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Article: Analysis of the gut microbiome to validate a mouse model of pellagra.

Susai, Natsumi / Kuroita, Tomohiro / Kuronuma, Koji / Yoshioka, Takeshi

Bioscience of microbiota, food and health

2022 Volume 41, Issue 2, Page(s) 73–82

Abstract: Pellagra is caused by an abnormal intake and/or use of niacin, but its phenotypes are diverse. The phenotypes of pellagra can also be atypical, such as nausea. We previously reported a mouse model of pellagra-related nausea. However, the mechanism of ... ...

Abstract	Pellagra is caused by an abnormal intake and/or use of niacin, but its phenotypes are diverse. The phenotypes of pellagra can also be atypical, such as nausea. We previously reported a mouse model of pellagra-related nausea. However, the mechanism of this model is unclear. In this study, we found that the gut microbiota, which is thought to be a source of niacin, played an important role in the development of pellagra-related nausea in germ-free mice. We also investigated the gut microbiome. We compared urinary niacin metabolite levels and the dermal response between mice fed a normal diet and those fed a low-niacin diet to investigate the putative trigger of pellagra. Epoxyeicosatrienoic and hydroxyeicosatetraenoic acid levels were higher in mice fed a low-niacin diet compared with those fed a normal diet. Furthermore, histological studies indicated a dermatological response to the low-niacin diet. Interestingly, higher levels of oxidised fatty acids in response to the germ-free state were also observed. These findings indicate successful establishment of our newly established mouse model of pellagra via the gut microbiota. We believe that this model could enable the discovery of the putative cause of pellagra and phenotypes of pellagra that have not been recognised yet.
Language	English
Publishing date	2022-01-24
Publishing country	Japan
Document type	Journal Article
ISSN	2186-6953
ISSN	2186-6953
DOI	10.12938/bmfh.2021-059
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Article: Protective effect of

Kuronuma, Koji / Susai, Natsumi / Kuroita, Tomohiro / Yoshioka, Takeshi / Saito, Atsushi / Chiba, Hirofumi

Bioscience of microbiota, food and health

2023 Volume 42, Issue 3, Page(s) 195–202

Abstract: Pellagra is caused by abnormal intake and/or use of nicotinic acid and is known in part to be induced by the use of medications such as isoniazid or pirfenidone. We previously investigated atypical phenotypes of pellagra, such as nausea, using a mouse ... ...

Abstract	Pellagra is caused by abnormal intake and/or use of nicotinic acid and is known in part to be induced by the use of medications such as isoniazid or pirfenidone. We previously investigated atypical phenotypes of pellagra, such as nausea, using a mouse model of pellagra and found that gut microbiota play an important role in the development of these phenotypes. Here, we investigated the effect of
Language	English
Publishing date	2023-03-09
Publishing country	Japan
Document type	Journal Article
ISSN	2186-6953
ISSN	2186-6953
DOI	10.12938/bmfh.2022-042
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Article ; Online: Pneumocystis jirovecii

Takahashi, Tomoyuki / Saito, Atsushi / Kuronuma, Koji / Nishikiori, Hirotaka / Chiba, Hirofumi

Medicina (Kaunas, Lithuania)

2022 Volume 58, Issue 9

Abstract: Here, we report two cases of patients with interstitial pneumonia (IP) on steroids who ... ...

Abstract	Here, we report two cases of patients with interstitial pneumonia (IP) on steroids who developed
MeSH term(s)	Aged ; COVID-19/complications ; Female ; Glucans/therapeutic use ; Humans ; Lung Diseases, Interstitial/complications ; Lung Diseases, Interstitial/drug therapy ; Male ; Pneumocystis carinii/genetics ; Pneumonia, Pneumocystis/complications ; Pneumonia, Pneumocystis/drug therapy ; Prednisolone/therapeutic use ; Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use
Chemical Substances	Glucans ; Trimethoprim, Sulfamethoxazole Drug Combination (8064-90-2) ; Prednisolone (9PHQ9Y1OLM)
Language	English
Publishing date	2022-08-24
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2188113-3
ISSN	1648-9144 ; 1010-660X
ISSN (online)	1648-9144
ISSN	1010-660X
DOI	10.3390/medicina58091151
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Article: Gut microbiota and metabolites in patients with COVID-19 are altered by the type of SARS-CoV-2 variant.

