Evidence map›Paper›PMID 38093299›Full record

ArticleBMC pharmacology & toxicology2023

Host microbiome associated low intestinal acetate correlates with progressive NLRP3-dependent hepatic-immunotoxicity in early life microcystin-LR exposure.

Madhura More, Somdatta Chatterjee, Punnag Saha, Dipro Bose, Ayushi Trivedi, Subhajit Roy, Saurabh Chatterjee

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC pharmacology & toxicology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 29% of its field
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

3 citing papers in PubMed, 2 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
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 at 4 institutions in 1 country.

Madhura MoreEnvironmental Health and Disease Laboratory, Department of Environmental and Occupational Health, Program in Public Health, University of California - Irvine, 92697, Irvine, CA, USA.
Somdatta ChatterjeeIGeneX Inc-Reference Laboratory, 95035, Miltipas, CA, USA.
Punnag SahaEnvironmental Health and Disease Laboratory, Department of Environmental and Occupational Health, Program in Public Health, University of California - Irvine, 92697, Irvine, CA, USA.
Dipro BoseEnvironmental Health and Disease Laboratory, Department of Environmental and Occupational Health, Program in Public Health, University of California - Irvine, 92697, Irvine, CA, USA.
Ayushi TrivediEnvironmental Health and Disease Laboratory, Department of Environmental and Occupational Health, Program in Public Health, University of California - Irvine, 92697, Irvine, CA, USA.
Subhajit RoyEnvironmental Health and Disease Laboratory, Department of Environmental and Occupational Health, Program in Public Health, University of California - Irvine, 92697, Irvine, CA, USA.
Saurabh ChatterjeeEnvironmental Health and Disease Laboratory, Department of Environmental and Occupational Health, Program in Public Health, University of California - Irvine, 92697, Irvine, CA, USA. saurabhc@hs.uci.edu.
University of California, Irvine · USIrvine University · USTraining Programs in Epidemiology and Public Health Interventions Network · USUC Irvine Health · US

Funding

The effects of climate change on the natural attenuation and sedimentary record of harmful algal bloom toxins and microbial signalsP01ES028942 · NIEHS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI CHATTERJEE, SAURABH · 2018 to 2022
$5.7M
NIEHS NIH HHS 1P01ES028942-01#Project 4NIEHS NIH HHS P01 ES028942
6 · The paper itself

Abstract

backgroundMicrocystins (MCs), potent hepatotoxins pose a significant health risk to humans, particularly children, who are more vulnerable due to higher water intake and increased exposure during recreational activities.

methodsHere, we investigated the role of host microbiome-linked acetate in modulating inflammation caused by early-life exposure to the cyanotoxin Microcystin-LR (MC-LR) in a juvenile mice model.

resultsOur study revealed that early-life MC-LR exposure disrupted the gut microbiome, leading to a depletion of key acetate-producing bacteria and decreased luminal acetate concentration. Consequently, the dysbiosis hindered the establishment of a gut homeostatic microenvironment and disrupted gut barrier function. The NOD-like receptor family pyrin domain - containing 3 (NLRP3) inflammasome, a key player in MC-induced hepatoxicity emerged as a central player in this process, with acetate supplementation effectively preventing NLRP3 inflammasome activation, attenuating hepatic inflammation, and decreasing pro-inflammatory cytokine production. To elucidate the mechanism underlying the association between early-life MC-LR exposure and the progression of metabolic dysfunction associated steatotic liver disease (MASLD), we investigated the role of acetate binding to its receptor -G-protein coupled receptor 43 (GPR43) on NLRP3 inflammasome activation. Our results demonstrated that acetate-GPR43 signaling was crucial for decreasing NLRP3 protein levels and inhibiting NLRP3 inflammasome assembly. Further, acetate-induced decrease in NLRP3 protein levels was likely mediated through proteasomal degradation rather than autophagy. Overall, our findings underscore the significance of a healthy gut microbiome and its metabolites, particularly acetate, in the progression of hepatotoxicity induced by early life toxin exposure, crucial for MASLD progression.

conclusionsThis study highlights potential therapeutic targets in gut dysbiosis and NLRP3 inflammasome activation for mitigating toxin-associated inflammatory liver diseases.

Indexed as

Gastrointestinal MicrobiomeNLR Family, Pyrin Domain-Containing 3 ProteinAcetatesAnimalsDysbiosisInflammasomesInflammationMarine ToxinsMiceMicrocystinsAcetatescyanoginosin LRInflammasomesMarine ToxinsMicrocystinsNLR Family, Pyrin Domain-Containing 3 ProteinAcetateGPR43MicrobiomeMicrocystinNLRP3

Identifiers

PMID38093299
PMCPMC10720243
OpenAlexW4389685663

What Socratic holds

Textmetadata
LicenceCC BY
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.