Evidence map›Paper›PMID 36894646›Full record

ArticleScientific reports2023

Decreased Paneth cell α-defensins promote fibrosis in a choline-deficient L-amino acid-defined high-fat diet-induced mouse model of nonalcoholic steatohepatitis via disrupting intestinal microbiota.

Shunta Nakamura, Kiminori Nakamura, Yuki Yokoi, Yu Shimizu, Shuya Ohira, Mizu Hagiwara, Zihao Song, Li Gan, Tomoyasu Aizawa, Daigo Hashimoto and 3 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 11% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Alteration of small intestinal microbiota in diet-induced steatohepatitis mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Small science · 2025
    Article
  9. Article
  10. Article
  11. Review
  12. Review
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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

13 authors at 4 institutions in 2 countries.

Shunta NakamuraGraduate School of Life Science, Hokkaido University, Sapporo, Japan.
Kiminori NakamuraGraduate School of Life Science, Hokkaido University, Sapporo, Japan. kiminori@sci.hokudai.ac.jp.
Yuki YokoiGraduate School of Life Science, Hokkaido University, Sapporo, Japan.
Yu ShimizuDepartment of Cell Biological Science, Faculty of Advanced Life Science, Hokkaido University, Kita-21, Nishi-11, Kita-ku, Sapporo, Hokkaido, 001-0021, Japan.
Shuya OhiraGraduate School of Life Science, Hokkaido University, Sapporo, Japan.
Mizu HagiwaraGraduate School of Life Science, Hokkaido University, Sapporo, Japan.
Zihao SongGraduate School of Life Science, Hokkaido University, Sapporo, Japan.
Li GanGraduate School of Life Science, Hokkaido University, Sapporo, Japan.
Tomoyasu AizawaGraduate School of Life Science, Hokkaido University, Sapporo, Japan.
Daigo HashimotoDepartment of Hematology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
Takanori TeshimaDepartment of Hematology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
Andre J OuelletteDepartment of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Tokiyoshi AyabeGraduate School of Life Science, Hokkaido University, Sapporo, Japan. ayabe@sci.hokudai.ac.jp.
Hokkaido University · JPHokkai Gakuen University · JPNitto (Japan) · JPUniversity of Southern California · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease characterized by fibrosis that develops from fatty liver. Disruption of intestinal microbiota homeostasis, dysbiosis, is associated with fibrosis development in NASH. An antimicrobial peptide α-defensin secreted by Paneth cells in the small intestine is known to regulate composition of the intestinal microbiota. However, involvement of α-defensin in NASH remains unknown. Here, we show that in diet-induced NASH model mice, decrease of fecal α-defensin along with dysbiosis occurs before NASH onset. When α-defensin levels in the intestinal lumen are restored by intravenous administration of R-Spondin1 to induce Paneth cell regeneration or by oral administration of α-defensins, liver fibrosis is ameliorated with dissolving dysbiosis. Furthermore, R-Spondin1 and α-defensin improved liver pathologies together with different features in the intestinal microbiota. These results indicate that decreased α-defensin secretion induces liver fibrosis through dysbiosis, further suggesting Paneth cell α-defensin as a potential therapeutic target for NASH.

Indexed as

alpha-DefensinsGastrointestinal MicrobiomeNon-alcoholic Fatty Liver DiseaseAmino AcidsAnimalsCholineDiet, High-FatDysbiosisLiver CirrhosisMiceMice, Inbred C57BLPaneth Cellsalpha-DefensinsAmino AcidsCholine

Identifiers

PMID36894646
PMCPMC9998432
OpenAlexW4323661943

What OpenQuestion holds

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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 OpenQuestion graph.