Yokoyama, Yoshihiro / Ichiki, Tomoko / Yamakawa, Tsukasa / Tsuji, Yoshihisa / Kuronuma, Koji / Takahashi, Satoshi / Narimatsu, Eichi / Katanuma, Akio / Nakase, Hiroshi

Frontiers in microbiology

2024 Volume 15, Page(s) 1358530

Abstract: Introduction: Patients with COVID-19 have dysbiosis of the intestinal microbiota with altered metabolites in the stool. However, it remains unclear whether the differences among SARS-CoV-2 variants lead to differences in intestinal microbiota and ... ...

Abstract	Introduction: Patients with COVID-19 have dysbiosis of the intestinal microbiota with altered metabolites in the stool. However, it remains unclear whether the differences among SARS-CoV-2 variants lead to differences in intestinal microbiota and metabolites. Thus, we compared the microbiome and metabolome changes for each SARS-CoV-2 variant in patients with COVID-19. Materials and methods: We conducted a multicenter observational study of patients with COVID-19 and performed fecal microbiome, metabolome, and calprotectin analyses and compared the results among the different SARS-CoV-2 variants. Results: Twenty-one patients with COVID-19 were enrolled and stratified according to the SARS-CoV-2 strain: six with the Alpha, 10 with the Delta, and five with the Omicron variant. Fecal microbiome analysis showed that α-diversity was reduced in the order of the Omicron, Delta, and Alpha variants ( Conclusion: The intestinal microbiota of patients with COVID-19 varies depending on the SARS-CoV-2 variant. Dysbiosis of the intestinal microbiota due to differences in SARS-CoV-2 variants causes a decrease in intestinal short-chain fatty acids.
Language	English
Publishing date	2024-03-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2024.1358530
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Article ; Online: The impact of respiratory reactance in oscillometry on survival in patients with idiopathic pulmonary fibrosis.

Ishikawa, Tatsuru / Nishikiori, Hirotaka / Mori, Yuki / Fujino, Keiko / Saito, Atsushi / Takahashi, Mamoru / Kuronuma, Koji / Hinotsu, Shiro / Chiba, Hirofumi

BMC pulmonary medicine

2024 Volume 24, Issue 1, Page(s) 10

Abstract: Background: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. Pulmonary function tests (PFTs) aid in evaluating the disease status of IPF. The clinical significance of oscillometry measurements in interstitial lung ... ...

Abstract	Background: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. Pulmonary function tests (PFTs) aid in evaluating the disease status of IPF. The clinical significance of oscillometry measurements in interstitial lung diseases has recently been reported. Our previous study showed that respiratory reactance (Xrs) measured by oscillometry reflected disease severity and predicted subsequent lung capacity decline in patients with IPF. However, the direct impact of Xrs on survival needs to be determined, and there are currently no reference values in oscillometry to predict prognosis. Therefore, this study aimed to investigate the association between oscillometry measurements, particularly Xrs, and survival in patients with IPF and to determine the cutoff values of Xrs that predict 3-year survival. Methods: We analyzed the relationship between the measured values of PFT and oscillometry derived from 178 patients with IPF. Univariate and multivariate Cox proportional hazards analyses were performed to investigate the relationships between clinical indices at the time of the first oscillometry and survival. We performed the time-dependent receiver operating characteristic (ROC) curve analysis to set the optimized cutoff values of Xrs for 3-year survival prediction. We examined the discriminating power of cutoff values of Xrs on survival using the Kaplan-Meier method and the log-rank test. Results: Xrs components, especially in the inspiratory phase (In), significantly correlated with the PFT values. In the multivariate analyses, Xrs (all of reactance at 5 Hz [X5], resonant frequency [Fres], and low-frequency reactance area [ALX] in the inspiratory phase) had a significant impact on survival (X5, p = 0.003; Fres, p = 0.016; ALX, p = 0.003) independent of age, sex, and other prognostic factors derived from the univariate analysis. The area under the ROC curve was 0.765, 0.759, and 0.766 for X5 In, Fres In, and ALX In, with cutoff values determined at - 0.98, 10.67, and 5.32, respectively. We found significant differences in survival after dividing patients using each of the cutoff values of Xrs. Conclusions: In patients with IPF, Xrs measured by oscillometry significantly impacted survival. We also determined the cutoff values of Xrs to discriminate patients with poor prognoses.
MeSH term(s)	Humans ; Airway Resistance ; Oscillometry/methods ; Lung ; Respiratory Function Tests/methods ; Idiopathic Pulmonary Fibrosis/diagnosis
Language	English
Publishing date	2024-01-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2059871-3
ISSN	1471-2466 ; 1471-2466
ISSN (online)	1471-2466
ISSN	1471-2466
DOI	10.1186/s12890-023-02776-y
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Article ; Online: Serum Testosterone Is Associated With the Severity of COVID-19.

