ORIGINAL RESEARCH article
Front. Immunol.
Sec. Mucosal Immunity
This article is part of the Research TopicHost-microbiota immuno-interactions for personalized microbial therapeutics: Volume IIView all 7 articles
Akkermansia muciniphila primes lung-resident antiviral immunity via the gut–lung axis during SARS-CoV-2 infection
Provisionally accepted
Gi Cheon Kim1
Jun-Soo Do1
Sung-Hee Kim1
Jong-Hwi Yoon1
Jiseon Kim1
Donghun Jeon1
Emmanuel Hitayezu2Intan Rizki Mauliasari2
Naeok Koo1
Jeong Jin Kim1
Jun-Young Seo1Subin Lee1Siyoon Kim1
Ki Taek Nam1*
Kwang Hyun Cha1*
Ho-Keun Kwon1*
Je Kyung Seong3*- 1College of Medicine, Yonsei University, Seoul, Republic of Korea
- 2Korea Institute of Science and Technology, Seongbuk-gu, Republic of Korea
- 3Seoul National University, Gwanak-gu, Republic of Korea
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The gut microbiota plays a pivotal role in shaping systemic immunity and modulating the gut– lung axis, both critical during respiratory infections such as COVID-19. Although SARS-CoV-2 infection is known to disrupt gut microbial composition, the downstream consequences on microbial functionality and host immunity remain poorly characterized. In this study, we utilized K18-hACE2 transgenic mice infected with SARS-CoV-2 variants WA and Omicron to investigate how gut microbial shifts influence respiratory immunity, focusing on the immunoregulatory role of Akkermansia muciniphila. SARS-CoV-2 infection reduced microbial diversity and led to consistent enrichment of A. muciniphila, along with disruptions in glycosaminoglycan degradation and lipid metabolism pathways. Remarkably, prophylactic administration of live A. muciniphila significantly ameliorated virus-induced weight loss, improved lung histopathology, and enhanced local antiviral immune responses without exacerbating systemic inflammation. Treated animals exhibited increased Th2 and Th17 cytokines, robust expansion of tissue-resident memory T cells, and formation of inducible bronchus-associated lymphoid tissue (iBALT), hallmark features of potentiated mucosal immunity. Collectively, these results identify A. muciniphila as a key marker of COVID-19-associated gut dysbiosis and a promising live biotherapeutic candidate for enhancing mucosal defense against respiratory viral infections through modulation of the gut–lung axis.
Keywords: Akkermansia muciniphila, Gut-Lung Axis, Inducible bronchus-associated lymphoid tissue (iBALT), SARS-CoV2 (COVID- 19), tissue resident memory T cells (TRM)
Received: 08 Dec 2025; Accepted: 23 Jan 2026.
Copyright: © 2026 Kim, Do, Kim, Yoon, Kim, Jeon, Hitayezu, Mauliasari, Koo, Kim, Seo, Lee, Kim, Nam, Cha, Kwon and Seong. 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:
Ki Taek Nam
Kwang Hyun Cha
Ho-Keun Kwon
Je Kyung Seong
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