Evidence map›Paper›PMID 41974884›Full record

ReviewMolecular psychiatry2026

Pleiotropic modulation of the gut-brain-lung axis by ketamine and its enantiomers.

Xin Zhao, Xinyu Zhang, Shiying Yuan, Kenji Hashimoto, Jiancheng Zhang

Abstract readReview
In one paragraph

Review in Molecular psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Xin Zhao *Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, P. R. China.
Xinyu Zhang *Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, P. R. China.ORCID http://orcid.org/0009-0005-3138-681X
Shiying YuanDepartment of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, P. R. China. yuan_shiying@163.com.ORCID http://orcid.org/0000-0002-6415-1604
Kenji HashimotoChiba University Center for Forensic Mental Health, Chiba, 260-8670, Japan. hashimoto@faculty.chiba-u.jp.ORCID http://orcid.org/0000-0002-8892-0439
Jiancheng ZhangDepartment of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, P. R. China. zhjcheng1@126.com.ORCID http://orcid.org/0000-0002-2820-0851

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82272231National Natural Science Foundation of China (National Science Foundation of China) 82472223
6 · The paper itself

Abstract

Ketamine, a potent N-methyl-D-aspartate receptor (NMDAR) antagonist, is widely used for anesthesia and analgesia and, because of its rapid antidepressant effects, in psychiatry. Increasing evidence suggests that ketamine and its enantiomers-(R)-ketamine (arketamine) and (S)-ketamine (esketamine)-also modulate systemic immunity and provide organ protection, partly through interactions with the gut microbiota, microbial metabolites, and intestinal immune-cell trafficking. However, these gut-mediated pathways must be distinguished from ketamine's well-established direct central and peripheral actions. In this review, we summarize how ketamine engages the gut-brain and gut-lung axes, emphasizing anti-inflammatory, immunoregulatory, and barrier-protective effects, while critically evaluating the evidence for causality in gut-organ communication. Along the gut-brain axis, ketamine is associated with restoration of microbial balance, normalization of short-chain fatty acid levels, and reduced migration of gut-derived γδ T17 and Th17 cells to the central nervous system, correlating with attenuated neuroinflammation and depressive-like behaviors. Through the gut-lung axis, ketamine has been reported to limit bacterial translocation and mesenteric lymph-associated inflammatory signaling and reduces pulmonary infiltration of pro-inflammatory cells, suggesting potential relevance in acute lung injury and other respiratory disorders. We also discuss enantiomer-specific effects: arketamine appears to provide more sustained neuroprotection and may be associated with fewer adverse effects than esketamine. Overall, these findings suggest the broad therapeutic potential of ketamine and its enantiomers for neuropsychiatric and inflammatory diseases, while underscoring the need for careful evaluation of long-term safety, optimal dosing, microbiota-targeted adjunctive strategies, and causal studies to distinguish direct pharmacological actions from indirect, microbiota-mediated effects.

Indexed as

Brain-Gut AxisKetamineAnimalsBrainGastrointestinal MicrobiomeHumansLungReceptors, N-Methyl-D-AspartateStereoisomerismKetamineReceptors, N-Methyl-D-Aspartate

Identifiers

PMID41974884
PMCPMC13441983

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.