Suzuki, Ema / Kuronuma, Koji / Murai, Ryosei / Fujiya, Yoshihiro / Saito, Atsushi / Chiba, Hirofumi / Takahashi, Satoshi

In vivo (Athens, Greece)

2023 Volume 37, Issue 5, Page(s) 2314–2319

Abstract: Background/aim: Coronavirus disease 2019 (COVID-19) is more likely to be severe in men than in women. Its association with sex hormones as an aggravating factor for male patients has been attracting attention. This study aimed to investigate whether ... ...

Abstract	Background/aim: Coronavirus disease 2019 (COVID-19) is more likely to be severe in men than in women. Its association with sex hormones as an aggravating factor for male patients has been attracting attention. This study aimed to investigate whether serum testosterone is associated with the aggravation of COVID-19. Patients and methods: Serum testosterone concentrations in 116 male patients with COVID-19 and residual serum were measured and examined upon their admission to Sapporo Medical University Hospital between February 1, 2020 and March 31, 2021. Results: Blood samples collected from these patients with COVID-19 were analyzed. The serum testosterone levels were 2.19±1.35, 1.29±0.88, and 0.75±0.58 ng/ml in mild, moderate, and severe groups, respectively. Patients with severe COVID-19 on admission had lower testosterone levels (p<0.001). At a cutoff level of 1.31 ng/ml, the area under the curve for the comparison of severe with non-severe cases was 0.825. Furthermore, serum testosterone levels negatively correlated with C-reactive protein and serum amyloid A levels but positively correlated with calcium, zinc, C3, and C4. Conclusion: In male patients with COVID-19, low serum testosterone levels correlated with disease severity, accompanied by a strong inflammatory reaction and proportion of complement consumption.
MeSH term(s)	Humans ; Male ; Female ; COVID-19 ; C-Reactive Protein ; Gonadal Steroid Hormones ; Testosterone
Chemical Substances	C-Reactive Protein (9007-41-4) ; Gonadal Steroid Hormones ; Testosterone (3XMK78S47O)
Language	English
Publishing date	2023-08-29
Publishing country	Greece
Document type	Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
DOI	10.21873/invivo.13334
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Zs.A 2288: Show issues

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Article ; Online: The Soluble Lectin Families as Novel Biomarkers for COVID-19 Pneumonia.

Takenaka, Haruka / Saito, Atsushi / Kuronuma, Koji / Moniwa, Keigo / Nishikiori, Hirotaka / Takahashi, Satoshi / Chiba, Hirofumi

In vivo (Athens, Greece)

2023 Volume 37, Issue 4, Page(s) 1721–1728

Abstract: Background/aim: The lung-specific soluble lectins, SP-A and SP-D have been clinically used to diagnose interstitial lung disease, but their clinical significance in COVID-19 remains controversial. This study was undertaken to determine their association ...

