ORIGINAL RESEARCH article
Front. Immunol.
Sec. Microbial Immunology
This article is part of the Research TopicHost and Microbe Immunometabolic Chat: A New Era of Organismal CommunicationView all 10 articles
Restoration of Peripheral ILC3s by Washed Microbiota Transplantation Improves Lipid Profiles in Hyperlipidemia Patients
Provisionally accepted
- 1The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
- 2Southern Medical University Nanfang Hospital, Guangzhou, China
- 3Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China
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Background: The contribution of circulating group 3 innate lymphoid cells (ILC3s) to lipid dysregulation has remained poorly defined, and the mechanisms through which washed microbiota transplantation (WMT) improves lipid metabolism require further clarification. Methods: Peripheral ILC subsets and plasma IL-22 were assessed in hyperlipidemia patients and healthy controls. The lipid-lowering effects of WMT were evaluated in a prospective cohort without lipid-lowering medications. Gut microbial and plasma metabolite profiles before and after WMT were analyzed. A hyperlipidemic mouse model was used to determine whether healthy microbiota promote hepatic ILC3 homing via integrin α4. Results: Hyperlipidemia was characterized by reduced circulating ILC3s, integrin α4+ ILC3s, and plasma IL-22, all of which showed inverse correlations with TC, TG, LDL-C, non-HDL-C, and ApoB. Significant lipid improvements were achieved after WMT, accompanied by increased circulating ILC3s and integrin α4+ ILC3s, paralleling reductions in TC and LDL-C. WMT induced marked remodeling of gut microbiota and plasma metabolites, including taxa and metabolites positively associated with ILC3 restoration and lipid improvement. In hyperlipidemic mice, healthy microbiota transplantation increased hepatic ILC3 and integrin α4+ ILC3 accumulation and improved lipid levels, whereas integrin α4 blockade impaired ILC3 liver homing and attenuated the metabolic benefit. Conclusion: Hyperlipidemia is associated with depletion of circulating ILC3s and reduced IL-22. Restoration of ILC3 subsets and enhancement of integrin α4–dependent hepatic homing are achieved after WMT, accompanying improvements in lipid metabolism.
Keywords: Hyperlipidemia, Group 3 Innate lymphoid cells, washed microbiota transplantation, Lipid Metabolism, Immunometabolism
Received: 18 Aug 2025; Accepted: 20 Nov 2025.
Copyright: © 2025 Wei, Wang, Song, Wang, He and Zhong. 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:
Hao Wang, mr_whouse@163.com
Xing-Xiang He, hexingxiang@gdpu.edu.cn
Hao-Jie Zhong, jaxzhong@126.com
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