ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Molecular Viral Pathogenesis
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1643636
This article is part of the Research TopicCytokine Signaling and Innate Host Defense in Modulation of Viral Infections and The Viral EvasionView all 8 articles
Tryptophan Metabolic Reprogramming Modulates Cytokine Networks in nucleos(t)ide analogue-treated chronic Hepatitis B patients
Provisionally accepted
- Sichuan University West China Hospital Department of Laboratory Medicine, Chengdu, China
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Background & Aims: Hepatitis B virus (HBV) infection remains a global health challenge. Tryptophan metabolism influences immune regulation, but its interplay with cytokines during antiviral therapy is unclear. We investigated associations between tryptophan pathways and cytokine profiles in the chronic hepatitis B (CHB) patients with varying treatment outcomes.Methods: This retrospective study included 106 CHB patients (including 29 functional cure cases) receiving nucleos(t)ide analogues (NAs) and 29 healthy controls. Plasma levels of 20 tryptophan metabolites (kynurenine, serotonin, and bacterial pathways) were quantified by HPLC-MS/MS, and 12 cytokines were measured via flow cytometry. Multivariate analyses were performed.Results: Functional cure patients showed unique metabolic patterns. Indole-3-carboxaldehyde (IAld) levels increased progressively from HBsAg positive groups (HBeAg-: 63.324 nmol/L; HBeAg+: 65.938 nmol/L) to functional cure (91.44 nmol/L) and healthy controls (130.634 nmol/L) (P < 0.01), exhibiting negative correlations with HBsAg (r = -0.31) and IFN-γ (r = -0.53) but positive correlation with IL-1β (r = 0.47). Picolinic acid (PA) was significantly elevated in the functional cure group (P<0.001), associated with reduced HBsAg, IL-12 and increased IL-1β, IL-10 levels, indicating potential antiviral effects. Serotonin (5-HT) levels were higher in cured patients and correlated with IL-1β and IFN-α (P < 0.05). HBeAg-positive patients displayed increased kynurenine-to-tryptophan (Kyn/Trp) ratios (P < 0.05), while non-cured patients showed metabolic blockade downstream of 3hydroxykynurenine (elevated 3-HK/Kyn ratios and reduced KA, XA/3-HK, 3-HAA/3-HK, and NAA levels; P < 0.05).The tryptophan metabolites (IAld, PA, 5-HT) were found to correlate with cytokine levels (IL-1β, IL-10), potentially implicating their involvement in immune regulation and antiviral responses. These observations delineate a metabolic-immune framework that may inform future therapeutic development for HBV.
Keywords: tryptophan metabolism1, cytokine profiles2, chronic hepatitis B3, bacterial degradation pathway4, functional cure5, Indole-3-carboxaldehyde6, picolinic acid7, 5-hydroxytryptamine8
Received: 09 Jun 2025; Accepted: 08 Jul 2025.
Copyright: © 2025 Gao, Wu, Li, Dai and CAI. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xinhua Dai, Sichuan University West China Hospital Department of Laboratory Medicine, Chengdu, China
BEI CAI, Sichuan University West China Hospital Department of Laboratory Medicine, Chengdu, China
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