Abstract	Background/aim: The lung-specific soluble lectins, SP-A and SP-D have been clinically used to diagnose interstitial lung disease, but their clinical significance in COVID-19 remains controversial. This study was undertaken to determine their association with other lectins (MBL and FCN1), disease severity, and radiographs in COVID-19 patients. Patients and methods: A total of 131 patients with COVID-19 admitted in the Sapporo Medical University Hospital between May 22 and September 19, 2021, were enrolled in the study. Data including demographics, medical history, symptoms, signs, laboratory findings, and radiological images were collected from the patients' medical records. Chest computed tomography (CT) scanning was performed at admission. Serum levels of surfactant protein A and D (SP-A and SP-D), mannose-binding lectin (MBL) and ficolin1 (FCN1) were measured using enzyme-linked immunosorbent assay (ELISA) kits. Results: Compared to the control group, the COVID-19 group had significantly higher serum SP-A and FCN1 levels on admission (SP-A: 59.60±38.89 vs. 35.61±11.22 ng/ml; p<0.01, FCN1: 542.45±506.04 vs. 250.6±161.1 ng/ml; p<0.01). The severe group in COVID-19 had significantly higher serum SP-D and lower MBL levels than the non-severe group (SP-D: 141.7±155.7 vs. 61.41±54.54 ng/ml; p<0.01, MBL: 1,670±1,240 vs. 2,170±1,140 ng/ml; p<0.05). SP-D strongly reflected the degree of imaging findings, whereas SP-A showed a significant correlation, albeit slightly weaker than SP-D. Conversely, MBL and FNC1 were not significantly correlated with imaging findings. Conclusion: Among soluble serum lectins, SP-A and SP-D may be more sensitive to CT findings than reported disease biomarkers such as IL-6, LDH, and CRP due to their lung-specific characteristics.
MeSH term(s)	Humans ; Lectins ; Pulmonary Surfactant-Associated Protein D/metabolism ; COVID-19/diagnosis ; Biomarkers ; Lung/diagnostic imaging ; Lung/metabolism
Chemical Substances	Lectins ; Pulmonary Surfactant-Associated Protein D ; Biomarkers
Language	English
Publishing date	2023-06-25
Publishing country	Greece
Document type	Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
DOI	10.21873/invivo.13259
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Zs.A 2288: Show issues

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Article ; Online: Factors affecting the sensitivity of quantitative severe acute respiratory syndrome coronavirus 2 antigen test.

Sato, Yuki / Murai, Ryosei / Kobayashi, Ryo / Togashi, Atsuo / Fujiya, Yoshihiro / Kuronuma, Koji / Takahashi, Satoshi

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

2023 Volume 29, Issue 8, Page(s) 754–758

Abstract: Introduction: The accuracy of nucleic acid amplification tests (NAATs) is affected by various factors; however, studies examining the factors affecting the accuracy of quantitative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen ... ...

Abstract	Introduction: The accuracy of nucleic acid amplification tests (NAATs) is affected by various factors; however, studies examining the factors affecting the accuracy of quantitative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen test (QAT) are limited. Methods: A total of 347 nasopharyngeal samples were collected from patients with coronavirus disease 2019 (COVID-19), and the date of onset was obtained from the electronic medical records. The SARS-CoV-2 antigen level was measured using Lumipulse Presto SARS-CoV-2 Ag (Presto), while NAAT was performed using the Ampdirect 2019-nCoV Detection Kit. Results: Presto had a sensitivity rate of 95.1% (95% confidence interval: 92.8-97.4) in detecting the SARS-CoV-2 antigen in 347 samples. The number of days from symptom onset to sample collection was negatively correlated with the amount of antigen (r = -0.515) and sensitivity of Presto (r = -0.711). The patients' age was lower in the Presto-negative samples (median age, 39 years) compared with that in the Presto-positive samples (median age, 53 years; p < 0.01). A significant positive correlation was observed between age (excluding teenagers) and Presto sensitivity (r = 0.764). Meanwhile, no association was found between the mutant strain, sex, and Presto results. Conclusion: Presto is useful for the accurate diagnosis of COVID-19 owing to its high sensitivity when the number of days from symptom onset to sample collection is within 12 days. Furthermore, age may affect the results of Presto, and this tool has a relatively low sensitivity in younger patients.
MeSH term(s)	Adolescent ; Humans ; Adult ; Middle Aged ; COVID-19/diagnosis ; SARS-CoV-2/genetics ; Sensitivity and Specificity ; COVID-19 Testing ; Antigens, Viral
Chemical Substances	Antigens, Viral
Language	English
Publishing date	2023-04-13
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.2023.04.005
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Zs.A 5236: Show issues

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Article ; Online: Immunogenicity of pneumococcal vaccines in comorbid autoimmune and chronic respiratory diseases.

Kuronuma, Koji / Takahashi, Hiroki

Human vaccines & immunotherapeutics

2019 Volume 15, Issue 4, Page(s) 859–862

Abstract: Streptococcus pneumoniae causes pneumonia, meningitis, otitis media, and bacteremia. The mortality and morbidity of invasive pneumococcal disease are high among adults aged >65 years or those with underlying chronic or immunosuppressive conditions. A ... ...

