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Peer-reviewedCC BY-NCGut microbes

Schizophrenia-associated gut microbiota are linked to reduced colonic PRODH expression and behavioral changes in mice.

  • Keontae Park1
  • Min-Kyung Joo1
  • Im-Ho Lee1
  • Jeong-Hwa Woo1,2
  • Hee-Seo Park1,2,3
  • Chang Hyeon Kong1
  • Seo Yun Jung1
  • Soo-Yeon Woo1
  • Jae-Yoon Kim1
  • Hae Jeong Park4
  • Jong Woo Kim5
  • Dong-Hyun Kim1,2
2 more authors
  • Jong Hoon Ryu1,2,3
  • Jung-Hye Choi1,2,3
5 affiliations
  1. 1Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul, Korea.
  2. 2Neurobiota Research Center, Kyung Hee University, Seoul, Korea.
  3. 3Institute of Integrated Pharmaceutical Sciences, Kyung Hee University, Seoul, Korea.
  4. 4Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul, Korea.
  5. 5Department of Neuropsychiatry, School of Medicine, Kyung Hee University, Seoul, Korea.
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Abstract

Schizophrenia (SCZ) is a chronic neuropsychiatric disorder whose biological basis remains incompletely understood. Growing evidence implicates the gut-brain axis in SCZ, but the host pathways through which disease-associated microbiota may influence behavior remain unclear. Here, we examined whether the gut microbiota from patients with SCZ is associated with behavioral and metabolic alterations in male C57BL/6N mice. Fecal microbiota transplantation (FMT) from patients with SCZ was associated with impaired short-term recognition memory, reduced social novelty preference, and decreased prepulse inhibition in recipient mice. Transcriptomic profiling of colonic tissue identified reduced expression of Prodh, which encodes proline dehydrogenase (PRODH), together with elevated plasma proline levels. Comparative microbiome analyses identified a five-species candidate consortium associated with the SCZ donor microbiome - Escherichia fergusonii, Shigella sonnei, Morganella morganii, Citrobacter freundii, and Enterococcus faecalis. Oral administration of this five-species mixture (5-SM) was associated with similar behavioral changes, reduced colonic PRODH expression, and hyperprolinemia in mice. Together, these findings support a possible association between schizophrenia-associated changes in the gut microbiota, altered intestinal proline metabolism, and behavioral changes in mice.

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Cite

BibTeXRIS
BibTeX
@article{park2026schizophreniaassociated,
  title = {{Schizophrenia-associated gut microbiota are linked to reduced colonic PRODH expression and behavioral changes in mice.}},
  author = {Keontae Park and Min-Kyung Joo and Im-Ho Lee and Jeong-Hwa Woo and Hee-Seo Park and Chang Hyeon Kong and Seo Yun Jung and Soo-Yeon Woo and Jae-Yoon Kim and Hae Jeong Park and Jong Woo Kim and Dong-Hyun Kim and Jong Hoon Ryu and Jung-Hye Choi},
  journal = {Gut microbes},
  year = {2026},
  month = oct,
  doi = {10.1080/19490976.2026.2748081},
  url = {https://europepmc.org/article/MED/42886170},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Schizophrenia-associated gut microbiota are linked to reduced colonic PRODH expression and behavioral changes in mice.
AU  - Keontae Park
AU  - Min-Kyung Joo
AU  - Im-Ho Lee
AU  - Jeong-Hwa Woo
AU  - Hee-Seo Park
AU  - Chang Hyeon Kong
AU  - Seo Yun Jung
AU  - Soo-Yeon Woo
AU  - Jae-Yoon Kim
AU  - Hae Jeong Park
AU  - Jong Woo Kim
AU  - Dong-Hyun Kim
AU  - Jong Hoon Ryu
AU  - Jung-Hye Choi
PY  - 2026
DA  - 2026/10/16
JO  - Gut microbes
DO  - 10.1080/19490976.2026.2748081
UR  - https://europepmc.org/article/MED/42886170
AB  - Schizophrenia (SCZ) is a chronic neuropsychiatric disorder whose biological basis remains incompletely understood. Growing evidence implicates the gut-brain axis in SCZ, but the host pathways through which disease-associated microbiota may influence behavior remain unclear. Here, we examined whether the gut microbiota from patients with SCZ is associated with behavioral and metabolic alterations in male C57BL/6N mice. Fecal microbiota transplantation (FMT) from patients with SCZ was associated with impaired short-term recognition memory, reduced social novelty preference, and decreased prepulse inhibition in recipient mice. Transcriptomic profiling of colonic tissue identified reduced expression of Prodh, which encodes proline dehydrogenase (PRODH), together with elevated plasma proline levels. Comparative microbiome analyses identified a five-species candidate consortium associated with the SCZ donor microbiome - Escherichia fergusonii, Shigella sonnei, Morganella morganii, Citrobacter freundii, and Enterococcus faecalis. Oral administration of this five-species mixture (5-SM) was associated with similar behavioral changes, reduced colonic PRODH expression, and hyperprolinemia in mice. Together, these findings support a possible association between schizophrenia-associated changes in the gut microbiota, altered intestinal proline metabolism, and behavioral changes in mice.
SN  - 1949-0976
SN  - 1949-0984
ER  -