. 2023 Nov 30;15(1):59.

doi: 10.1186/s13099-023-00587-4.

Elevated plasma and bile levels of corisin, a microbiota-derived proapoptotic peptide, in patients with severe acute cholangitis

Ryo Nishiwaki^{1

2}, Ichiro Imoto¹, Satoko Oka³, Taro Yasuma^{4

5}, Hajime Fujimoto^{4

6}, Corina N D'Alessandro-Gabazza^{7

5}, Masaaki Toda⁵, Tetsu Kobayashi^{4

6}, Hataji Osamu⁸, Kodai Fujibe⁹, Kenichiro Nishikawa⁹, Tetsuya Hamaguchi², Natsuko Sugimasa², Midori Noji², Yoshiyuki Ito², Kenji Takeuchi², Isaac Cann^{7

10

11}, Yasuhiro Inoue², Toshio Kato², Esteban C Gabazza^{12

13

14}

Affiliations

¹ Digestive Endoscopy Center, Doshinkai Tohyama Hospital, Minamishinmachi 17-22, Tsu, Mie, 514-0043, Japan.
² Department of Surgery, Doshinkai Tohyama Hospital, Minamishinmachi 17-22, Tsu, Mie, 514-0043, Japan.
³ Department of Internal Medicine, Doshinkai Tohyama Hospital, Minamishinmachi 17-22, Tsu, Mie, 514-0043, Japan.
⁴ Microbiome Research Center, Mie University, Edobashi 2-174, Tsu, Mie, 514-8507, Japan.
⁵ Department of Immunology, Mie University Faculty and Graduate School of Medicine, Mie University Hospital, Edobashi 2-174, Tsu, Mie, 514-8507, Japan.
⁶ Department of Pulmonary and Critical Care Medicine, Mie University Faculty and Graduate School of Medicine, Mie University Hospital, Edobashi 2-174, Tsu, Mie, 514-8507, Japan.
⁷ Carl R. Woese Institute for Genomic Biology (Microbiome Metabolic Engineering), University of IL at Urbana-Champaign, Urbana, IL, USA.
⁸ Respiratory Center, Matsusaka Municipal Hospital, Tonomachi1550, Matsusaka, Mie, 515-8544, Japan.
⁹ Department of Gastroenterology, Matsusaka Municipal Hospital, Tonomachi1550, Matsusaka, Mie, 515-8544, Japan.
¹⁰ Department of Microbiology, The University of IL at Urbana-Champaign, Urbana, IL, USA.
¹¹ Department of Animal Science, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA.
¹² Microbiome Research Center, Mie University, Edobashi 2-174, Tsu, Mie, 514-8507, Japan. gabazza@doc.medic.mie-u.ac.jp.
¹³ Carl R. Woese Institute for Genomic Biology (Microbiome Metabolic Engineering), University of IL at Urbana-Champaign, Urbana, IL, USA. gabazza@doc.medic.mie-u.ac.jp.
¹⁴ Department of Immunology, Mie University Faculty and Graduate School of Medicine, Mie University Hospital, Edobashi 2-174, Tsu, Mie, 514-8507, Japan. gabazza@doc.medic.mie-u.ac.jp.

PMID: 38037145
PMCID: PMC10688013
DOI: 10.1186/s13099-023-00587-4

Elevated plasma and bile levels of corisin, a microbiota-derived proapoptotic peptide, in patients with severe acute cholangitis

Ryo Nishiwaki et al. Gut Pathog. 2023.

. 2023 Nov 30;15(1):59.

doi: 10.1186/s13099-023-00587-4.

Authors

Affiliations

¹ Digestive Endoscopy Center, Doshinkai Tohyama Hospital, Minamishinmachi 17-22, Tsu, Mie, 514-0043, Japan.
² Department of Surgery, Doshinkai Tohyama Hospital, Minamishinmachi 17-22, Tsu, Mie, 514-0043, Japan.
³ Department of Internal Medicine, Doshinkai Tohyama Hospital, Minamishinmachi 17-22, Tsu, Mie, 514-0043, Japan.
⁴ Microbiome Research Center, Mie University, Edobashi 2-174, Tsu, Mie, 514-8507, Japan.
⁵ Department of Immunology, Mie University Faculty and Graduate School of Medicine, Mie University Hospital, Edobashi 2-174, Tsu, Mie, 514-8507, Japan.
⁶ Department of Pulmonary and Critical Care Medicine, Mie University Faculty and Graduate School of Medicine, Mie University Hospital, Edobashi 2-174, Tsu, Mie, 514-8507, Japan.
⁷ Carl R. Woese Institute for Genomic Biology (Microbiome Metabolic Engineering), University of IL at Urbana-Champaign, Urbana, IL, USA.
⁸ Respiratory Center, Matsusaka Municipal Hospital, Tonomachi1550, Matsusaka, Mie, 515-8544, Japan.
⁹ Department of Gastroenterology, Matsusaka Municipal Hospital, Tonomachi1550, Matsusaka, Mie, 515-8544, Japan.
¹⁰ Department of Microbiology, The University of IL at Urbana-Champaign, Urbana, IL, USA.
¹¹ Department of Animal Science, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA.
¹² Microbiome Research Center, Mie University, Edobashi 2-174, Tsu, Mie, 514-8507, Japan. gabazza@doc.medic.mie-u.ac.jp.
¹³ Carl R. Woese Institute for Genomic Biology (Microbiome Metabolic Engineering), University of IL at Urbana-Champaign, Urbana, IL, USA. gabazza@doc.medic.mie-u.ac.jp.
¹⁴ Department of Immunology, Mie University Faculty and Graduate School of Medicine, Mie University Hospital, Edobashi 2-174, Tsu, Mie, 514-8507, Japan. gabazza@doc.medic.mie-u.ac.jp.