Abstract	Streptococcus pneumoniae causes pneumonia, meningitis, otitis media, and bacteremia. The mortality and morbidity of invasive pneumococcal disease are high among adults aged >65 years or those with underlying chronic or immunosuppressive conditions. A recent systematic review showed that patients treated with immunosuppressive agents have impaired immune responses to pneumococcal conjugate vaccine (PCV) and pneumococcal polysaccharide vaccine compared with healthy subjects. A more favorable response is observed in patients treated with tumor necrosis factor-alpha-blocking agents compared with those treated with other immunosuppressive agents. Low systemic corticosteroid doses do not affect the responses to pneumococcal vaccines. Patients with human immunodeficiency virus and idiopathic pulmonary fibrosis receiving immunosuppressive therapy exhibit decreased immunogenicity to pneumococcal vaccines. The effects of T-cell-dependent PCV possibly depend on host memory B cells in some disease conditions. Several immunosuppressive therapy types and disease conditions may affect the responses to pneumococcal vaccines. Immunization should be administered before immunosuppressive medication initiation whenever possible.
MeSH term(s)	Autoimmune Diseases/immunology ; Chronic Disease ; Comorbidity ; Humans ; Immunogenicity, Vaccine ; Immunosuppressive Agents/pharmacology ; Pneumococcal Infections/prevention & control ; Pneumococcal Vaccines/immunology ; Respiratory Tract Diseases/immunology
Chemical Substances	Immunosuppressive Agents ; Pneumococcal Vaccines
Language	English
Publishing date	2019-01-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2664176-8
ISSN	2164-554X ; 2164-5515
ISSN (online)	2164-554X
ISSN	2164-5515
DOI	10.1080/21645515.2018.1564443
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Zs.A 6967: Show issues

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Article ; Online: Effect of niacin supplementation on nausea-like behaviour in an isoniazid-induced mouse model of pellagra.

Natsumi, Susai / Kuroita, Tomohiro / Ishikawa, Tatsuru / Kuronuma, Koji / Yoshioka, Takeshi

The British journal of nutrition

2021 Volume 127, Issue 7, Page(s) 961–971

Abstract: Niacin deficiency causes pellagra, the symptoms of which include dermatitis, diarrhoea and dementia. Investigating the mechanism underlying these phenotypes has been challenging due to the lack of an appropriate animal model. Here, we report a mouse ... ...

Abstract	Niacin deficiency causes pellagra, the symptoms of which include dermatitis, diarrhoea and dementia. Investigating the mechanism underlying these phenotypes has been challenging due to the lack of an appropriate animal model. Here, we report a mouse model of pellagra-related nausea induced by feeding mice a low-niacin diet and administering isoniazid (INH), which is thought to induce pellagra. Mice fed a normal or low-niacin diet received INH (0·3 or 1·0 mg/mg per animal, twice daily, 5 d), and nausea was evaluated based on pica behaviour, which considered the rodent equivalent of the emetic reflex. Furthermore, the effect of therapeutic niacin administration on nausea was evaluated in this model. Urinary and hepatic metabolite levels were analysed by LC coupled with MS. INH-induced pica was observed in mice fed a low-niacin diet but not in those fed a normal diet. Levels of urinary metabolites, such as 1-methyl-2-pyridone-5-carboxamide, kynurenic acid and xanthurenic acid, were significantly reduced in the mice treated with INH compared with those that did not receive INH. Furthermore, niacin supplementation prevented pica and restored the levels of some metabolites in this mouse model. Our findings suggest that INH-related nausea is pellagra-like. We also believe that our newly established method for quantifying pica is a useful tool for investigating the mechanisms of pellagra-related nausea.
MeSH term(s)	Animals ; Dietary Supplements ; Disease Models, Animal ; Isoniazid/adverse effects ; Mice ; Nausea/complications ; Niacin ; Pellagra/chemically induced ; Pellagra/diagnosis ; Pica/chemically induced ; Pica/complications
Chemical Substances	Niacin (2679MF687A) ; Isoniazid (V83O1VOZ8L)
Language	English
Publishing date	2021-06-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	280396-3
ISSN	1475-2662 ; 0007-1145
ISSN (online)	1475-2662
ISSN	0007-1145
DOI	10.1017/S0007114521001835
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