Evidence map›Paper›PMID 41031863›Full record

ArticleAnnals of the New York Academy of Sciences2025

Gut Microbiota-Derived Lipopolysaccharides and Short-Chain Fatty Acids Regulate Immune Responses via FFAR2/FFAR3 in Lung Ischemia-Reperfusion Injury.

Daisuke Maruyama, Thien N M Doan, Xiaoli Tian, Tomohiro Chaki, Jade J Yeh, Brian T Layden, Arun Prakash

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of the New York Academy of Sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Review
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

7 authors.

Daisuke MaruyamaDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0001-5285-9309
Thien N M DoanDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Xiaoli TianDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Tomohiro ChakiDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Jade J YehDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois Chicago, Chicago, Illinois, USA.
Brian T LaydenDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois Chicago, Chicago, Illinois, USA.
Arun PrakashDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.

Funding

Comprehensive Anesthesia Research TrainingT32GM008440 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1996 to 2025
$1.4M
The Gut-Lung Axis: Immunometabolism Linking the Gut Microbiome and Lung ImunityR01HL146753 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Arun Prakash Budde · 2022 to 2023
$1.1M
NHLBI NIH HHS 1R01HL146753NHLBI NIH HHS R01 HL146753NIGMS NIH HHS T32 GM008440NIH HHS T32-GM008440UCSF BCMM Trainee Pilot Award 7030928-A73H5UCSF NORC P30DK098722
6 · The paper itself

Abstract

Lung ischemia-reperfusion (IR) injury is a sterile inflammatory process seen in conditions such as hemorrhage-resuscitation and pulmonary embolism. Our previous work suggests that alveolar macrophages (AMs) drive the inflammatory cascade via NLRP3 inflammasome activation, and that gut-derived lipopolysaccharides (LPS) and short-chain fatty acids (SCFAs) influence these responses. However, the precise mechanisms by which gut microbiota signals govern AM function during lung IR remain unclear. Here, we show that germ-free mice exhibit reduced inflammatory responses compared to specific pathogen-free mice following lung IR injury in vivo. In contrast, mice lacking free fatty acid receptor (FFAR)2 or FFAR3-receptors for SCFAs-display heightened inflammation relative to wild-type controls. Ex vivo and in vitro nutritional IR experiments further demonstrate that AMs, primed with LPS, produce IL-1β via NLRP3 inflammasome and caspase-1 activation. Notably, SCFAs significantly diminish IR-induced IL-1β release, indicating a protective effect. These findings support a gut-lung axis in which gut microbiota modulate baseline lung immune capacity or lung immune tone through the transmission of LPS and SCFAs, thereby shaping the lung's response to sterile injury. Gut microbiota-based therapies, including dietary fiber interventions, may thus represent a promising therapeutic strategy for regulating inflammatory processes in the lung.

Indexed as

Fatty Acids, VolatileGastrointestinal MicrobiomeLipopolysaccharidesLung InjuryReceptors, G-Protein-CoupledReperfusion InjuryAnimalsInflammasomesInterleukin-1betaLungMacrophages, AlveolarMaleMiceMice, Inbred C57BLMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteinFatty Acids, VolatileFfar2 protein, mouseFFAR3 protein, mouseInflammasomesInterleukin-1betaLipopolysaccharidesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseReceptors, G-Protein-CoupledFFARgut–lung axisischemia–reperfusion injuryLPSshort‐chain fatty acid (SCFA)

Identifiers

PMID41031863
PMCPMC12987534

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 Socratic graph.