PMID: 38037145
PMCID: PMC10688013
DOI: 10.1186/s13099-023-00587-4

Abstract

Background: Acute cholangitis is a severe, life-threatening infection of the biliary system that requires early diagnosis and treatment. The Tokyo Guidelines recommend a combination of clinical, laboratory, and imaging findings for diagnosis and severity assessment, but there are still challenges in identifying severe cases that need immediate intervention. The microbiota and its derived products have been implicated in the pathogenesis of acute cholangitis. Corisin is a microbiome-derived peptide that induces cell apoptosis, acute tissue injury, and inflammation. This study aimed to evaluate the potential of plasma and bile corisin as a biomarker of acute cholangitis.

Methods: Forty patients with acute cholangitis associated with choledocholithiasis or malignant disease were enrolled. Nine patients without acute cholangitis were used as controls. Corisin was measured by enzyme immunoassays in plasma and bile samples. Patients were classified into severe and non-severe groups. The associations of plasma and bile corisin with the clinical grade of acute cholangitis and other parameters were analyzed by univariate and multivariate regression analysis.

Results: Plasma and bile corisin levels were significantly higher in patients with acute cholangitis than in controls. Patients with severe acute cholangitis had significantly higher plasma and bile corisin levels than those with non-severe form of the disease. Bile corisin level was significantly correlated with markers of inflammation, coagulation, fibrinolysis, and renal function. Univariate analysis revealed a significant association of bile corisin but a weak association of plasma corisin with the clinical grade of acute cholangitis. In contrast, multivariate analysis showed a significant relationship between plasma corisin level and the disease clinical grade. The receiver operating characteristic curve analysis showed low sensitivity but high specificity for plasma and bile corisin to detect the severity of acute cholangitis. The plasma and bile corisin sensitivity was increased when serum C-reactive protein level was included in the receiver operating characteristic curve analysis.

Conclusions: Overall, these findings suggest that plasma and bile corisin levels may be useful biomarkers for diagnosing and monitoring acute cholangitis and that corisin may play a role in the pathophysiology of the disease by modulating inflammatory, coagulation and renal pathways.

Keywords: Acute cholangitis; Apoptosis; Choledocholithiasis; Corisin; Dysbiosis; Microbiota.

PubMed Disclaimer

Conflict of interest statement

E.C.G. and T.Y. received a Research Grant from Takeda Foundation. None of the other authors declared any competing interest regarding the data reported in this manuscript.

Figures

**Fig. 1**
Flow chart for patients’ selection. Eighty-two patients with obstructive biliary disease underwent endoscopic retrograde cholangiopancreatography. Of these, 49 patients were included in the study

**Fig. 2**
Phylum abundance and Shannon diversity. Microbial composition analysis (A) and microbial diversity (B) assessment were performed as described under Materials and Methods. *p < 0.05. Non-AC, non-acute cholangitis patients; AC, acute cholangitis patients

**Fig. 3**
Increased levels of plasma and bile corisin in patients with acute cholangitis. Corisin was measured by enzyme immunoassays. There were 40 patients with acute cholangitis and 9 without acute cholangitis. Data are expressed as the mean ± SEM. Statistical analysis was performed by the Mann–Whitney U test. AC, acute cholangitis. *p < 0.05; **p < 0.01

**Fig. 4**
Increased levels of plasma and bile corisin in patients with severe acute cholangitis. Corisin was measured by enzyme immunoassays. There were 9 patients with non-cholangitis, 30 with non-severe (mild disease 18 cases + moderate disease 12 cases) acute cholangitis, and 10 with severe disease. Data are expressed as the mean ± SEM. Statistical analysis was performed by ANOVA Fisher’s predicted least significant difference test. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001

**Fig. 5**
Significant correlation of bile corisin with inflammatory, coagulation, fibrinolysis, and renal function markers. Corisin was measured by enzyme immunoassays. Patients with (n = 40) and without (n = 9) acute cholangitis were included to evaluate the correlation. Statistical analysis was performed by Spearman correlation

**Fig. 6**
Receiver operating characteristic (ROC) curve analysis for the diagnosis of severe acute cholangitis. The ROC curves of serum C-reactive protein (CRP), plasma corisin, and bile corisin (A) or their combination (B) were plotted to evaluate their diagnostic performance. AUC, area under the curve

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Elevated plasma and bile levels of corisin, a microbiota-derived proapoptotic peptide, in patients with severe acute cholangitis

Affiliations

Elevated plasma and bile levels of corisin, a microbiota-derived proapoptotic peptide, in patients with severe acute cholangitis

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Abstract

Conflict of interest statement

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