The bacterial peptidoglycan-sensing molecule Pglyrp2 modulates brain development and behavior
Open accessAbstract
Recent studies have revealed that the gut microbiota modulates brain development and behavior, but the underlying mechanisms are still poorly understood. Here, we show that bacterial peptidoglycan (PGN) derived from the commensal gut microbiota can be translocated into the brain and sensed by specific pattern-recognition receptors (PRRs) of the innate immune system. Using expression-profiling techniques, we demonstrate that two families of PRRs that specifically detect PGN (that is, PGN-recognition proteins and NOD-like receptors), and the PGN transporter PepT1 are highly expressed in the developing brain during specific windows of postnatal development in both males and females. Moreover, we show that the expression of several PGN-sensing molecules and PepT1 in the developing striatum is sensitive to manipulations of the gut microbiota (that is, germ-free conditions and antibiotic treatment). Finally, we used the PGN-recognition protein 2 (Pglyrp2) knockout mice to examine the potential influence of PGN-sensing molecules on brain development and behavior. We demonstrate that the absence of Pglyrp2 leads to alterations in the expression of the autism risk gene c-Met, and sex-dependent changes in social behavior, similar to mice with manipulated microbiota. These findings suggest that the central activation of PRRs by microbial products could be one of the signaling pathways mediating the communication between the gut microbiota and the developing brain.
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Peptidoglycan may directly impact neuronal function.
“These findings suggest that PGN may directly impact neuronal function [83,84].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [83]
Treatment with antibiotics has been used to deplete microbial ligands in the circulation.
“Treatment with antibiotics has been used to deplete microbial ligands in the circulation (Clarke et al., 2010; Bird, 2010; Arentsen et al., 2017; Hergott et al., 2016).”
From Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells (2021) · cites this paper as Arentsen et al., 2017
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Self-citation
- Authors
- Arentsen, T., Qian, Y., Gkotzis, S., Femenia, T., Wang, T., Udekwu, K., Forssberg, H., & Diaz Heijtz, R.
- Affiliations
- Karolinska Institutet (SE)
- Stockholm University (SE)
- Venue
- Molecular Psychiatry
- Published
- 2016-11-15
- Volume
- 22
- Issue
- 2
- Pages
- 257-266
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC5285465
- OpenAlex
- W2551810737
- Cited by
- 280
- References
- 54
- Citations by year
- 2026: 7 · 2025: 32 · 2024: 35 · 2023: 38 · 2022: 26 · 2021: 36 · 2020: 38 · 2019: 28 · 2018: 21 · 2017: 18 · 2016: 1
- FWCI
- 11.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Psychiatry (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Karolinska Institutet
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet (2012-03564, K2015-62X-22745-01-4, 621-2012-3564)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- bacterial peptidoglycan, gut microbiota, brain development, behavior, NOD-like receptors, PepT1, pattern recognition receptors, germ-free mice, antibiotic therapy, c-Met, autism risk genes, social behavior, sex differences, striatum, microbiota-gut-brain axis
- MeSH terms
- Gastrointestinal Microbiome, Animals, Brain, Carrier Proteins, Female, Immunity, Innate, Male, N-Acetylmuramoyl-L-alanine Amidase, Peptidoglycan, Signal Transduction, Mice, Knockout, Mice
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