Evidence mapPaperPMID 40638708Full record

ArticlePloS one2025

Dual effects of indoxyl sulfate on modulation of human hepatic CYP3A activity, with individual differences.

Masao Togao, Naoyuki Asakawa, Gaku Wagai, Yuki Ohta-Takada, Jun Otsuka, Minoru Ando, Akinobu Kurita, Koji Kawakami

Abstract read
In one paragraph

Article in PloS one, 2025. 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

8 authors.

Masao TogaoSafety Research Department, Yakult Central Institute, Kunitachi-shi, Tokyo, Japan.ORCID https://orcid.org/0000-0003-1468-9075
Naoyuki AsakawaSafety Research Department, Yakult Central Institute, Kunitachi-shi, Tokyo, Japan.
Gaku WagaiSafety Research Department, Yakult Central Institute, Kunitachi-shi, Tokyo, Japan.
Yuki Ohta-TakadaSafety Research Department, Yakult Central Institute, Kunitachi-shi, Tokyo, Japan.
Jun OtsukaSafety Research Department, Yakult Central Institute, Kunitachi-shi, Tokyo, Japan.
Minoru AndoSafety Research Department, Yakult Central Institute, Kunitachi-shi, Tokyo, Japan.
Akinobu KuritaSafety Research Department, Yakult Central Institute, Kunitachi-shi, Tokyo, Japan.
Koji KawakamiSafety Research Department, Yakult Central Institute, Kunitachi-shi, Tokyo, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This study aimed to identify gut microbiota-derived metabolites governing the activity of hepatic CYP3A in blood level. Indole propionic acid (IPA) and lithocholic acid, ligands of the pregnane X receptor, a transcriptional regulator of CYP3A, and various gut microbiota-derived metabolites in blood level were analyzed. Results revealed that IPA and lithocholic acid did not affect CYP3A activity, while indoxyl sulfate (IS), a uremic toxin, affected CYP3A across different cell lines. The effects of IS on primary hepatocytes from three donors were analyzed, and a concentration-dependent impact was observed, as the CYP3A activity decreased in one donor and increased in another. These findings offer initial insights into blood-level gut microbiota-derived metabolites influencing hepatic CYP3A. Furthermore, the study demonstrates that the response to IS, beyond its concentration, can cause variations in hepatic CYP3A activity among individuals. This study advocates accounting for the dual effects of IS and the benefits of personalized medicine.

Indexed as

Cytochrome P-450 CYP3AHepatocytesIndicanLiverGastrointestinal MicrobiomeHumansIndolesLithocholic AcidMalePregnane X ReceptorPropionatesCYP3A protein, humanCytochrome P-450 CYP3AIndicanIndolesLithocholic AcidPregnane X ReceptorPropionates

Identifiers

PMID40638708
PMCPMC12244530

What Socratic holds

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LicenceCC BY
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Registered trials

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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 Socratic graph.