

Mucosal immunology

2023 Volume 16, Issue 5, Page(s) 578–592

Abstract: This study investigates sex-associated systemic innate immune differences by examining bone marrow-derived dendritic cells (BMDCs). BMDC grown from 7-day-old mice show enhanced type-I interferon (IFN) signaling in female compared to male BMDC. Upon ... ...

Abstract	This study investigates sex-associated systemic innate immune differences by examining bone marrow-derived dendritic cells (BMDCs). BMDC grown from 7-day-old mice show enhanced type-I interferon (IFN) signaling in female compared to male BMDC. Upon respiratory syncytial virus (RSV) infection of 7-day-old mice, a significantly altered phenotype of BMDC at 4 weeks post-infection is observed in a sex-dependent manner. The alterations include heightened Ifnb/ interleukin (Il12a) and enhanced IFNAR1+ expression in BMDC from early-life RSV-infected female mice that leads to increased IFN-γ production by T cells. Phenotypic differences were verified upon pulmonary sensitization whereby EL-RSV male-derived BMDC promoted enhanced T helper 2/17 responses and exacerbated disease upon RSV infection while EL-RSV/F BMDC sensitization was relatively protective. Assay for transposase-accessible chromatin using sequencing analysis (ATAC-seq) demonstrated that EL-RSV/F BMDC had enhanced chromatin accessibility near type-I immune genes with JUN, STAT1/2, and IRF1/8 transcription factors predicted to have binding sites in accessible regions. Importantly, ATAC-seq of human cord blood-derived monocytes displayed a similar sex-associated chromatin landscape with female-derived monocytes having more accessibility in type-I immune genes. These studies enhance our understanding of sex-associated differences in innate immunity by epigenetically controlled transcriptional programs amplified by early-life infection in females via type-I immunity.
MeSH term(s)	Male ; Mice ; Female ; Humans ; Animals ; Chromatin Assembly and Disassembly ; Respiratory Syncytial Virus Infections ; Immunity, Innate ; Lung ; Interferon Type I/metabolism ; Chromatin/genetics ; Chromatin/metabolism
Chemical Substances	Interferon Type I ; Chromatin
Language	English
Publishing date	2023-06-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2411370-0
ISSN	1935-3456 ; 1933-0219
ISSN (online)	1935-3456
ISSN	1933-0219
DOI	10.1016/j.mucimm.2023.06.002
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