Intestinal Lysozyme liberates Nod1 ligands from microbes to direct insulin trafficking in pancreatic beta cells
Open accessAbstract
Long-range communication between intestinal symbiotic bacteria and extra-intestinal organs can occur through circulating bacterial signal molecules, through neural circuits, or through cytokines or hormones from host cells. Here we report that Nod1 ligands derived from intestinal bacteria act as signal molecules and directly modulate insulin trafficking in pancreatic beta cells. The cytosolic peptidoglycan receptor Nod1 and its downstream adapter Rip2 are required for insulin trafficking in beta cells in a cell-autonomous manner. Mechanistically, upon recognizing cognate ligands, Nod1 and Rip2 localize to insulin vesicles, recruiting Rab1a to direct insulin trafficking through the cytoplasm. Importantly, intestinal lysozyme liberates Nod1 ligands into the circulation, thus enabling long-range communication between intestinal microbes and islets. The intestine-islet crosstalk bridged by Nod1 ligands modulates host glucose tolerance. Our study defines a new type of inter-organ communication based on circulating bacterial signal molecules, which has broad implications for understanding the mutualistic relationship between microbes and host.
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The presence of circulating Nod1 ligand depends on lysozyme in the intestinal lumen, and deficiency of Lyz1 in mice leads to reduced level of microbial Nod1 ligand in the circulation.
“We previously reported that the presence of circulating Nod1 ligand depends on lysozyme in the intestinal lumen, and deficiency of Lyz1 in mice leads to reduced level of microbial Nod1 ligand in the circulation (Zhang et al., 2019).”
From Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells (2021) · cites this paper as Zhang et al., 2019
Nod1 ligand derived from intestinal microbes gets into the circulation and modulates a range of biological activities in a Nod1-dependent manner.
“Nod1 ligand derived from intestinal microbes is known to get into the circulation and modulate a range of biological activities in a Nod1-dependent manner (Bouskra et al., 2008; Chan et al., 2017; Zhang et al., 2019; Hergott et al., 2016; Iwamura et al., 2017).”
From Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells (2021) · cites this paper as Zhang et al., 2019
Previous studies showed enhanced membrane recruitment of Nod1 and Nod2 upon commensal bacterial colonization in β cells and intestinal Paneth cells, respectively.
“Indeed, our previous studies have shown enhanced membrane recruitment of Nod1 and Nod2 upon commensal bacterial colonization in β cells and intestinal Paneth cells, respectively (Zhang et al., 2019).”
From Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells (2021) · cites this paper as Zhang et al., 2019
Nod1 sensing regulates 5-HT signaling in intestinal epithelium and regulates insulin trafficking in islet beta cells.
“Beyond immunity and inflammation, Nod1 sensing regulates 5-HT signaling in intestinal epithelium and regulates insulin trafficking in islet beta cells (Pusceddu et al., 2019; Zhang et al., 2019).”
From Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells (2021) · cites this paper as Zhang et al., 2019
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References 63 · Cited by 73
- Authors
- Zhang, Q., Pan, Y., Zeng, B., Zheng, X., Wang, H., Shen, X., Li, H., Jiang, Q., Zhao, J., Meng, Z.-X., Li, P., Chen, Z., Wei, H., & Liu, Z.
- Affiliations
- Chinese Academy of Sciences (CN)
- Army Medical University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Zhejiang University (CN)
- Sun Yat-sen University (CN)
- Corresponding author
- Wei, Hong
- Liu, Zhihua
- ORCID
- Venue
- Cell Research
- Published
- 2019-06-14
- Volume
- 29
- Issue
- 7
- Pages
- 516-532
- ISSN
- 1001-0602 (ISSN-L)
- 1748-7838
- PMC
- PMC6796897
- OpenAlex
- W2952289250
- Cited by
- 73
- References
- 63
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 14 · 2023: 12 · 2022: 9 · 2021: 10 · 2020: 6 · 2019: 5
- FWCI
- 7.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Cell Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81670482, 81370906)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- NOD1, RIP2, pancreatic beta cells, Rab1A, peptidoglycan, glucose tolerance, gut microbiota, inter-organ communication, host-microbe mutualism
- MeSH terms
- Animals, Female, Humans, Insulin, Intestines, Ligands, Male, Mice, Inbred C57BL, Muramidase, Lactococcus lactis, Mice, Inbred NOD, Lactiplantibacillus plantarum, Insulin-Secreting Cells, Mice, Nod1 Signaling Adaptor Protein, Receptor-Interacting Protein Serine-Threonine Kinase 2, HEK293 Cells
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